title: Congenital posterior pole cataract and adult onset dilating cardiomyopathy: expanding the phenotype of αB-crystallinopathies.
abstract: Mutations in the αB-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 αB-crystallin protein with 19 amino acid residues. Affected family members combine a CPPC with an adult onset dilated cardiomyopathy (DCM), thereby expanding the αB-crystallinopathy phenotype. Repolarisation 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 αB-crystallinopathies.
authors.affiliation: Department of Medical Genetics.
authors.forename: J J
authors.initials: JJ
authors.lastname: van der Smagt
authors.forename: A
authors.initials: A
authors.lastname: Vink
authors.forename: J H
authors.initials: JH
authors.lastname: Kirkels
authors.forename: M
authors.initials: M
authors.lastname: Nelen
authors.forename: H
authors.initials: H
authors.lastname: ter Heide
authors.forename: M M C
authors.initials: MM
authors.lastname: Molenschot
authors.forename: R A
authors.initials: RA
authors.lastname: Weger
authors.forename: P A W
authors.initials: PA
authors.lastname: Schellekens
authors.forename: J
authors.initials: J
authors.lastname: Hoogendijk
authors.forename: D
authors.initials: D
authors.lastname: Dooijes
mesh_terms: D000328:Adult; D017668:Age of Onset; D002311:Cardiomyopathy, Dilated / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D010375:Pedigree; D038203:alpha-Crystallin B Chain / Q000235:genetics* / Q000378:metabolism
chemical_list: C059215:CRYAB protein, human; D038203:alpha-Crystallin B Chain
keywords: cardiomyopathy; cataract; congenital; crystallins; desmin-related myopathies; dilated