Whole exome sequencing identifies a novel splice-site mutation in IMPG2 gene causing Stargardt-like juvenile macular dystrophy in a north Indian family

Abstract Background: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare congenital heart defect (CHD), genetics defects have been found in patients with LVNC and their family members; and MYH7 is the most common genetic associated with LVNC. Methods: A trio (fetus and the parents) whole-exome sequencing (WES) was performed when the fetus was found with Ebstein's anomaly (EA), heart dilatation, perimembranous ventricular septal defects (VSD), mild seroperitoneum and single umbilical artery (SUA).Results: Whole-exome sequencing identified a maternal inherited heterozygous splice site mutation in MYH7 (NM_000257.3:c.732+1G>A). Subsequent Sanger sequencing confirmed that the mutation was heterozygous in the fetus, the old sister, the grandmother, and the mother. QPCR experiment using RNA from blood lymphocytes but were unable to amplify any product.Conclusion: This familial case underlines that the striking cardiac phenotypic of MYH7 mutation (the c.732+1G>A spice site variant) may be highly variable. The mechanistic studies which could uncover candidate genes modulating cardiac phenotype associated with LVNC/EA should be proceed.

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Novel splice-site mutation inWDR62revealed by whole-exome sequencing in a Sudanese family with primary microcephaly

Congenital Anomalies ◽

10.1111/cga.12144 ◽

2016 ◽

Vol 56 (3) ◽

pp. 135-137 ◽

Cited By ~ 6

Author(s):

Fatma Bastaki ◽

Madiha Mohamed ◽

Pratibha Nair ◽

Fatima Saif ◽

Nafisa Tawfiq ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Splice Site ◽

Splice Site Mutation ◽

Primary Microcephaly ◽

Site Mutation ◽

Whole Exome

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Whole-exome sequencing identifies a homozygous donor splice-site mutation inSTAG3that causes primary ovarian insufficiency

Clinical Genetics ◽

10.1111/cge.13034 ◽

2017 ◽

Vol 93 (2) ◽

pp. 340-344 ◽

Cited By ~ 14

Author(s):

W.-B. He ◽

S. Banerjee ◽

L.-L. Meng ◽

J. Du ◽

F. Gong ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Splice Site ◽

Splice Site Mutation ◽

Primary Ovarian Insufficiency ◽

Donor Splice Site ◽

Site Mutation ◽

Ovarian Insufficiency ◽

Donor Splice ◽

Whole Exome

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Germline whole exome sequencing of a family with appendiceal mucinous tumours presenting with pseudomyxoma peritonei

10.21203/rs.2.15420/v1 ◽

2019 ◽

Author(s):

Mei Sim Lung ◽

Catherine A. Mitchell ◽

Maria A. Doyle ◽

Andrew C. Lynch ◽

Kylie L. Gorringe ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Splice Site ◽

Pseudomyxoma Peritonei ◽

Loss Of Function ◽

Site Mutation ◽

Germline Variants ◽

Missense Variants ◽

Whole Exome ◽

Mucinous Tumours

Abstract Background Familial cases of appendiceal mucinous tumours (AMTs) are extremely rare and the underlying genetic aetiology uncertain. We identified potential predisposing germline genetic variants in a father and daughter with AMTs presenting with pseudomyxoma peritonei (PMP) and correlated these with regions of loss of heterozygosity (LOH) in the tumours. Materials and Methods Through germline whole exome sequencing, we identified novel heterozygous loss-of-function (LoF) (i.e. nonsense, frameshift and essential splice site mutations) and missense variants shared between father and daughter, and validated all LoF variants, and missense variants with a Combined Annotation Dependent Depletion (CADD) scaled score of ≥10. Genome-wide copy number analysis was performed on tumour tissue from both individuals to identify regions of LOH. Results Seventeen novel variants in 17 genes were shared by the father and daughter: a nonsense mutation in REEP5 , an essential splice site mutation in THOP1 , and 15 missense variants. None of these germline variants were located in tumour regions of LOH shared by the father and daughter. Four genes ( EXOG , RANBP2, RANBP6 and TNFRSF1B ) harboured missense variants that fell in a region of LOH in the tumour from the father only, but none showed somatic loss of the wild type allele in the tumour. The REEP5 gene was sequenced in 23 individuals with presumed sporadic PMP; no LoF or rare missense germline variants were identified. Conclusion Germline exome sequencing of a father and daughter with AMTs identified novel candidate predisposing genes. Further studies are required to clarify the role of these genes in familial AMTs.

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Identification of Novel TTN Mutations in Three Chinese Familial Dilated Cardiomyopathy Pedigrees by Whole Exome Sequencing

Cardiovascular Innovations and Applications ◽

10.15212/cvia.2019.0579 ◽

2020 ◽

Vol 4 (4) ◽

pp. 229-237

Author(s):

Ying Peng ◽

Jinxin Miao ◽

Yafei Zhai ◽

Guangming Fang ◽

Chuchu Wang ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Clinical Symptoms ◽

Splice Site Mutation ◽

Site Mutation ◽

Chinese Families ◽

Familial Dilated Cardiomyopathy ◽

Whole Exome ◽

The Relationship

Familial dilated cardiomyopathy (DCM) is associated with numerous genes, especially those of the sarcomere family. The titin gene (TTN) consists of 365 exons and encodes the largest sarcomere protein (titin) in our bodies. Titin is associated with many diseases, such as hypertrophic cardiomyopathy and DCM. Here we screened three Chinese families affected by DCM, and found that each harbors a stop-gain or splice site mutation in TTN (c.G20137T,c. G52522T,c.44610-2A>C). Assessment of the probands by electrocardiogram, B-mode echocardiography, and cardiac magnetic resonance imaging revealed impaired cardiac function, arrhythmia, or abnormal cardiac structure. In conclusion, using whole exome sequencing, we found three unreported TTN mutations associated with DCM. This has expanded the TTN mutation spectrum of Chinese DCM patients, especially in Henan, the most populous province. These data provide new genetic targets for the diagnosis and treatment of DCM, and will increase our understanding of the relationship between TTN mutation and DCM clinical symptoms.

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

10.21203/rs.3.rs-770260/v1 ◽

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.

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