Identification of Two Cases of Ciliopathy-Associated Diabetes and Their Mutation Analysis Using Whole Exome Sequencing
Diabetes & Metabolism Journal
;
: 439-443, 2015.
Article
in English
| WPRIM
| ID: wpr-165652
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Obesity, Morbid
/
Insulin Resistance
/
Blindness
/
Exons
/
Frameshift Mutation
/
Polydactyly
/
Codon, Nonsense
/
Bardet-Biedl Syndrome
/
Diabetes Mellitus
/
Alstrom Syndrome
Type of study:
Diagnostic study
/
Prognostic study
Limits:
Female
/
Humans
Country/Region as subject:
Asia
Language:
English
Journal:
Diabetes & Metabolism Journal
Year:
2015
Type:
Article
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