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Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review

INTRODUCTION: Cockayne syndrome (CS) is a rare multisystemic autosomal recessive disease. The primary manifestations of which are developmental delay, neurological impairment, abnormal skin sensitivity to sunlight and unique facial appearance as sunken eyes, large ears, and thin large nose. The diso...

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Autores principales: Kou, Yao, Shboul, Mohammad, Wang, Zhihao, Shersheer, Qasem, Lyu, Zhaojie, Liu, Peirong, Zhao, Xiaodong, Tian, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112894/
https://www.ncbi.nlm.nih.gov/pubmed/30113454
http://dx.doi.org/10.1097/MD.0000000000011636
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author Kou, Yao
Shboul, Mohammad
Wang, Zhihao
Shersheer, Qasem
Lyu, Zhaojie
Liu, Peirong
Zhao, Xiaodong
Tian, Jing
author_facet Kou, Yao
Shboul, Mohammad
Wang, Zhihao
Shersheer, Qasem
Lyu, Zhaojie
Liu, Peirong
Zhao, Xiaodong
Tian, Jing
author_sort Kou, Yao
collection PubMed
description INTRODUCTION: Cockayne syndrome (CS) is a rare multisystemic autosomal recessive disease. The primary manifestations of which are developmental delay, neurological impairment, abnormal skin sensitivity to sunlight and unique facial appearance as sunken eyes, large ears, and thin large nose. The disorders of the nucleotide excision repair system significantly are caused by mutations of Excision repair cross-complementing group 6 (ERCC6) and Excision repair cross-complementing group 8 (ERCC8) genes, and the ERCC6 gene mutations are present in approximately 65% of cases. CASE PRESENTATION: Here we described a girl in a consanguineous Jordanian family with abnormal facial appearance and postnatal growth delay. She was not able to gain weight. Her condition deteriorated progressively and she developed difficulty of swallowing even to water. The patient was diagnosed as CS based on her facial appearance and neurologic dysfunction. The patient was examined at 3 years old, and died at 4 years old. CONCLUSION: Genetic analysis and sequencing revealed homozygosity for a novel frame shift mutation c.2911_2915del5ins9 (p.Lys971TryfsX14) in the ERCC6. The mutation is predicted to delete 5 nucleotides and add 9 nucleotides with a premature termination, resulting in approximately 34% length reduction of the wild-type transcript. The multisystem malformations of CS are clinically heterogeneous. The frame shift mutation of ERCC6 found in this patient is a novel one, which caused postnatal growth failure and early death. Our findings indicate truncated mutation in CS lead to more severe CS phenotype and add to the genotype–phenotype correlations in CS.
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spelling pubmed-61128942018-09-07 Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review Kou, Yao Shboul, Mohammad Wang, Zhihao Shersheer, Qasem Lyu, Zhaojie Liu, Peirong Zhao, Xiaodong Tian, Jing Medicine (Baltimore) Research Article INTRODUCTION: Cockayne syndrome (CS) is a rare multisystemic autosomal recessive disease. The primary manifestations of which are developmental delay, neurological impairment, abnormal skin sensitivity to sunlight and unique facial appearance as sunken eyes, large ears, and thin large nose. The disorders of the nucleotide excision repair system significantly are caused by mutations of Excision repair cross-complementing group 6 (ERCC6) and Excision repair cross-complementing group 8 (ERCC8) genes, and the ERCC6 gene mutations are present in approximately 65% of cases. CASE PRESENTATION: Here we described a girl in a consanguineous Jordanian family with abnormal facial appearance and postnatal growth delay. She was not able to gain weight. Her condition deteriorated progressively and she developed difficulty of swallowing even to water. The patient was diagnosed as CS based on her facial appearance and neurologic dysfunction. The patient was examined at 3 years old, and died at 4 years old. CONCLUSION: Genetic analysis and sequencing revealed homozygosity for a novel frame shift mutation c.2911_2915del5ins9 (p.Lys971TryfsX14) in the ERCC6. The mutation is predicted to delete 5 nucleotides and add 9 nucleotides with a premature termination, resulting in approximately 34% length reduction of the wild-type transcript. The multisystem malformations of CS are clinically heterogeneous. The frame shift mutation of ERCC6 found in this patient is a novel one, which caused postnatal growth failure and early death. Our findings indicate truncated mutation in CS lead to more severe CS phenotype and add to the genotype–phenotype correlations in CS. Wolters Kluwer Health 2018-08-17 /pmc/articles/PMC6112894/ /pubmed/30113454 http://dx.doi.org/10.1097/MD.0000000000011636 Text en Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by/4.0 This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
spellingShingle Research Article
Kou, Yao
Shboul, Mohammad
Wang, Zhihao
Shersheer, Qasem
Lyu, Zhaojie
Liu, Peirong
Zhao, Xiaodong
Tian, Jing
Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review
title Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review
title_full Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review
title_fullStr Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review
title_full_unstemmed Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review
title_short Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review
title_sort novel frame shift mutation in ercc6 leads to a severe form of cockayne syndrome with postnatal growth failure and early death: a case report and brief literature review
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112894/
https://www.ncbi.nlm.nih.gov/pubmed/30113454
http://dx.doi.org/10.1097/MD.0000000000011636
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