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

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.