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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9708884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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