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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...
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/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. |
format | Online Article Text |
id | pubmed-8963843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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
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title_full | Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
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title_fullStr | Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
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title_full_unstemmed | Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
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title_short | Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1
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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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