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Eur J Hum Genet. 2016 Aug;24(8):1223-7. doi: 10.1038/ejhg.2015.260. Epub 2015 Dec 23.

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

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  • 1Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
  • 2Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • 3Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Pakistan.
  • 4Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
  • 5Department of Biotechnology, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan.
  • 6Department of Genome Sciences, University of Washington, Seattle, WA, USA.


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.

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