摘要

PURPOSE: Schwannomatosis, a subtype of neurofibromatosis, is characterized by multiple benign, nonvestibular, nonintradermal schwannomas. Although the tumor suppressor SMARCB1 gene has been frequently identified as the underlying genetic cause of half of familial and ~10% of sporadic schwannomatosis, for most other cases, further causative genes remain to be discovered. Herein, we characterize the genome of a schwannomatosis family without constitutional inactivation of the SMARCB1 gene to explore novel genomic alterations predisposing individuals to the familial disease. METHODS: We performed whole-genome/exome sequencing on genomic DNA of both schwannomatosis-affected and normal members of the family. RESULTS: We identified a novel missense mutation (p.Asp208His; c.622G>C) in the coenzyme Q10 (CoQ10) biosynthesis monooxygenase 6 gene (COQ6) in schwannomatosis-affected members. The deleterious effects of the COQ6 mutations were validated by their lack of complementation in a coq6-deficient yeast mutant. Our study further indicated that the resultant haploinsufficiency of COQ6 might lead to CoQ10 deficiency and chronic overproduction of reactive oxygen species in Schwann cells. CONCLUSION: Although the exact oncogenetic mechanisms in this schwannomatosis family remain to be elucidated, our data strongly indicate a probable role of COQ6 mutation and CoQ10 deficiency in the development of familial schwannomatosis.Genet Med 16 10, 787-792.
原文英語
頁(從 - 到)787-792
頁數6
期刊Genetics in Medicine
16
發行號10
DOIs
出版狀態已發佈 - 十月 1 2014

指紋

Germ-Line Mutation
Missense Mutation
coenzyme Q10
Genome
Exome
Viverridae
Haploinsufficiency
Mutation
Neurofibromatoses
Schwann Cells
Neurilemmoma
Gene Silencing
Mixed Function Oxygenases
Schwannomatosis
Tumor Suppressor Genes
Genes
Reactive Oxygen Species
Yeasts
DNA

ASJC Scopus subject areas

  • Medicine(all)

引用此文

A germline missense mutation in COQ6 is associated with susceptibility to familial schwannomatosis. / Zhang, Keqiang; Lin, Jia Wei; Wang, Jinhui; Wu, Xiwei; Gao, Hanlin; Hsieh, Yi Chen; Hwu, Peter; Liu, Yun Ru; Su, Leila; Chiou, Hung Yi; Wang, Daidong; Yuan, Yate Ching; Whang-Peng, Jacqueline; Chiu, Wen Ta; Yen, Yun.

於: Genetics in Medicine, 卷 16, 編號 10, 01.10.2014, p. 787-792.

研究成果: 雜誌貢獻文章

Zhang, Keqiang ; Lin, Jia Wei ; Wang, Jinhui ; Wu, Xiwei ; Gao, Hanlin ; Hsieh, Yi Chen ; Hwu, Peter ; Liu, Yun Ru ; Su, Leila ; Chiou, Hung Yi ; Wang, Daidong ; Yuan, Yate Ching ; Whang-Peng, Jacqueline ; Chiu, Wen Ta ; Yen, Yun. / A germline missense mutation in COQ6 is associated with susceptibility to familial schwannomatosis. 於: Genetics in Medicine. 2014 ; 卷 16, 編號 10. 頁 787-792.
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abstract = "PURPOSE: Schwannomatosis, a subtype of neurofibromatosis, is characterized by multiple benign, nonvestibular, nonintradermal schwannomas. Although the tumor suppressor SMARCB1 gene has been frequently identified as the underlying genetic cause of half of familial and ~10{\%} of sporadic schwannomatosis, for most other cases, further causative genes remain to be discovered. Herein, we characterize the genome of a schwannomatosis family without constitutional inactivation of the SMARCB1 gene to explore novel genomic alterations predisposing individuals to the familial disease.METHODS: We performed whole-genome/exome sequencing on genomic DNA of both schwannomatosis-affected and normal members of the family.RESULTS: We identified a novel missense mutation (p.Asp208His; c.622G>C) in the coenzyme Q10 (CoQ10) biosynthesis monooxygenase 6 gene (COQ6) in schwannomatosis-affected members. The deleterious effects of the COQ6 mutations were validated by their lack of complementation in a coq6-deficient yeast mutant. Our study further indicated that the resultant haploinsufficiency of COQ6 might lead to CoQ10 deficiency and chronic overproduction of reactive oxygen species in Schwann cells.CONCLUSION: Although the exact oncogenetic mechanisms in this schwannomatosis family remain to be elucidated, our data strongly indicate a probable role of COQ6 mutation and CoQ10 deficiency in the development of familial schwannomatosis.Genet Med 16 10, 787-792.",
author = "Keqiang Zhang and Lin, {Jia Wei} and Jinhui Wang and Xiwei Wu and Hanlin Gao and Hsieh, {Yi Chen} and Peter Hwu and Liu, {Yun Ru} and Leila Su and Chiou, {Hung Yi} and Daidong Wang and Yuan, {Yate Ching} and Jacqueline Whang-Peng and Chiu, {Wen Ta} and Yun Yen",
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TY - JOUR

T1 - A germline missense mutation in COQ6 is associated with susceptibility to familial schwannomatosis

AU - Zhang, Keqiang

AU - Lin, Jia Wei

AU - Wang, Jinhui

AU - Wu, Xiwei

AU - Gao, Hanlin

AU - Hsieh, Yi Chen

AU - Hwu, Peter

AU - Liu, Yun Ru

AU - Su, Leila

AU - Chiou, Hung Yi

AU - Wang, Daidong

AU - Yuan, Yate Ching

AU - Whang-Peng, Jacqueline

AU - Chiu, Wen Ta

AU - Yen, Yun

PY - 2014/10/1

Y1 - 2014/10/1

N2 - PURPOSE: Schwannomatosis, a subtype of neurofibromatosis, is characterized by multiple benign, nonvestibular, nonintradermal schwannomas. Although the tumor suppressor SMARCB1 gene has been frequently identified as the underlying genetic cause of half of familial and ~10% of sporadic schwannomatosis, for most other cases, further causative genes remain to be discovered. Herein, we characterize the genome of a schwannomatosis family without constitutional inactivation of the SMARCB1 gene to explore novel genomic alterations predisposing individuals to the familial disease.METHODS: We performed whole-genome/exome sequencing on genomic DNA of both schwannomatosis-affected and normal members of the family.RESULTS: We identified a novel missense mutation (p.Asp208His; c.622G>C) in the coenzyme Q10 (CoQ10) biosynthesis monooxygenase 6 gene (COQ6) in schwannomatosis-affected members. The deleterious effects of the COQ6 mutations were validated by their lack of complementation in a coq6-deficient yeast mutant. Our study further indicated that the resultant haploinsufficiency of COQ6 might lead to CoQ10 deficiency and chronic overproduction of reactive oxygen species in Schwann cells.CONCLUSION: Although the exact oncogenetic mechanisms in this schwannomatosis family remain to be elucidated, our data strongly indicate a probable role of COQ6 mutation and CoQ10 deficiency in the development of familial schwannomatosis.Genet Med 16 10, 787-792.

AB - PURPOSE: Schwannomatosis, a subtype of neurofibromatosis, is characterized by multiple benign, nonvestibular, nonintradermal schwannomas. Although the tumor suppressor SMARCB1 gene has been frequently identified as the underlying genetic cause of half of familial and ~10% of sporadic schwannomatosis, for most other cases, further causative genes remain to be discovered. Herein, we characterize the genome of a schwannomatosis family without constitutional inactivation of the SMARCB1 gene to explore novel genomic alterations predisposing individuals to the familial disease.METHODS: We performed whole-genome/exome sequencing on genomic DNA of both schwannomatosis-affected and normal members of the family.RESULTS: We identified a novel missense mutation (p.Asp208His; c.622G>C) in the coenzyme Q10 (CoQ10) biosynthesis monooxygenase 6 gene (COQ6) in schwannomatosis-affected members. The deleterious effects of the COQ6 mutations were validated by their lack of complementation in a coq6-deficient yeast mutant. Our study further indicated that the resultant haploinsufficiency of COQ6 might lead to CoQ10 deficiency and chronic overproduction of reactive oxygen species in Schwann cells.CONCLUSION: Although the exact oncogenetic mechanisms in this schwannomatosis family remain to be elucidated, our data strongly indicate a probable role of COQ6 mutation and CoQ10 deficiency in the development of familial schwannomatosis.Genet Med 16 10, 787-792.

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U2 - 10.1038/gim.2014.39

DO - 10.1038/gim.2014.39

M3 - Article

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EP - 792

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 10

ER -