Identification of Two Cases of Ciliopathy-Associated Diabetes and Their Mutation Analysis Using Whole Exome Sequencing.
10.4093/dmj.2015.39.5.439
- Author:
Min Kyeong KIM
1
;
Soo Heon KWAK
;
Shinae KANG
;
Hye Seung JUNG
;
Young Min CHO
;
Seong Yeon KIM
;
Kyong Soo PARK
Author Information
1. Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. kspark@snu.ac.kr
- Publication Type:Brief Communication
- Keywords:
ALMS1;
Alstrom syndrome;
Bardet-Biedl syndrome;
BBS1;
Ciliopathy;
Diabetes mellitus;
Next generation sequencing;
Sanger sequencing;
Whole exome sequencing
- MeSH:
Alstrom Syndrome;
Bardet-Biedl Syndrome;
Blindness;
Codon, Nonsense;
Diabetes Mellitus;
Exome*;
Exons;
Female;
Frameshift Mutation;
Genotype;
Hearing Loss;
Humans;
Insulin Resistance;
Korea;
Obesity;
Obesity, Morbid;
Polydactyly;
Young Adult
- From:Diabetes & Metabolism Journal
2015;39(5):439-443
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
