Expansion of the spectrum of ITGB6-related disorders to adolescent alopecia, dentogingival abnormalities and intellectual disability.

TitleExpansion of the spectrum of ITGB6-related disorders to adolescent alopecia, dentogingival abnormalities and intellectual disability.
Publication TypeJournal Article
Year of Publication2016
AuthorsAnsar, 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 AuthorsUniversity of Washington Center for Mendelian Genomics
JournalEur J Hum Genet
Volume24
Issue8
Pagination1223-7
Date Published2016 Aug
ISSN1476-5438
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.

DOI10.1038/ejhg.2015.260
Alternate JournalEur. J. Hum. Genet.
PubMed ID26695873
PubMed Central IDPMC4970676
Grant ListU54 HG006493 / HG / NHGRI NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States