Expansion of the Spectrum of ITGB6-Related Disorders to Adolescent Alopecia, Dentogingival Abnormalities, and Intellectual Disability

December 2015 in “ European Journal of Human Genetics ”

Muhammad Ansar, Abid Jan, Suzanne M. Leal, Xin Wang, Muhammad Suliman, Anushree Acharya, Rabia Habib, Izoduwa Abbe, Ghazanfar Ali, Kwanghyuk Lee, Joshua D. Smith, Deborah A. Nickerson, Jay Shendure, Michael J. Bamshad, Wasim Ahmad, Suzanne M. Leal

ITGB6 adolescent alopecia dentogingival abnormalities intellectual disability homozygosity mapping linkage analysis exome sequencing missense variant heterodimerization α integrin amelogenesis imperfecta alopecia hair loss genetic mapping genetic sequencing

TLDR A rare ITGB6 gene variant causes intellectual disability, hair loss, and dental issues.

This study reported on a consanguineous Pakistani family with mild-to-moderate intellectual disability, adolescent alopecia, and dentogingival abnormalities. Using homozygosity mapping, linkage analysis, and exome sequencing, researchers identified a novel missense variant c.898G>A (p.(Glu300Lys)) in ITGB6, which co-segregated with the phenotype and was predicted to be deleterious. Structural modeling indicated that Glu300 is crucial for heterodimerization with α integrin. While previous studies linked ITGB6 variants to amelogenesis imperfecta, this study expanded the spectrum of ITGB6-related disorders to include neurological and dermatological features, demonstrating that a rare deleterious variant in ITGB6 causes not only dentogingival anomalies but also intellectual disability and alopecia.

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