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Clinical observation and genetic analysis of a SYNS1 family caused by novel NOG gene mutation
OBJECTIVE: Analyze the clinical and genetic characteristics of a rare Chinese family with Multiple synostoses syndrome and identify the causative variant with the high‐throughput sequencing approach. METHODS: The medical history investigation, physical examination, imaging examination, and audiologi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034678/ https://www.ncbi.nlm.nih.gov/pubmed/35332702 http://dx.doi.org/10.1002/mgg3.1933 |
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author | Zhang, Zhao Lu, Yu Cao, Jing‐Yuan Wang, Li Li, Lin‐Ke Wang, Chao Ye, Xuan Ji, Yi‐Ming Tu, Lin‐Yi Sun, Yi |
author_facet | Zhang, Zhao Lu, Yu Cao, Jing‐Yuan Wang, Li Li, Lin‐Ke Wang, Chao Ye, Xuan Ji, Yi‐Ming Tu, Lin‐Yi Sun, Yi |
author_sort | Zhang, Zhao |
collection | PubMed |
description | OBJECTIVE: Analyze the clinical and genetic characteristics of a rare Chinese family with Multiple synostoses syndrome and identify the causative variant with the high‐throughput sequencing approach. METHODS: The medical history investigation, physical examination, imaging examination, and audiological examination of the family members were performed. DNA samples were extracted from the family members. The candidate variant was identified by performing whole‐exome sequencing of the proband, then verified by Sanger sequencing in the family. RESULTS: The family named HBSY‐018 from Hubei province had 18 subjects in three generations, and six subjects were diagnosed with conductive or mixed hearing loss. Meanwhile, characteristic features including short philtrum, hemicylindrical nose, and hypoplastic alae nasi were noticed among those patients. Symptoms of proximal interdigital joint adhesion and inflexibility were found. The family was diagnosed as Multiple synostoses syndrome type 1 (SYNS1).The inheritance pattern of this family was autosomal dominant. A novel mutation in the NOG gene c.533G>A was identified by performing whole‐exome sequencing of the proband. The substitution of cysteine encoding 178th position with tyrosine (p.Cys178Tyr) was caused by this mutation, which was conserved across species. Co‐segregation of disease phenotypes was demonstrated by the family verification. CONCLUSION: The family diagnosed as SYNS1 was caused by the novel mutation (c.533G>A) of NOG. The combination of clinical diagnosis and molecular diagnosis had improved the understanding of this rare disease and provided a scientific basis for genetic counseling in the family. |
format | Online Article Text |
id | pubmed-9034678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90346782022-04-25 Clinical observation and genetic analysis of a SYNS1 family caused by novel NOG gene mutation Zhang, Zhao Lu, Yu Cao, Jing‐Yuan Wang, Li Li, Lin‐Ke Wang, Chao Ye, Xuan Ji, Yi‐Ming Tu, Lin‐Yi Sun, Yi Mol Genet Genomic Med Original Articles OBJECTIVE: Analyze the clinical and genetic characteristics of a rare Chinese family with Multiple synostoses syndrome and identify the causative variant with the high‐throughput sequencing approach. METHODS: The medical history investigation, physical examination, imaging examination, and audiological examination of the family members were performed. DNA samples were extracted from the family members. The candidate variant was identified by performing whole‐exome sequencing of the proband, then verified by Sanger sequencing in the family. RESULTS: The family named HBSY‐018 from Hubei province had 18 subjects in three generations, and six subjects were diagnosed with conductive or mixed hearing loss. Meanwhile, characteristic features including short philtrum, hemicylindrical nose, and hypoplastic alae nasi were noticed among those patients. Symptoms of proximal interdigital joint adhesion and inflexibility were found. The family was diagnosed as Multiple synostoses syndrome type 1 (SYNS1).The inheritance pattern of this family was autosomal dominant. A novel mutation in the NOG gene c.533G>A was identified by performing whole‐exome sequencing of the proband. The substitution of cysteine encoding 178th position with tyrosine (p.Cys178Tyr) was caused by this mutation, which was conserved across species. Co‐segregation of disease phenotypes was demonstrated by the family verification. CONCLUSION: The family diagnosed as SYNS1 was caused by the novel mutation (c.533G>A) of NOG. The combination of clinical diagnosis and molecular diagnosis had improved the understanding of this rare disease and provided a scientific basis for genetic counseling in the family. John Wiley and Sons Inc. 2022-03-25 /pmc/articles/PMC9034678/ /pubmed/35332702 http://dx.doi.org/10.1002/mgg3.1933 Text en © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Zhang, Zhao Lu, Yu Cao, Jing‐Yuan Wang, Li Li, Lin‐Ke Wang, Chao Ye, Xuan Ji, Yi‐Ming Tu, Lin‐Yi Sun, Yi Clinical observation and genetic analysis of a SYNS1 family caused by novel NOG gene mutation |
title | Clinical observation and genetic analysis of a SYNS1 family caused by novel NOG gene mutation |
title_full | Clinical observation and genetic analysis of a SYNS1 family caused by novel NOG gene mutation |
title_fullStr | Clinical observation and genetic analysis of a SYNS1 family caused by novel NOG gene mutation |
title_full_unstemmed | Clinical observation and genetic analysis of a SYNS1 family caused by novel NOG gene mutation |
title_short | Clinical observation and genetic analysis of a SYNS1 family caused by novel NOG gene mutation |
title_sort | clinical observation and genetic analysis of a syns1 family caused by novel nog gene mutation |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034678/ https://www.ncbi.nlm.nih.gov/pubmed/35332702 http://dx.doi.org/10.1002/mgg3.1933 |
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