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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families
Journal of Clinical Endocrinology and Metabolism, Volume 94, No. 11, Year 2009
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Description
Context and Objective: Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction. Although early diagnosis is important for clinical management, genetic testing is generally performed after the full clinical picture develops. We aimed to identify patients with WRS before any other abnormalities apart from diabetes are present and study the overall frequency of WRS among patients with permanent neonatal diabetes. Research Design and Methods: The coding regions of EIF2AK3 were sequenced in 34 probands with infancy-onset diabetes with a clinical phenotype suggestive of WRS (n = 28) or homozygosity at the WRS locus (n = 6). Results: Twenty-five probands (73.5%) were homozygous or compound heterozygous for mutations in EIF2AK3. Twenty of the 26 mutations identified were novel. Whereas a diagnosis of WRS was suspected before genetic testing in 22 probands, three patients with apparently isolated diabetes were diagnosed after identifying a large homozygous region encompassing EIF2AK3. In contrast to nonconsanguineous pedigrees, mutations in EIF2AK3 are the most common known genetic cause of diabetes among patients born to consanguineous parents (24 vs. < 2%). Age at diabetes onset and birth weight might be used to prioritize genetic testing in the latter group. Conclusions: WRS is the most common cause of permanent neonatal diabetes mellitus in consanguineous pedigrees. In addition to testing patients with a definite clinical diagnosis, EIF2AK3 should be tested in patients with isolated neonatal diabetes diagnosed after 3 wk of age from known consanguineous families, isolated populations, or countries in which inbreeding is frequent. Copyright © 2009 by The Endocrine Society.
Authors & Co-Authors
Rubio-Cabezas, Óscar
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Spain, Madrid
Hospital Infantil Universitario Niño Jesús
Patch, Ann Marie
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Minton, Jayne A.L.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Flanagan, Sarah E.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Edghill, Emma L.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Hussain, Khalid
United Kingdom, London
Great Ormond Street Hospital for Children Nhs Foundation Trust
Balafrej, A.
Morocco, Agdal Rabat
Hôpital D'enfants
Deeb, Asma Al
United Kingdom, London
Imperial College London
Buchanan, C.
United Kingdom, London
King's College Hospital Nhs Foundation Trust
Jefferson, Ian G.
United Arab Emirates, Abu Dhabi
Sheikh Khalifa Medical City
Mutair, Angam
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Hattersley, Andrew T.
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Ellard, Sian
United Kingdom, Plymouth
Peninsula Medical School, Universities of Exeter and Plymouth
Statistics
Citations: 135
Authors: 13
Affiliations: 8
Identifiers
Doi:
10.1210/jc.2009-1137
ISSN:
0021972X
e-ISSN:
0021972X
Research Areas
Genetics And Genomics
Maternal And Child Health
Noncommunicable Diseases