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

• Published in: Clinical genetics Vol. 72; no. 4; pp. 351 - 356
• Main Authors: Özgül, RK, Satman, I, Collin, GB, Hinman, EG, Marshall, JD, Kocaman, O, Tütüncü, Y, Yılmaz, T, Naggert, JK
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2007; Blackwell
• Subjects: Adolescent; Adult; ALMS1; Alström syndrome; Biological and medical sciences; Blindness - diagnosis; Blindness - genetics; Cardiomyopathy, Dilated - diagnosis; Cardiomyopathy, Dilated - genetics; Child; diabetes mellitus; Diabetes. Impaired glucose tolerance; DNA Mutational Analysis; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Family Health; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes, Recessive; Genetics of eukaryotes. Biological and molecular evolution; hearing loss; Hearing Loss, Sensorineural - diagnosis; Hearing Loss, Sensorineural - genetics; Homozygote; Humans; Medical genetics; Medical sciences; Molecular and cellular biology; Proteins - genetics; Sequence Analysis, DNA; Syndrome; Endocrinopathy; Human; Evaluation; Family study; Diabetes mellitus; Alström syndrome; Auditory disorder; Sibling; Long term; Syndrome; Hearing loss; ALMS1; ENT disease; Genetics; Molecular biology
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2007.00848.x

Alström 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 Alström syndrome, were clinically diagnosed in 1987 and followed for 20 years. DNA sequence analysis of ALMS1, the causative gene in Alström 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 Alström syndrome, such as pes planus and hyperthyroidism.