{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T03:17:42Z","timestamp":1764645462324},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,11]]},"abstract":"\nBackground<\/jats:title>\nIGF1 is a key factor in fetal and postnatal growth. To date, only three homozygous IGF1<\/jats:italic> gene defects leading to complete or partial loss of IGF1 activity have been reported in three short patients born small for gestational age. We describe the fourth patient with severe short stature presenting a novel homozygous IGF1<\/jats:italic> gene mutation.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nWe report a boy born from consanguineous parents at 40 weeks of gestational age with intrauterine growth restriction and severe postnatal growth failure. Physical examination revealed proportionate short stature, microcephaly, facial dysmorphism, bilateral sensorineural deafness and mild global developmental delay. Basal growth hormone (GH) fluctuated from 0.2 to 29\u2009ng\/mL, while IGF1 levels ranged from \u22121.15 to 2.95 SDS. IGFBP3 was normal-high. SNP array delimited chromosomal regions of homozygosity, including 12q23.2 where IGF1<\/jats:italic> is located. IGF1<\/jats:italic> screening by HRM revealed a homozygous missense variant NM_000618.4(IGF1):c.322T>C, p.(Tyr108His). The change of the highly conserved Tyr60 in the mature IGF1 peptide was consistently predicted as pathogenic by multiple bioinformatic tools. Tyr60 has been described to be critical for IGF1 interaction with type 1 IGF receptor (IGF1R). In vitro<\/jats:italic>, HEK293T cells showed a marked reduction of IGF1R phosphorylation after stimulation with serum from the patient as compared to sera from age-matched controls. Mutant IGF1 was also less efficient in inducing cell growth.<\/jats:p>\n<\/jats:sec>\n\nConclusion<\/jats:title>\nThe present report broadens the spectrum of clinical and biochemical presentation of homozygous IGF1<\/jats:italic> defects and underscores the variability these patients may present depending on the IGF\/IGF1R pathway activity.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-19-0563","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T10:36:30Z","timestamp":1568975790000},"page":"K43-K53","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":18,"title":["A homozygous mutation in the highly conserved Tyr60 of the mature IGF1 peptide broadens the spectrum of IGF1 deficiency"],"prefix":"10.1093","volume":"181","author":[{"given":"Ana Claudia","family":"Keselman","sequence":"first","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayelen","family":"Martin","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula Alejandra","family":"Scaglia","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora Mar\u00eda","family":"Sanguineti","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Armando","sequence":"additional","affiliation":[{"name":"2Servicio de Gen\u00e9tica, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e9bora","family":"Braslavsky","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Gabriela","family":"Ballerini","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Gabriela","family":"Ropelato","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Ramirez","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estefan\u00eda","family":"Landi","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina","family":"Domen\u00e9","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia F","family":"Castro","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) CONICET \u2013 FEI \u2013 Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamilton","family":"Cassinelli","sequence":"additional","affiliation":[{"name":"1Centro de Investigaciones Endocrinol\u00f3gicas \u2018Dr. C\u00e9sar Bergad\u00e1\u2019 (CEDIE) 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