{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:11:46Z","timestamp":1773724306583,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T00:00:00Z","timestamp":1510012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agence Nationale pour la Recherche","award":["ANR-09-GENO-021"],"award-info":[{"award-number":["ANR-09-GENO-021"]}]},{"name":"the European Foundation for the Study of Diabetes (EFSD)\/Juvenile Diabetes Research Foundation (JDRF)\/NOVO Nordisk"},{"DOI":"10.13039\/501100009820","name":"Assistance Publique-H\u00f4pitaux de Paris","doi-asserted-by":"publisher","award":["Programme Hospitalier de Recherche Clinique DIAGENE"],"award-info":[{"award-number":["Programme Hospitalier de Recherche Clinique DIAGENE"]}],"id":[{"id":"10.13039\/501100009820","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation maladies rares in the frame of the program \u201cHigh throughput sequencing and rare disease\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Monogenic forms of diabetes may account for 1\u20135% of all cases of diabetes, and may occur in the context of syndromic presentations. We investigated the case of a girl affected by insulin-dependent diabetes, diagnosed at 6 years old, associated with congenital cataract. Her consanguineous parents and her four other siblings did not have diabetes or cataract, suggesting a recessive syndrome. Using whole exome sequencing of the affected proband, we identified a heterozygous p.R825Q ABCC8 mutation, located at the exact same amino-acid position as the p.R825W recurring diabetes mutation, hence likely responsible for the diabetes condition, and a homozygous p.G71S mutation in CRYBB1, a gene known to be responsible for congenital cataract. Both mutations were predicted to be damaging and were absent or extremely rare in public databases. Unexpectedly, we found that the mother was also homozygous for the CRYBB1 mutation, and both the mother and one unaffected sibling were heterozygous for the ABCC8 mutation, suggesting incomplete penetrance of both mutations. Incomplete penetrance of ABCC8 mutations is well documented, but this is the first report of an incomplete penetrance of a CRYBB1 mutation, manifesting between susceptible subjects (unaffected mother vs. affected child) and to some extent within the patient herself, who had distinct cataract severities in both eyes. Our finding illustrates the importance of family studies to unmask the role of confounding factors such as double-gene mutations and incomplete penetrance that may mimic monogenic syndromes including in the case of strongly evocative family structure with consanguinity.<\/jats:p>","DOI":"10.3390\/genes8110309","type":"journal-article","created":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T11:46:01Z","timestamp":1510055161000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Juvenile-Onset Diabetes and Congenital Cataract: \u201cDouble-Gene\u201d Mutations Mimicking a Syndromic Diabetes Presentation"],"prefix":"10.3390","volume":"8","author":[{"given":"Caroline","family":"Lenfant","sequence":"first","affiliation":[{"name":"INSERM UMR-S 958, Facult\u00e9 de M\u00e9decine Paris Diderot, University Paris 7 Denis-Diderot, Sorbonne Paris Cit\u00e9, Paris 75010, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Baz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, H\u00f4tel Dieu Hospital, Beirut 166830, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Degavre","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 958, Facult\u00e9 de M\u00e9decine Paris Diderot, University Paris 7 Denis-Diderot, Sorbonne Paris Cit\u00e9, Paris 75010, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Philippi","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 958, Facult\u00e9 de M\u00e9decine Paris Diderot, University Paris 7 Denis-Diderot, Sorbonne Paris Cit\u00e9, Paris 75010, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Sen\u00e9e","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 958, Facult\u00e9 de M\u00e9decine Paris Diderot, University Paris 7 Denis-Diderot, Sorbonne Paris Cit\u00e9, Paris 75010, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Vandiedonck","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 958, Facult\u00e9 de M\u00e9decine Paris Diderot, University Paris 7 Denis-Diderot, Sorbonne Paris Cit\u00e9, Paris 75010, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9line","family":"Derbois","sequence":"additional","affiliation":[{"name":"Centre National de Recherche en G\u00e9nomique Humaine, Institut de Biologie Fran\u00e7ois Jacob, Commissariat \u00e0 l\u2019Energie Atomique, Evry 91057, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Nicolino","sequence":"additional","affiliation":[{"name":"H\u00f4pital Femme-M\u00e8re-Enfant, Division of Pediatric Endocrinology, Hospices Civils de Lyon, Universit\u00e9 Lyon 1, Bron cedex 69677, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Zalloua","sequence":"additional","affiliation":[{"name":"School of Medicine, Lebanese American University, Beirut 1102 2801, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Julier","sequence":"additional","affiliation":[{"name":"INSERM UMR-S 958, Facult\u00e9 de M\u00e9decine Paris Diderot, University Paris 7 Denis-Diderot, Sorbonne Paris Cit\u00e9, Paris 75010, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/ncpendmet0778","article-title":"Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes","volume":"4","author":"Murphy","year":"2008","journal-title":"Nat. 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