scholarly journals Identification of a novel EXT2 frameshift mutation in a family with hereditary multiple exostoses by whole‐exome sequencing

2021 ◽  
Author(s):  
Mei Yang ◽  
Hanbing Xie ◽  
Bocheng Xu ◽  
Qinqin Xiang ◽  
He Wang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Frameshift Mutation ◽  
Hereditary Multiple Exostoses ◽  
Whole Exome ◽  
Multiple Exostoses

scholarly journals Identification of a Novel EXT Mutation in A Kindred With Hereditary Multiple Exostoses Using Whole-Exome Sequencing and Overview of Mutation Spectrum

2021 ◽  
Author(s):  
yanhan deng ◽  
yujian liu ◽  
wei tu ◽  
liu yang
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Mutation Spectrum ◽  
Loss Of Function ◽  
Site Mutation ◽  
Hereditary Multiple Exostoses ◽  
Multiple Osteochondromas ◽  
Online Databases ◽  
Whole Exome ◽  
Multiple Exostoses

Abstract Background: Hereditary Multiple Osteochondromas(HMO) is a rare genetic musculoskeletal disorder characterized by multiple osteochondromas that form near to the growth plates of many bones. Loss-of-function mutations in EXT1 or EXT2 that encode glycosyltrasferases are the causal mutations for most HMO patients.Methods: After collecting the family history and clinical information, we used Whole-Exome Sequencing to find the pathogenic mutations in one Chinese Hereditary Multiple Exostoses pedigree. Sanger sequencing and relevant online databases were used to validate the screened variants. Lollipop plots were drew to map the reported mutations from online databases (Multiple Osteochondroma Mutation Database and clinvar)on a linear protein domains by MutationMapper.Results: A novel heterozygous splicing-site mutation in gene EXT1 (NM_000127:exon5:c.1417+1G>C，chr8:118834703) was found in this pedigree and mutation spectrum of genes EXT1 and EXT2 were demonstrated.Conclusions: Our results help this pedigree to identify the pathogenic variant and guide the prenatal diagnosis, also expand the mutation spectrum in Hereditary Multiple Osteochondromas.

scholarly journals Identification of Novel EXT Mutations in Patients with Hereditary Multiple Exostoses Using Whole‐Exome Sequencing

2020 ◽  
Vol 12 (3) ◽  
pp. 990-996
Author(s):  
Chao Liang ◽  
Yong‐jie Wang ◽  
Yu‐xuan Wei ◽  
Yang Dong ◽  
Zhi‐chang Zhang
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Hereditary Multiple Exostoses ◽  
Whole Exome ◽  
Multiple Exostoses

Whole-exome sequencing identified a novel mutation of SLC20A2 (c.C1849T) in a Chinese family with hereditary multiple exostoses

2020 ◽  
Author(s):  
YiQiang Li ◽  
XueMei Lin ◽  
MingWei Zhu ◽  
FuXing Xun ◽  
JingChun Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Chinese Family ◽  
Bioinformatics Pipeline ◽  
Hereditary Multiple Exostoses ◽  
Whole Exome ◽  
Multiple Exostoses ◽  
Proliferation And Differentiation ◽  
Filtering Procedure

Abstract Background: Although the main causative genes for hereditary multiple exostoses (HME) are EXT-1 and EXT-2, there are still many HME patients without EXT-1 and EXT-2 mutations. This study aimed to identify novel candidate genes for the development of HME in patients without EXT-1 and EXT-2 mutations.Methods: Whole-exome sequencing was performed in a typical Chinese HME family without EXT-1 and EXT-2 mutations, followed by a combined bioinformatics pipeline including annotation and filtering process to identify candidate variants. Candidate variants were then validated by Sanger sequencing.Results: A total of 1830 original variants were revealed to be heterozygous mutations in the three patients suffering from HME that were not present in the healthy controls. Two mutations (c.C1849T in SLC20A2 and c.G506A in LETM1) were identified as a possible causative variant for HME through a bioinformatics filtering procedure and harmful prediction. Sanger sequencing results confirmed these two mutations in all patients with HME. A mutation in SLC20A2 (c.C1849T) led to a change in amino acid (p.R617C), which may be involved in the development of HME by inducing metabolic disorders of phosphate and abnormal proliferation and differentiation in chondrocytes.Conclusions: The present study revealed two mutations [SLC20A2 (c.C1849T) and LETM1 (c.G506A) in a Chinese HME family. The mutation in SLC20A2 (c.C1849T) is more likely to be involved in the development of HME.

scholarly journals Whole Exome Sequencing Identifies Three Novel Mutations in the ASPM Gene From Saudi Families Leading to Primary Microcephaly

2021 ◽  
Vol 8 ◽  
Author(s):  
Muhammad Imran Naseer ◽  
Angham Abdulrahman Abdulkareem ◽  
Osama Yousef Muthaffar ◽  
Sameera Sogaty ◽  
Hiba Alkhatabi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Frameshift Mutation ◽  
Genetic Defect ◽  
Deletion Mutation ◽  
Primary Microcephaly ◽  
Novel Mutations ◽  
Whole Exome ◽  
Novel Variants ◽  
Healthy Control

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental defect that is characterized by reduced head circumference at birth along with non-progressive intellectual disability. Till date, 25 genes related to MCPH have been reported so far in humans. The ASPM (abnormal spindle-like, microcephaly-associated) gene is among the most frequently mutated MCPH gene. We studied three different families having primary microcephaly from different regions of Saudi Arabia. Whole exome sequencing (WES) and Sanger sequencing were done to identify the genetic defect. Collectively, three novel variants were identified in the ASPM gene from three different primary microcephaly families. Family 1, showed a deletion mutation leading to a frameshift mutation c.1003del. (p.Val335*) in exon 3 of the ASPM gene and family 2, also showed deletion mutation leading to frameshift mutation c.1047del (p.Gln349Hisfs*18), while in family 3, we identified a missense mutation c.5623A>G leading to a change in protein (p.Lys1875Glu) in exon 18 of the ASPM gene underlying the disorder. The identified respective mutations were ruled out in 100 healthy control samples. In conclusion, we found three novel mutations in the ASPM gene in Saudi families that will help to establish a disease database for specified mutations in Saudi population and will further help to identify strategies to tackle primary microcephaly in the kingdom.

scholarly journals A Novel De Novo Frameshift Mutation in KAT6A Identified by Whole Exome Sequencing

2018 ◽  
Vol 08 (01) ◽  
pp. 010-014 ◽  
Author(s):  
Wafa Alazaizeh ◽  
Asem Alkhateeb
Keyword(s):  
Intellectual Disability ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Frameshift Mutation ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Brain Magnetic Resonance Imaging ◽  
Comparative Genomic ◽  
Feeding Difficulties ◽  
Whole Exome

AbstractIntellectual disability is a common condition with multiple etiologies. The number of monogenic causes has increased steadily in recent years due to the implementation of next generation sequencing. Here, we describe a 2-year-old boy with global developmental delay and intellectual disability. The child had feeding difficulties since birth. He had delayed motor skills and muscular hypotonia. Brain magnetic resonance imaging revealed diffuse white matter loss and thinning of the corpus callosum. Banded karyotype and comparative genomic hybridization (CGH) array were normal. Whole exome sequencing revealed a novel de novo frameshift mutation c.3390delA (p.Lys1130Asnfs*4) in KAT6A gene (NM_006766.4). The heterozygous mutation was confirmed by Sanger sequencing in the patient and its absence in his parents. KAT6A that encodes a histone acetyltransferase has been recently found to be associated with a neurodevelopmental disorder autosomal dominant mental retardation 32 (OMIM: no. 616268). Features of this disorder are nonspecific, which makes it difficult to characterize the condition based on the clinical symptoms alone. Therefore, our findings confirm the utility of whole exome sequencing to quickly and reliably identify the etiology of such conditions.

scholarly journals Whole exome sequencing reveals a biallelic frameshift mutation in GRXCR2 in hearing impairment in Cameroon

2021 ◽  
Author(s):  
Ambroise Wonkam ◽  
Kamogelo Lebeko ◽  
Shaheen Mowla ◽  
Jean Jacques Noubiap ◽  
Mike Chong ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Hearing Impairment ◽  
Whole Exome Sequencing ◽  
Frameshift Mutation ◽  
Whole Exome

scholarly journals Whole-Exome Sequencing Identified a Novel Homozygous Frameshift Mutation of HPS3 in a Consanguineous Family with Hermansky-Pudlak Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Zhao-Xia Wang ◽  
Yi-Hui Liu ◽  
Yi Dong ◽  
Ya-Li Li ◽  
Tie-Yu Tang ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Frameshift Mutation ◽  
Novel Mutation ◽  
Bleeding Diathesis ◽  
Consanguineous Family ◽  
Whole Exome ◽  
The Family ◽  
Hermansky Pudlak Syndrome

Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder with an autosomal recessive inherited pattern. It is mainly characterized by deficiencies in lysosome-related organelles, such as melanosomes and platelet-dense granules, and leads to albinism, visual impairment, nystagmus, and bleeding diathesis. A small number of patients will present with granulomatous colitis or fatal pulmonary fibrosis. At present, mutations in ten known genetic loci (HPS1–11) have been identified to be the genetic cause of HPS. In this study, we enrolled a consanguineous family who presented with typical HPS phenotypes, such as albinism, visual impairment, nystagmus, and bleeding diathesis. Whole-exome sequencing and Sanger sequencing were applied to explore the genetic lesions of the patient. A novel homozygous frameshift mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 was identified and cosegregated in the family members. Furthermore, real-time PCR confirmed that the mutation decreased the expression of HPS3, which has been identified as the disease-causing gene of HPS type 3. According to ACMG guidelines, the novel mutation, resulting in a premature stop codon at amino acid 442, is a pathogenic variant. In summary, we identified a novel mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 in a family with HPS. Our study expanded the variant spectrum of the HPS3 gene and contributed to genetic counseling and prenatal genetic diagnosis of the family.

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