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KMID : 1200020150390050439
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Diabetes & Metabolism Journal
2015 Volume.39 No. 5 p.439 ~ p.443
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Identification of Two Cases of Ciliopathy-Associated Diabetes and Their Mutation Analysis Using Whole Exome Sequencing
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:Kim Min-Kyeong
:Kwak Soo-Heon/:Kang Shin-Ae/:Jung Hye-Seung/:Cho Young-Min/:Kim Seong-Yeon/:Park Kyong-Soo
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Abstract
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Background: Alstrom syndrome and Bardet-Biedl syndrome are autosomal recessively inherited ciliopathies with common characteristics of obesity, diabetes, and blindness. Alstrom syndrome is caused by a mutation in the ALMS1 gene, and Bardet-Biedl syndrome is caused by mutations in BBS1-16 genes. Herein we report genetically confirmed cases of Alstrom syndrome and Bardet-Biedl syndrome in Korea using whole exome sequencing.
Methods: Exome capture was done using SureSelect Human All Exon Kit V4+UTRs (Agilent Technologies). HiSeq2000 system (Illumina) was used for massive parallel sequencing. Sanger sequencing was used for genotype confirmation and familial cosegregation analysis.
Results: A 21-year old Korean woman was clinically diagnosed with Alstrom syndrome. She had diabetes, blindness, obesity, severe insulin resistance, and hearing loss. Whole exome sequencing revealed a nonsense mutation in exon 10 of ALMS1 (c.8776C>T, p.R2926X) and a seven base-pair deletion resulting in frameshift mutation in exon 8 (c.6410_6416del, p.2137_2139del). A 24-year-old Korean man had Bardet-Biedl syndrome with diabetes, blindness, obesity, and a history of polydactyly. Whole exome sequencing revealed a nonsynonymous mutation in exon 11 of the BBS1 gene (c.1061A>G, p.E354G) and mutation at the normal splicing recognition site of exon 7 of the BBS1 gene (c.519-1G>T).
Conclusion: We found novel compound heterozygous mutations of Alstrom syndrome and Bardet-Biedl syndrome using whole exome sequencing. The whole exome sequencing successfully identified novel genetic variants of ciliopathy-associated diabetes.
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KEYWORD
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ALMS1, Alstrom syndrome, Bardet-Biedl syndrome, BBS1, Ciliopathy, Diabetes mellitus, Next generation sequencing, Sanger sequencing, Whole exome sequencing
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