Homozygous loss-of-function mutation in ALMS1 causes the lethal disorder mitogenic cardiomyopathy in two siblings.

ABSTRACT

BACKGROUND: Two siblings from consanguineous parents of Turkish descent presented with isolated dilated cardiomyopathy, leading to early death in infancy. The diagnosis of mitogenic cardiomyopathy was made histologically. METHODS AND RESULTS: Linkage analysis combined with exome sequencing identified a homozygous deleterious mutation in the ALMS1 gene as the cause of this phenotype. CONCLUSIONS: Alström syndrome is characterized by a typically transient dilating cardiomyopathy in infancy, suggesting that mitogenic cardiomyopathy represents the extreme phenotype, resulting in demise before the other clinical symptoms become evident. This observation further illustrates the role of ALMS1 and cell cycle regulation.