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Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1

Meckel syndrome (MKS), also known as the Meckel–Gruber syndrome, is a severe pleiotropic autosomal recessive developmental disorder caused by dysfunction of the primary cilia during early embryogenesis. The diagnostic criteria are based on clinical variability and genetic heterogeneity. Mutations in...

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Autores principales: Lin, Tingting, Ma, Yongyi, Zhou, Danni, Sun, Liwei, Chen, Ke, Xiang, Yezhou, Tong, Keya, Jia, Chaoli, Jiang, Kean, Liu, Dongyun, Huang, Guoning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963843/
https://www.ncbi.nlm.nih.gov/pubmed/35360848
http://dx.doi.org/10.3389/fgene.2022.843931
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author Lin, Tingting
Ma, Yongyi
Zhou, Danni
Sun, Liwei
Chen, Ke
Xiang, Yezhou
Tong, Keya
Jia, Chaoli
Jiang, Kean
Liu, Dongyun
Huang, Guoning
author_facet Lin, Tingting
Ma, Yongyi
Zhou, Danni
Sun, Liwei
Chen, Ke
Xiang, Yezhou
Tong, Keya
Jia, Chaoli
Jiang, Kean
Liu, Dongyun
Huang, Guoning
author_sort Lin, Tingting
collection PubMed
description Meckel syndrome (MKS), also known as the Meckel–Gruber syndrome, is a severe pleiotropic autosomal recessive developmental disorder caused by dysfunction of the primary cilia during early embryogenesis. The diagnostic criteria are based on clinical variability and genetic heterogeneity. Mutations in the MKS1 gene constitute approximately 7% of all MKS cases. Herein, we present a non-consanguineous couple with three abnormal pregnancies as the fetuses showed MKS-related phenotypes of the central nervous system malformation and postaxial polydactyly. Whole-exome sequencing identified two novel heterozygous mutations of MKS1: c.350C>A and c.1408-14A>G. The nonsense mutation c.350C>A produced a premature stop codon and induced the truncation of the MKS1 protein (p.S117*). Reverse-transcription polymerase chain reaction (RT-PCR) showed that c.1408-14A>G skipped exon 16 and encoded the mutant MKS1 p.E471Lfs*92. Functional studies showed that these two mutations disrupted the B9–C2 domain of the MKS1 protein and attenuated the interactions with B9D2, the essential component of the ciliary transition zone. The couple finally got a healthy baby through preimplantation genetic testing for monogenic disorder (PGT-M) with haplotype linkage analysis. Thus, this study expanded the mutation spectrum of MKS1 and elucidated the genetic heterogeneity of MKS1 in clinical cases.
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spelling pubmed-89638432022-03-30 Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1 Lin, Tingting Ma, Yongyi Zhou, Danni Sun, Liwei Chen, Ke Xiang, Yezhou Tong, Keya Jia, Chaoli Jiang, Kean Liu, Dongyun Huang, Guoning Front Genet Genetics Meckel syndrome (MKS), also known as the Meckel–Gruber syndrome, is a severe pleiotropic autosomal recessive developmental disorder caused by dysfunction of the primary cilia during early embryogenesis. The diagnostic criteria are based on clinical variability and genetic heterogeneity. Mutations in the MKS1 gene constitute approximately 7% of all MKS cases. Herein, we present a non-consanguineous couple with three abnormal pregnancies as the fetuses showed MKS-related phenotypes of the central nervous system malformation and postaxial polydactyly. Whole-exome sequencing identified two novel heterozygous mutations of MKS1: c.350C>A and c.1408-14A>G. The nonsense mutation c.350C>A produced a premature stop codon and induced the truncation of the MKS1 protein (p.S117*). Reverse-transcription polymerase chain reaction (RT-PCR) showed that c.1408-14A>G skipped exon 16 and encoded the mutant MKS1 p.E471Lfs*92. Functional studies showed that these two mutations disrupted the B9–C2 domain of the MKS1 protein and attenuated the interactions with B9D2, the essential component of the ciliary transition zone. The couple finally got a healthy baby through preimplantation genetic testing for monogenic disorder (PGT-M) with haplotype linkage analysis. Thus, this study expanded the mutation spectrum of MKS1 and elucidated the genetic heterogeneity of MKS1 in clinical cases. Frontiers Media S.A. 2022-03-14 /pmc/articles/PMC8963843/ /pubmed/35360848 http://dx.doi.org/10.3389/fgene.2022.843931 Text en Copyright © 2022 Lin, Ma, Zhou, Sun, Chen, Xiang, Tong, Jia, Jiang, Liu and Huang. 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 Genetics
Lin, Tingting
Ma, Yongyi
Zhou, Danni
Sun, Liwei
Chen, Ke
Xiang, Yezhou
Tong, Keya
Jia, Chaoli
Jiang, Kean
Liu, Dongyun
Huang, Guoning
Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
title Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
title_full Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
title_fullStr Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
title_full_unstemmed Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
title_short Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
title_sort case report: preimplantation genetic testing for meckel syndrome induced by novel compound heterozygous mutations of mks1
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963843/
https://www.ncbi.nlm.nih.gov/pubmed/35360848
http://dx.doi.org/10.3389/fgene.2022.843931
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