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The variant spectrum and associated molecular mechanisms underlying phenotypic variability and disease severity remain incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated 45 newly identified individuals carrying 33 distinct\n                      <jats:italic>AGO2<\/jats:italic>\n                      variants, 30 of which were previously unreported. Phenotypic data from these and previously reported cases (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200970) were integrated to delineate the LESKRES-associated clinical spectrum and genotype\u2013phenotype correlations. Functional studies included shRNA-based silencing, co-immunoprecipitation, subcellular localization, and sequencing of AGO2-bound miRNAs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All individuals presented with a neurodevelopmental disorder of variable severity. Delayed speech and language development (97%), intellectual disability (97%), and motor delay (93%) were the most consistent features, frequently accompanied by muscular hypotonia, autistic traits, attention deficit hyperactivity disorder, visual impairment and structural brain anomalies. Systemic manifestations, including skeletal, craniofacial, cardiac, and male urogenital anomalies were common, underscoring AGO2\u2019s multisystemic role. Moreover, we report occurrence of gonadal mosaicism and reveal the presence of interfamilial and variant-specific clinical heterogeneity. Variants clustered in defined regions of AGO2, including the L1 loop, helix-7, and multiple loops of the PIWI domain, highlight structural hotspots critical for RISC activity. Not all pathogenic variants impaired shRNA-mediated silencing; this was restricted to p.(Arg714Trp) and p.(Asn729His). Biochemical analyses revealed that p.(Asp619Asn) impaired GW182 binding and P-body assembly. Variants p.(Arg506Gln), p.(Glu531Gln) p.(Gly604Arg) and p.(Asp619Asn), reduced C-terminal phosphorylation, implicating defective AGO2 recycling. AGO2\u2013miRNA co-immunoprecipitation and sequencing demonstrated variant-specific perturbations in miRNA association, strand selectivity, and isomiR generation. Variants near the hinge of the helix-7 region, especially p.(Phe182del), induced extensive changes in miRNA association and 3\u2032-end modification, suggesting impaired anchoring within the miRNA-binding pocket.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings substantially broaden the clinical and molecular landscape of LESKRES, establishing AGO2 as a pivotal regulator of neurodevelopment whose structural integrity is essential for precise miRNA-mediated gene regulation. Pathogenic variants disrupt distinct interconnected processes: P-body association, phosphorylation-dependent turnover, and miRNA interactions, culminating in dysregulated post-transcriptional gene silencing. These mechanistic insights link specific structural perturbations in AGO2 to graded clinical outcomes and underscore the critical role of AGO2 conformational dynamics in human neurodevelopment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13073-026-01745-4","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:04:28Z","timestamp":1787371468000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The clinical and molecular spectrum of AGO2-associated Lessel-Kreienkamp neurodevelopmental syndrome"],"prefix":"10.1186","volume":"18","author":[{"given":"Debora","family":"Tibbe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Kiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olena","family":"Ielesicheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Robles de Maruri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helia","family":"Mahboobi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joschka","family":"Z\u00fcghart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Hinrich","family":"H\u00f6nck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Meier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Biasella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Leg\u00fce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Francisca","family":"Lopez Avaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Blair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Lester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benito","family":"Banos-Pinero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose S.","family":"Pulido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Procopio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Quelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey J.","family":"Leal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian A.","family":"Martinez-Agosto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Bottomley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1gnes","family":"Till","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Hadzsiev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Szalai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn Nicole","family":"Weaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Fluss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Margot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Almoguera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Lorda-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"L\u00f3pez-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080205."},{"key":"1745_CR57","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1079A>G; p.(Gln360Arg). Variant #0001080206. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080206."},{"key":"1745_CR58","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1092G>A; p.(Met364Ile). Variant #0001080207. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080207."},{"key":"1745_CR59","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1093A>C; p.(Ile365Val). Variant #0001080208. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080208."},{"key":"1745_CR60","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1094T>A; p.(Ile365Asn). Variant #0001080210. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080210."},{"key":"1745_CR61","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1094T>A; p.(Ala372Glu). Variant #0001080211. https:\/\/databases.lovd.nl\/shared\/variants\/0001080211."},{"key":"1745_CR62","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1244C>T; p.(Pro415Leu). Variant #0001080212. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080212."},{"key":"1745_CR63","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1303T>C; p.(Trp435Arg). Variant #0001080213. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080213."},{"key":"1745_CR64","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1517G>A; p.(Arg506Gln). Variant #0001080214. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080214."},{"key":"1745_CR65","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1591G>C; p.(Glu531Gln). Variant #0001080215. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080215."},{"key":"1745_CR66","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1631C>T; p.(Thr544Met). Variant #0001080216. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080216."},{"key":"1745_CR67","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1805C>A; p.(Pro602His). Variant #0001080217. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080217."},{"key":"1745_CR68","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1805C>G; p.(Pro602Arg). Variant #0001080218. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080218."},{"key":"1745_CR69","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1810G>A; p.(Gly604Arg). Variant #0001080223. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080223."},{"key":"1745_CR70","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.1855G>A; p.(Asp619Asn). Variant #0001080224. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080224."},{"key":"1745_CR71","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.2140C>T; p.(Arg714Trp). Variant #0001080226. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080226."},{"key":"1745_CR72","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.2140C>T; p.(Asn729His). Variant #0001080227. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080227."},{"key":"1745_CR73","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.2273G>A; p.(Gly758Glu). Variant #0001080228. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080228."},{"key":"1745_CR74","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.2281A>T; p.(Arg761Trp). Variant #0001080229. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080229."},{"key":"1745_CR75","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.2348C>T; p.(Thr783Ile). Variant #0001080231. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080231."},{"key":"1745_CR76","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.2375G>A; p.(Arg792His). Variant #0001080232. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080232."},{"key":"1745_CR77","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.2383C>T; p.(Arg795Cys). Variant #0001080234. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080234."},{"key":"1745_CR78","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.2402C>T; p.(Ala801Val). Variant #0001080235. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080235."},{"key":"1745_CR79","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.2435G>A; p.(Arg812Gln). Variant #0001080236. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080236."},{"key":"1745_CR80","unstructured":"Tibbe, D, Kiel C, Ielesicheva O, Robles de Maruri K, Mahboobi H, Z\u00fcghart J, H\u00f6nck H-H, Meier C, Biasella F, Leg\u00fce M, Lopez Avaria MF, Blair E, Lester T, Banos-Pinero B, Pulido JS, Schneider A, Procopio R, Quelin C, Leal BJ, Martinez-Agosto JA, Bottomley SA, Till A, Hadzsiev K, Szalai R, Weaver KN, Fluss J, Margot H, Almoguera B, Lorda-S\u00e1nchez I, L\u00f3pez-L\u00f3pez L, Hamm JA, Goel H, Alanay Y, Akgun Do\u011fan O, Ozkose-Iyigel GS, Baujat G, Lesieur-Sebellin M, Rondeau S, Schon K, Christopher J, Isidor B, Cogne B, Agrawal NS, Dahlhauser R, Furuta Y, Rabin R, Pappas J, Patel C, J\u00e4rvel\u00e4 I, Rauhala M, Schrauwen I, Leal SM, Banka S, Tharakan R, Pebrel-Richard C, Laffargue F, Durand N, Celse T, Hempel M, Valentin I, Gregorova A, Noskova L, Baumgartner S, \u00dcberbacher C, Muru K, Murumets \u00dc, Lilles S, Steindl K, Rauch A, Ruscitti F, Verloes A, Levy J, Park J, Haack TB, Bader I, Julia S, Banneau G, Muir AM, Lessel D, Kreienkamp HJ. NM_012154.3 (AGO2) c.519\u201324_529del; p.?. Variant #0001080237. LOVD 3.0. https:\/\/databases.lovd.nl\/shared\/variants\/0001080237."}],"container-title":["Genome Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13073-026-01745-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01745-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01745-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:08:15Z","timestamp":1787566095000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13073-026-01745-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":80,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1745"],"URL":"https:\/\/doi.org\/10.1186\/s13073-026-01745-4","relation":{},"ISSN":["1756-994X"],"issn-type":[{"value":"1756-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]},"assertion":[{"value":"16 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The research described in this manuscript conformed to the principles of the Helsinki Declaration. Written informed consent for all subjects was obtained in accordance with protocols approved by the respective ethics committees of the institutions involved (approval number by the Ethics Committee of the Hamburg Chamber of Physicians: PV 3802). All animal experiments were approved by, and conducted in accordance with, the guidelines of the Animal Welfare Committee of the University Medical Center (Hamburg, Germany) under permission number Org1018.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent for publication was obtained for all subjects.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"AMM is an employee of and may own stock in GeneDx. The other authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"125"}}