Congenital posterior pole cataract and adult onset dilating cardiomyopathy: expanding the phenotype of [alpha]B-crystallinopathies

• Published in: Clinical genetics 2014-04, Vol.85 (4), p.381
• Main Authors: van der Smagt, JJ, Vink, A, Kirkels, JH, Nelen, M, ter Heide, H, Molenschot, MMC, Weger, RA, Schellekens, PAW, Hoogendijk, J, Dooijes, D
• Format: Article
• Language: English
• Subjects: Cardiomyopathy; Cataracts; Congenital diseases; Families & family life; Genes; Mutation
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.12169

Mutations in the [alpha]B-crystallin gene (CRYAB) have been reported in desmin-related myopathies, with or without cardiac involvement. Mutations in this gene have also been documented in large multi-generation families with autosomal dominant congenital posterior pole cataract (CPPC). In these congenital cataract families no cardiac or muscular phenotype was reported. This report describes a family with an unusual read-through mutation in CRYAB, leading to the elongation of the normal [alpha]B-crystallin protein with 19 amino acid residues. Affected family members combine a CPPC with an adult onset dilated cardiomyopathy (DCM), thereby expanding the [alpha]B-crystallinopathy phenotype. Repolarization abnormalities preceded the onset of cardiomyopathy and were already present in childhood. No skeletal myopathy was observed. This report illustrates that congenital cataract can be a prelude to more severe disease even outside the context of inborn errors of metabolism. The identification of a CRYAB mutation in this family supports the notion that mutations in this gene are a rare cause of genetically determined DCM. The combined congenital cataract/cardiomyopathy phenotype adds to our understanding of the complex phenotypic spectrum of [alpha]B-crystallinopathies.[PUBLICATION ABSTRACT]