Rare compound heterozygous frameshift mutations in ALMS1 gene identified through exome sequencing in a Taiwanese patient with Alström syndrome

Research output: Contribution to journalArticle

Abstract

Alström syndrome (AS) is a rare autosomal recessive disorder that shares clinical features with other ciliopathy-related diseases. Genetic mutation analysis is often required in making differential diagnosis but usually costly in time and effort using conventional Sanger sequencing. Herein we describe a Taiwanese patient presenting cone-rod dystrophy and early-onset obesity that progressed to diabetes mellitus with marked insulin resistance during adolescence. Whole exome sequencing of the patient's genomic DNA identified a novel frameshift mutation in exons 15 (c.10290_10291delTA, p. Lys3431Serfs*10) and a rare mutation in 16 (c.10823_10824delAG, p. Arg3609Alafs*6) of ALMS1 gene. The compound heterozygous mutations were predicted to render truncated proteins. This report highlighted the clinical utility of exome sequencing and extended the knowledge of mutation spectrum in AS patients.

Original languageEnglish
Article number110
JournalFrontiers in Genetics
Volume9
Issue numberAPR
DOIs
Publication statusPublished - 2018 Apr 18

Fingerprint

Exome
Frameshift Mutation
Mutation
Genes
Insulin Resistance
Exons
Diabetes Mellitus
Differential Diagnosis
Obesity
DNA
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Cite this

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title = "Rare compound heterozygous frameshift mutations in ALMS1 gene identified through exome sequencing in a Taiwanese patient with Alstr{\"o}m syndrome",
abstract = "Alstr{\"o}m syndrome (AS) is a rare autosomal recessive disorder that shares clinical features with other ciliopathy-related diseases. Genetic mutation analysis is often required in making differential diagnosis but usually costly in time and effort using conventional Sanger sequencing. Herein we describe a Taiwanese patient presenting cone-rod dystrophy and early-onset obesity that progressed to diabetes mellitus with marked insulin resistance during adolescence. Whole exome sequencing of the patient's genomic DNA identified a novel frameshift mutation in exons 15 (c.10290_10291delTA, p. Lys3431Serfs*10) and a rare mutation in 16 (c.10823_10824delAG, p. Arg3609Alafs*6) of ALMS1 gene. The compound heterozygous mutations were predicted to render truncated proteins. This report highlighted the clinical utility of exome sequencing and extended the knowledge of mutation spectrum in AS patients.",
author = "Meng-Che Tsai and Yu, {Hui Wen} and Tsung-lin Liu and Yen-Yin Chou and Yuan-Yow Chiou and Peng-Chieh Chen",
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T1 - Rare compound heterozygous frameshift mutations in ALMS1 gene identified through exome sequencing in a Taiwanese patient with Alström syndrome

AU - Tsai, Meng-Che

AU - Yu, Hui Wen

AU - Liu, Tsung-lin

AU - Chou, Yen-Yin

AU - Chiou, Yuan-Yow

AU - Chen, Peng-Chieh

PY - 2018/4/18

Y1 - 2018/4/18

N2 - Alström syndrome (AS) is a rare autosomal recessive disorder that shares clinical features with other ciliopathy-related diseases. Genetic mutation analysis is often required in making differential diagnosis but usually costly in time and effort using conventional Sanger sequencing. Herein we describe a Taiwanese patient presenting cone-rod dystrophy and early-onset obesity that progressed to diabetes mellitus with marked insulin resistance during adolescence. Whole exome sequencing of the patient's genomic DNA identified a novel frameshift mutation in exons 15 (c.10290_10291delTA, p. Lys3431Serfs*10) and a rare mutation in 16 (c.10823_10824delAG, p. Arg3609Alafs*6) of ALMS1 gene. The compound heterozygous mutations were predicted to render truncated proteins. This report highlighted the clinical utility of exome sequencing and extended the knowledge of mutation spectrum in AS patients.

AB - Alström syndrome (AS) is a rare autosomal recessive disorder that shares clinical features with other ciliopathy-related diseases. Genetic mutation analysis is often required in making differential diagnosis but usually costly in time and effort using conventional Sanger sequencing. Herein we describe a Taiwanese patient presenting cone-rod dystrophy and early-onset obesity that progressed to diabetes mellitus with marked insulin resistance during adolescence. Whole exome sequencing of the patient's genomic DNA identified a novel frameshift mutation in exons 15 (c.10290_10291delTA, p. Lys3431Serfs*10) and a rare mutation in 16 (c.10823_10824delAG, p. Arg3609Alafs*6) of ALMS1 gene. The compound heterozygous mutations were predicted to render truncated proteins. This report highlighted the clinical utility of exome sequencing and extended the knowledge of mutation spectrum in AS patients.

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