Title | Expansion of the spectrum of ITGB6-related disorders to adolescent alopecia, dentogingival abnormalities and intellectual disability. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Ansar, M, Jan, A, Santos-Cortez, RLyn P, Wang, X, Suliman, M, Acharya, A, Habib, R, Abbe, I, Ali, G, Lee, K, Smith, JD, Nickerson, DA, Shendure, J, Bamshad, MJ, Ahmad, W, Leal, SM |
Corporate Authors | University of Washington Center for Mendelian Genomics |
Journal | Eur J Hum Genet |
Volume | 24 |
Issue | 8 |
Pagination | 1223-7 |
Date Published | 2016 08 |
ISSN | 1476-5438 |
Keywords | Adolescent, Adult, Alopecia, Child, Female, Humans, Integrin beta Chains, Intellectual Disability, Male, Mutation, Missense, Pedigree, Phenotype, Protein Domains, Syndrome, Tooth Abnormalities |
Abstract | Alopecia with mental retardation (APMR) is a very rare disorder. In this study, we report on a consanguineous Pakistani family (AP91) with mild-to-moderate intellectual disability, adolescent alopecia and dentogingival abnormalities. Using homozygosity mapping, linkage analysis and exome sequencing, we identified a novel rare missense variant c.898G>A (p.(Glu300Lys)) in ITGB6, which co-segregates with the phenotype within the family and is predicted to be deleterious. Structural modeling shows that Glu300 lies in the β-propeller domain, and is surrounded by several residues that are important for heterodimerization with α integrin. Previous studies showed that ITGB6 variants can cause amelogenesis imperfecta in humans, but patients from family AP91 who are homozygous for the c.898G>A variant present with neurological and dermatological features, indicating a role for ITGB6 beyond enamel formation. Our study demonstrates that a rare deleterious variant within ITGB6 causes not only dentogingival anomalies but also intellectual disability and alopecia. |
DOI | 10.1038/ejhg.2015.260 |
Alternate Journal | Eur. J. Hum. Genet. |
PubMed ID | 26695873 |
PubMed Central ID | PMC4970676 |
Grant List | U54 HG006493 / HG / NHGRI NIH HHS / United States UM1 HG006493 / HG / NHGRI NIH HHS / United States |