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Yang Li, ZHE PAN, BING DONG, XIAOHUI ZHANG; Large Novel ALMS1 Gene Deletion Detected In Chinese Families With AlströM Syndrome. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1570. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Alström syndrome (OMIM: 203800) is a rare and severe autosomal recessive disorder with five clinical features including atypical retinal pigmentary degeneration, sensorineural hearing loss, obesity, type II diabetes mellitus, and normal mentation(1). The single disease causing gene is the ALMS1 gene located in the chromosome 2 p13.1. The current study described the clinical and genetic findings in two Chinese families with Alström syndrome.
Two unrelated families were examined clinically. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Exon 8, 10, 16 of the ALMS1 gene was amplified by polymerase chain reaction (PCR). The PCR products were analyzed using direct sequencing. Large deletion was analyzed by real-time quantitative PCR (RQ-PCR) using all 23 exons primers of the ALMS1 gene. Long-range PCR followed by DNA sequencing was used to define the breakpoints.
By clinical examination and laboratory investigations, three individuals from the two families were diagnosed of Alström syndrome. All patients presented congenital progressive atypical retinal pigmentary degeneration, sensorineural deafness, infantile onset obesity, diabetic, hepatic and renal dysfunction, and normal intelligence. Sequencing of part of the ALMS1 gene identified two novel heterozygous small deletions: c. 4145delACTC (p. S1383FS) in family F1 and c.9460delG (p. V3154X) in family F2, one novle heterozygous insert mutation c.9452insAATA (p.S3151fs) in family F2. A 199.3kb large deletion, which encompassed exon 3-23 of the ALMS1 gene, was identified in family F1. All novel mutations were co-segregated with the phenotype of the two families, but were not found in 100 normal controls.
A large deletion was first identified in the ALMS1 gene; the ALMS1 gene mutation screen can provide the genetic counseling for the families of Alström syndrome and is important for the diagnosis of the cases with atypical clinical features.
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