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A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice

We used whole exome sequence analysis to investigate a possible genetic etiology for a patient with the phenotype of intrauterine growth restriction, microcephaly, developmental delay, failure to thrive, congenital bilateral hip dysplasia, cerebral and cerebellar atrophy, hydrocephalus, and congenit...

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Autores principales: Tuzovic, Lea, Yu, Lan, Zeng, Wenqi, Li, Xiang, Lu, Hong, Lu, Hsiao-Mei, Gonzalez, Kelly DF, Chung, Wendy K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927488/
https://www.ncbi.nlm.nih.gov/pubmed/25003005
http://dx.doi.org/10.4161/rdis.26144
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author Tuzovic, Lea
Yu, Lan
Zeng, Wenqi
Li, Xiang
Lu, Hong
Lu, Hsiao-Mei
Gonzalez, Kelly DF
Chung, Wendy K
author_facet Tuzovic, Lea
Yu, Lan
Zeng, Wenqi
Li, Xiang
Lu, Hong
Lu, Hsiao-Mei
Gonzalez, Kelly DF
Chung, Wendy K
author_sort Tuzovic, Lea
collection PubMed
description We used whole exome sequence analysis to investigate a possible genetic etiology for a patient with the phenotype of intrauterine growth restriction, microcephaly, developmental delay, failure to thrive, congenital bilateral hip dysplasia, cerebral and cerebellar atrophy, hydrocephalus, and congenital diaphragmatic hernia (CDH). Whole exome sequencing identified a novel de novo c.2722G > T (p.E908X) mutation in the Myosin Heavy Chain 10 gene (MYH10) which encodes for non-muscle heavy chain II B (NMHC IIB). Mutations in MYH10 have not been previously described in association with human disease. The E908X mutation is located in the coiled-coil region of the protein and is expected to delete the tail domain and disrupt filament assembly. Nonmuscle myosin IIs (NM IIs) are a group of ubiquitously expressed proteins, and NM II B is specifically enriched in neuronal tissue and is thought to be important in neuronal migration. It is also expressed in cardiac myocytes along with NM IIC. Homozygous NMHC II B-/B- mouse knockouts die by embryonic day (E)14.5 with severe cardiac defects (membranous ventricular septal defect and cardiac outflow tract abnormalities) and neurodevelopmental disorders (progressive hydrocephalus and neuronal migrational abnormalities). A heterozygous MYH10 loss of function mutation produces a severe neurologic phenotype and CDH but no apparent cardiac phenotype and suggests that MYH10 may represent a novel gene for brain malformations and/or CDH.
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spelling pubmed-39274882014-07-07 A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice Tuzovic, Lea Yu, Lan Zeng, Wenqi Li, Xiang Lu, Hong Lu, Hsiao-Mei Gonzalez, Kelly DF Chung, Wendy K Rare Dis Research Paper We used whole exome sequence analysis to investigate a possible genetic etiology for a patient with the phenotype of intrauterine growth restriction, microcephaly, developmental delay, failure to thrive, congenital bilateral hip dysplasia, cerebral and cerebellar atrophy, hydrocephalus, and congenital diaphragmatic hernia (CDH). Whole exome sequencing identified a novel de novo c.2722G > T (p.E908X) mutation in the Myosin Heavy Chain 10 gene (MYH10) which encodes for non-muscle heavy chain II B (NMHC IIB). Mutations in MYH10 have not been previously described in association with human disease. The E908X mutation is located in the coiled-coil region of the protein and is expected to delete the tail domain and disrupt filament assembly. Nonmuscle myosin IIs (NM IIs) are a group of ubiquitously expressed proteins, and NM II B is specifically enriched in neuronal tissue and is thought to be important in neuronal migration. It is also expressed in cardiac myocytes along with NM IIC. Homozygous NMHC II B-/B- mouse knockouts die by embryonic day (E)14.5 with severe cardiac defects (membranous ventricular septal defect and cardiac outflow tract abnormalities) and neurodevelopmental disorders (progressive hydrocephalus and neuronal migrational abnormalities). A heterozygous MYH10 loss of function mutation produces a severe neurologic phenotype and CDH but no apparent cardiac phenotype and suggests that MYH10 may represent a novel gene for brain malformations and/or CDH. Landes Bioscience 2013-08-14 /pmc/articles/PMC3927488/ /pubmed/25003005 http://dx.doi.org/10.4161/rdis.26144 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Research Paper
Tuzovic, Lea
Yu, Lan
Zeng, Wenqi
Li, Xiang
Lu, Hong
Lu, Hsiao-Mei
Gonzalez, Kelly DF
Chung, Wendy K
A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice
title A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice
title_full A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice
title_fullStr A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice
title_full_unstemmed A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice
title_short A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice
title_sort human de novo mutation in myh10 phenocopies the loss of function mutation in mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927488/
https://www.ncbi.nlm.nih.gov/pubmed/25003005
http://dx.doi.org/10.4161/rdis.26144
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