A novel SYNE2 mutation identified by whole exome sequencing in a Korean family with Emery-Dreifuss muscular dystrophy

Abstract Background Limb-girdle muscular dystrophies (LGMDs) are large group of heterogeneous genetic diseases, having a hallmark feature of muscle weakness. Pathogenic mutations in the gene encoding the giant skeletal muscle protein titin (TTN) are associated with several muscle disorders, including cardiomyopathy, recessive congenital myopathies and limb-girdle muscular dystrophy (LGMD) type10. The phenotypic spectrum of titinopathies is expanding, as next generation sequencing (NGS) technology makes screening of this large gene possible. Aim This study aimed to identify the pathogenic variant in a consanguineous Pakistani family with autosomal recessive LGMD type 10. Methods DNA from peripheral blood samples were obtained, whole exome sequencing (WES) was performed and several molecular and bioinformatics analysis were conducted to identify the pathogenic variant. TTN coding and near coding regions were further amplified using PCR and sequenced via Sanger sequencing. Results Whole exome sequencing analysis revealed a novel homozygous missense variant (c.98807G > A; p.Arg32936His) in the TTN gene in the index patients. No heterozygous individuals in the family presented LGMD features. The variant p.Arg32936His leads to a substitution of the arginine amino acid at position 32,936 into histidine possibly causing LGMD type 10. Conclusion We identified a homozygous missense variant in TTN, which likely explains LGMD type 10 in this family in line with similar previously reported data. Our study concludes that WES is a successful molecular diagnostic tool to identify pathogenic variants in large genes such as TTN in highly inbred population.

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Whole-Exome Sequencing Identifies Small Mutations in Pakistani Muscular Dystrophy Patients

Genetic Testing and Molecular Biomarkers ◽

10.1089/gtmb.2020.0246 ◽

2021 ◽

Vol 25 (3) ◽

pp. 218-226

Author(s):

Mehwish Zehravi ◽

Mohsin Wahid ◽

Junaid Ashraf ◽

Tehseen Fatima

Keyword(s):

Muscular Dystrophy ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Whole Exome

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Whole-exome sequencing in Tricho-rhino-phalangeal syndrome (TRPS) type I in a Korean family

Genes & Genomics ◽

10.1007/s13258-016-0508-1 ◽

2016 ◽

Vol 39 (4) ◽

pp. 417-422 ◽

Cited By ~ 1

Author(s):

Byulee Yoon ◽

Yun-Ji Kim ◽

Seung-Yeol Son ◽

Kyudong Han ◽

Byung Cheol Park

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Type I ◽

Korean Family ◽

Whole Exome

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Identification of a novel splicing mutation within SLC17A8 in a Korean family with hearing loss by whole-exome sequencing

Gene ◽

10.1016/j.gene.2017.06.040 ◽

2017 ◽

Vol 627 ◽

pp. 233-238 ◽

Cited By ~ 4

Author(s):

Nari Ryu ◽

Seokwon Lee ◽

Hong-Joon Park ◽

Byeonghyeon Lee ◽

Tae-Jun Kwon ◽

...

Keyword(s):

Hearing Loss ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Splicing Mutation ◽

Korean Family ◽

Whole Exome

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Whole Exome Sequencing Aids The Diagnosis of Fetal Skeletal Dysplasia

10.21203/rs.3.rs-46976/v1 ◽

2020 ◽

Author(s):

Hui Tang ◽

Qin Zhang ◽

Linliang Yin ◽

Jingjing Xiang ◽

Jing Wang ◽

...

Keyword(s):

Muscular Dystrophy ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Skeletal Dysplasia ◽

Clinical Symptoms ◽

Single Nucleotide Polymorphism Array ◽

Snp Array ◽

Somatic Mosaicism ◽

Single Nucleotide ◽

Whole Exome

Abstract Background: Skeletal dysplasia is a complex group of bone and cartilage disorders with strong clinical and genetical heterogeneousity. Several types have prenatal phenotypes. And it is difficult to make a molecular diagnosis rapidly due to lacking family history and non-specific and limited clinical symptoms in utero. This study aims to diagnose 16 Chinese fetuses with skeletal dysplasia.Methods: Single nucleotide polymorphism-array (SNP-array) was performed in 12 of 16 samples. If no microdeletions or microreplications related to skeletal dysplasia were detected, whole-exome sequencing (WES) was adopted. And the last four cases only got whole-exome sequencing for analyzing copy number variants and single nucleotide variations at the same time.Results: Among the 16 cases, 12 patients received definitive diagnosis and we detected one deletion in DMD gene by SNP-array and 15 variants of 6 genes including FGFR3, COL1A1, COL1A2, ALPL, HSPG2 and DYNC2H1. 8 variants of COL1A1, COL1A2, ALPL and HSPG2 are novel. And somatic mosaicism in asymptomatic parent with mutations in COL1A1 or COL1A2 was observed.Conclusions: In general, our study expanded the prenatal phenotypes in Duchenne muscular dystrophy (DMD)/ Becker muscular dystrophy (BMD), found 8 novel variants and elucidated that the utilization of whole-exome sequencing improved the diagnosis yield of skeletal dysplasia and provided useful genetic counseling guidance for parents.

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Case Report: Whole-Exome Sequencing With MLPA Revealed Variants in Two Genes in a Patient With Combined Manifestations of Spinal Muscular Atrophy and Duchenne Muscular Dystrophy

Frontiers in Genetics ◽

10.3389/fgene.2021.605611 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yu Xia ◽

Yijie Feng ◽

Lu Xu ◽

Xiaoyang Chen ◽

Feng Gao ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Spinal Muscular Atrophy ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Muscular Atrophy ◽

Genetic Disorder ◽

Clinical Manifestations ◽

Chinese Family ◽

Whole Exome

Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are two common kinds of neuromuscular disorders sharing various similarities in clinical manifestations. SMA is an autosomal recessive genetic disorder that results from biallelic mutations of the survival motor neuron 1 gene (SMN1; OMIM 600354) on the 5q13 chromosome. DMD is an X-linked disorder caused by defects in the DMD gene (OMIM 300377) on the X chromosome. Here, for the first time, we report a case from a Chinese family who present with clinical manifestations of both two diseases, including poor motor development and progressive muscle weakness. We identified a homozygous deletion in exons 7 and 8 of the SMN1 gene and a deletion in exon 50 of the DMD gene by whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA). This case expands our understanding of diagnosis for synchronous SMA and DMD and highlights the importance of various genetic testing methods, including WES, in differential diagnosis of neuromuscular diseases.

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