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Congenital posterior pole cataract and adult onset dilating cardiomyopathy: expanding the phenotype of αB‐crystallinopathies
Author(s) -
van der Smagt J.J.,
Vink A.,
Kirkels J.H.,
Nelen M.,
ter Heide H.,
Molenschot M.M.C.,
Weger R.A.,
Schellekens P.A.W.,
Hoogendijk J.,
Dooijes D.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12169
Subject(s) - phenotype , cardiomyopathy , medicine , dilated cardiomyopathy , mutation , genetics , context (archaeology) , myopathy , gene , biology , heart failure , paleontology
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.