{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T01:19:40Z","timestamp":1771636780725,"version":"3.50.1"},"reference-count":20,"publisher":"BMJ","issue":"11","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,7,11]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>\n                    11\u03b2-hydroxylase deficiency (11\u03b2OHD) is the second most common cause (5%) of congenital adrenal hyperplasia (CAH). The\n                    <jats:italic>CYP11B1<\/jats:italic>\n                    gene shares 95% of genomic sequence homology with\n                    <jats:italic>CYP11B2,<\/jats:italic>\n                    and therefore Sanger sequencing remains the gold standard. We present a case of 11\u03b2OHD due to an intragenic inversion in\n                    <jats:italic>CYP11B1<\/jats:italic>\n                    that was missed by both the Sanger sequencing and massive parallel sequencing (MPS) methods. The child was born with virilised genitalia at Prader stage 4 and the biological findings showed a hydromineral retention pattern and a pathognomonic increase in steroid precursors suggestive of 11\u03b2OHD. Standard trio analysis revealed only one heterozygous pathogenic variation inherited from the father. The study using MPS showed similar outcomes. Careful observation of the alignment BAM files revealed breaks in sequencing depth, incomplete alignments and systematic paradoxical read-pairs orientation. A specifically designed amplification and Sanger protocol confirmed the novel NM_000497.4(\n                    <jats:italic>CYP11B1<\/jats:italic>\n                    ):c.[892_1121+7\u2009inv;1121+8_1121+9del]; p.(Glu298HisfsTer113) variant at heterozygous state in the proband and his mother, fulfilling the diagnosis. The present case reports the first short intragenic inversion in CAH and illustrates the pitfalls that must always be kept in mind when using sequencing methods. When the phenotype is unequivocal, a thorough investigation of the locus should be carried out with cross-use of different techniques.\n                  <\/jats:p>","DOI":"10.1136\/jmg-2025-110880","type":"journal-article","created":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T22:15:19Z","timestamp":1755468919000},"page":"734-738","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["First intragenic inversion of\n                    <i>CYP11B1<\/i>\n                    gene causing 11\u03b2-hydroxylase deficiency: a molecular diagnosis easily overlooked"],"prefix":"10.1136","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9336-6874","authenticated-orcid":false,"given":"Cl\u00e9ment","family":"Janot","sequence":"first","affiliation":[{"name":"LBMMS, Service de Biochimie et Biologie mol\u00e9culaire, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, Auvergne-Rh\u00f4ne-Alpes, France"},{"name":"Stem-Cell and Brain Research Institute (SBRI), Inserm U1208, Universit\u00e9 Claude Bernard Lyon 1, Bron, Auvergne-Rh\u00f4ne-Alpes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9888-6768","authenticated-orcid":false,"given":"Kahina","family":"Mohammedi","sequence":"additional","affiliation":[{"name":"University of Health Sciences Algiers, Algiers, Algeria"},{"name":"Department of Pediatrics, Etablissement Public Hospitalier Ain Taya, Algiers, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2130-9097","authenticated-orcid":false,"given":"Delphine","family":"Mallet","sequence":"additional","affiliation":[{"name":"LBMMS, Service de Biochimie et Biologie mol\u00e9culaire, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, Auvergne-Rh\u00f4ne-Alpes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e9vin","family":"Choron","sequence":"additional","affiliation":[{"name":"LBMMS, Service de Biochimie et Biologie mol\u00e9culaire, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, Auvergne-Rh\u00f4ne-Alpes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Plotton","sequence":"additional","affiliation":[{"name":"LBMMS, Service de Biochimie et Biologie mol\u00e9culaire, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, Auvergne-Rh\u00f4ne-Alpes, France"},{"name":"Stem-Cell and Brain Research Institute (SBRI), Inserm U1208, Universit\u00e9 Claude Bernard Lyon 1, Bron, Auvergne-Rh\u00f4ne-Alpes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9681-4062","authenticated-orcid":false,"given":"Jordan","family":"Teoli","sequence":"additional","affiliation":[{"name":"LBMMS, Service de Biochimie et Biologie mol\u00e9culaire, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, Auvergne-Rh\u00f4ne-Alpes, France"},{"name":"Stem-Cell and Brain Research Institute (SBRI), Inserm U1208, Universit\u00e9 Claude Bernard Lyon 1, Bron, Auvergne-Rh\u00f4ne-Alpes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmahane","family":"Ladjouze","sequence":"additional","affiliation":[{"name":"University of Health Sciences Algiers, Algiers, Algeria"},{"name":"Department of Pediatrics A, CHU B\u00e9ni-Messous, Algiers, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8078-4746","authenticated-orcid":false,"given":"Florence","family":"Roucher-Boulez","sequence":"additional","affiliation":[{"name":"LBMMS, Service de Biochimie et Biologie mol\u00e9culaire, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, Auvergne-Rh\u00f4ne-Alpes, France"},{"name":"Stem-Cell and Brain 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