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Expansion of the mutation spectrum and phenotype of USP7-related neurodevelopmental disorder

BACKGROUND: Hao-fountain syndrome (HAFOUS) is a neurodevelopmental syndrome characterized by global developmental and severe language delays, behavioral abnormalities (including autism), and mild dysmorphic impairment of intellectual development. It is a dominant genetic disease caused by USP7 gene...

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Autores principales: Zheng, Hong, Mei, Shiyue, Li, Fuwei, Wei, Liwan, Wang, Yanchu, Huang, Jinrong, Zhang, Feng, Huang, Jia, Liu, Yanping, Gu, Weiyue, Liu, Hongyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708884/
https://www.ncbi.nlm.nih.gov/pubmed/36466803
http://dx.doi.org/10.3389/fnmol.2022.970649
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author Zheng, Hong
Mei, Shiyue
Li, Fuwei
Wei, Liwan
Wang, Yanchu
Huang, Jinrong
Zhang, Feng
Huang, Jia
Liu, Yanping
Gu, Weiyue
Liu, Hongyan
author_facet Zheng, Hong
Mei, Shiyue
Li, Fuwei
Wei, Liwan
Wang, Yanchu
Huang, Jinrong
Zhang, Feng
Huang, Jia
Liu, Yanping
Gu, Weiyue
Liu, Hongyan
author_sort Zheng, Hong
collection PubMed
description BACKGROUND: Hao-fountain syndrome (HAFOUS) is a neurodevelopmental syndrome characterized by global developmental and severe language delays, behavioral abnormalities (including autism), and mild dysmorphic impairment of intellectual development. It is a dominant genetic disease caused by USP7 gene (*602519) mutations on chromosome 16p13.2. So far, only 15 cases with 14 deleterious variants in the USP7 gene have been reported. MATERIALS AND METHODS: This study describes three unrelated patients with USP7 variants. Besides, we identified novel de novo heterozygous USP7 variants using trio-whole exome sequencing and verified by Sanger sequencing. Furthermore, clinical characteristics were evaluated by reviewing the medical records. RESULTS: The three identified variants, i.e., one frameshift variant (c.247_250del, p.Glu83Argfs × 18) and two missense variants (c.992A > G, p.Tyr331Cys; c.835T > G, p.Leu279Val) are unreported. The predominant clinical manifestations of the three patients included: DD/ID; language impairment; abnormal behavior; abnormal brain magnetic resonance (dilation of lateral ventricles, dilation of Virchow-Robin spaces, dilated the third ventricle, abnormal cerebral white matter morphology in bilateral occipital lobes, hypodysplasia of the corpus callosum, arachnoid cyst, delayed myelination, and widened subarachnoid space); some also had facial abnormalities. CONCLUSION: In summary, DD/ID is the most prevalent clinical phenotype of HAFOUS, although some patients also exhibit language and behavioral abnormalities. For the first time in China, we identified three variants of the USP7 gene using whole-genome sequence data. This work expands the USP7 gene mutation spectrum and provides additional clinical data on the clinical phenotype of HAFOUS.
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spelling pubmed-97088842022-12-01 Expansion of the mutation spectrum and phenotype of USP7-related neurodevelopmental disorder Zheng, Hong Mei, Shiyue Li, Fuwei Wei, Liwan Wang, Yanchu Huang, Jinrong Zhang, Feng Huang, Jia Liu, Yanping Gu, Weiyue Liu, Hongyan Front Mol Neurosci Molecular Neuroscience BACKGROUND: Hao-fountain syndrome (HAFOUS) is a neurodevelopmental syndrome characterized by global developmental and severe language delays, behavioral abnormalities (including autism), and mild dysmorphic impairment of intellectual development. It is a dominant genetic disease caused by USP7 gene (*602519) mutations on chromosome 16p13.2. So far, only 15 cases with 14 deleterious variants in the USP7 gene have been reported. MATERIALS AND METHODS: This study describes three unrelated patients with USP7 variants. Besides, we identified novel de novo heterozygous USP7 variants using trio-whole exome sequencing and verified by Sanger sequencing. Furthermore, clinical characteristics were evaluated by reviewing the medical records. RESULTS: The three identified variants, i.e., one frameshift variant (c.247_250del, p.Glu83Argfs × 18) and two missense variants (c.992A > G, p.Tyr331Cys; c.835T > G, p.Leu279Val) are unreported. The predominant clinical manifestations of the three patients included: DD/ID; language impairment; abnormal behavior; abnormal brain magnetic resonance (dilation of lateral ventricles, dilation of Virchow-Robin spaces, dilated the third ventricle, abnormal cerebral white matter morphology in bilateral occipital lobes, hypodysplasia of the corpus callosum, arachnoid cyst, delayed myelination, and widened subarachnoid space); some also had facial abnormalities. CONCLUSION: In summary, DD/ID is the most prevalent clinical phenotype of HAFOUS, although some patients also exhibit language and behavioral abnormalities. For the first time in China, we identified three variants of the USP7 gene using whole-genome sequence data. This work expands the USP7 gene mutation spectrum and provides additional clinical data on the clinical phenotype of HAFOUS. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9708884/ /pubmed/36466803 http://dx.doi.org/10.3389/fnmol.2022.970649 Text en Copyright © 2022 Zheng, Mei, Li, Wei, Wang, Huang, Zhang, Huang, Liu, Gu and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Zheng, Hong
Mei, Shiyue
Li, Fuwei
Wei, Liwan
Wang, Yanchu
Huang, Jinrong
Zhang, Feng
Huang, Jia
Liu, Yanping
Gu, Weiyue
Liu, Hongyan
Expansion of the mutation spectrum and phenotype of USP7-related neurodevelopmental disorder
title Expansion of the mutation spectrum and phenotype of USP7-related neurodevelopmental disorder
title_full Expansion of the mutation spectrum and phenotype of USP7-related neurodevelopmental disorder
title_fullStr Expansion of the mutation spectrum and phenotype of USP7-related neurodevelopmental disorder
title_full_unstemmed Expansion of the mutation spectrum and phenotype of USP7-related neurodevelopmental disorder
title_short Expansion of the mutation spectrum and phenotype of USP7-related neurodevelopmental disorder
title_sort expansion of the mutation spectrum and phenotype of usp7-related neurodevelopmental disorder
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708884/
https://www.ncbi.nlm.nih.gov/pubmed/36466803
http://dx.doi.org/10.3389/fnmol.2022.970649
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