Molecular analysis and long-term clinical evaluation of three siblings with Alstrom syndrome

Abstract

Alstrom syndrome is a rare, autosomal recessive disorder characterized by a wide spectrum of clinical features including early-onset retinal degeneration leading to blindness, sensorineural hearing loss, short stature, obesity, type 2 diabetes, hyperlipidemia and dilated cardiomyopathy. Renal, hepatic and pulmonary dysfunction may occur in the later phases of the disease. The three affected sisters, from a consanguineous Turkish family, with the characteristic features of Alstrom syndrome, were clinically diagnosed in 1987 and followed for 20 years. DNA sequence analysis of ALMS1, the causative gene in Alstrom syndrome, identified a novel homozygous disease-causing mutation, c.8164C > T, resulting in a premature termination codon in exon 10 in each of the three affected sisters. Furthermore, we describe the longitudinal disease progression in this family and report new clinical findings likely associated with Alstrom syndrome, such as pes planus and hyperthyroidism.