scholarly journals Whole-Exome Sequencing Identifies an Intronic Cryptic Splice Site in SERPINF1 Causing Osteogenesis Imperfecta Type VI

JBMR Plus ◽  
2018 ◽  
Vol 2 (4) ◽  
pp. 235-239 ◽  
Author(s):  
Zixue Jin ◽  
Lindsay C Burrage ◽  
Ming-Ming Jiang ◽  
Yi-Chien Lee ◽  
Terry Bertin ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Splice Site ◽  
Osteogenesis Imperfecta Type ◽  
Cryptic Splice Site ◽  
Whole Exome

scholarly journals Striking Cardiac Phenotypic Variability in A Chinese Family With A MYH7 Splice Site Mutation

2021 ◽  
Author(s):  
Peng Tu ◽  
Hairui Sun ◽  
Xiaohang Zhang ◽  
Qian Ran ◽  
suzhen Ran ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Splice Site ◽  
Phenotypic Variability ◽  
Splice Site Mutation ◽  
Left Ventricular ◽  
Chinese Family ◽  
Site Mutation ◽  
Cardiac Phenotype ◽  
Whole Exome

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.

scholarly journals Whole Exome Sequencing Reveals Novel PHEX Splice Site Mutations in Patients with Hypophosphatemic Rickets

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130729 ◽  
Author(s):  
Sara L. Ma ◽  
Virginia Vega-Warner ◽  
Christopher Gillies ◽  
Matthew G. Sampson ◽  
Vijay Kher ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Splice Site ◽  
Hypophosphatemic Rickets ◽  
Whole Exome

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

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.

scholarly journals Whole-exome sequencing identifies de novo mutation in the COL1A1 gene to underlie the severe osteogenesis imperfecta

2015 ◽  
Vol 9 (1) ◽  
Author(s):  
Katre Maasalu ◽  
Tiit Nikopensius ◽  
Sulev Kõks ◽  
Margit Nõukas ◽  
Mart Kals ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
De Novo Mutation ◽  
Col1a1 Gene ◽  
Whole Exome

Whole exome sequencing reveals a mutation in an osteogenesis imperfecta patient

Meta Gene ◽  
2017 ◽  
Vol 11 ◽  
pp. 137-140 ◽  
Author(s):  
Mehmet Ali Ergun ◽  
Gamze Bilgili ◽  
Uğur Hamurcu ◽  
Atila Ertan
Keyword(s):  
Osteogenesis Imperfecta ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Osteogenesis Imperfecta Patient ◽  
Whole Exome

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

2016 ◽  
Vol 56 (3) ◽  
pp. 135-137 ◽  
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

scholarly journals Osteogenesis Imperfecta With Cerebral Atherosclerosis: A Family Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A209-A209
Author(s):  
Junyu He ◽  
Zhihong Liao
Keyword(s):  
Osteogenesis Imperfecta ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Manifestation ◽  
Family Members ◽  
Whole Exome ◽  
The Family ◽  
Col1a2 Gene ◽  
History Of ◽  
Severe Fracture

Abstract Background: Osteogenesis imperfecta (OI) is a rare hereditary connective tissue disease. It is mainly associated with pathogenic variants in COL1A1 or COL1A2. Patients with OI usually have repeated history of bone fractures. Besides, osteogenesis imperfecta is associated with some cardiovascular complications, such as aortic and mitral valve dysfunction, aneurysm and aortic dissection. But the relationship between these diseases has not been well studied. Case Presentation: A 55-year-old man was admitted to our hospital mainly due to “dizziness for 2 hours”. He had a 4-month history of hypertension and a history of smoking for more than 20 years. He had no history of drinking alcohol. He had hunchback and O-type legs. Besides, the patient and some of his relatives had a history of repeated brittle fractures,which was considered as “osteogenesis imperfecta”. The clinical manifestation of OI in this family varies to a certain extent, from simple tooth disintegration to severe fracture deformity. The most serious patient of his family was unable to walk. CT and MRI revealed multiple systemic arteriosclerosis, including vertebral artery, posterior inferior cerebellar artery, cervical artery, and bilateral cerebellar multiple lacunar cerebral infarction. The blood sample of the patient was tested by whole exome sequencing, and the saliva samples of the patient’s family members were tested by Sanger sequencing. A mutation c.3159 + 2T > A was detected in COL1A2 gene associated with OI, also found in the other affected family members, which had not been reported before. It was a segregating mutation in the family. The clinical severity of the family members was heterogeneous. Discussion: This case is worth learning from the following aspects: 1. A pathogenic heterozygous mutation, c.3159 + 2T > A was detected in COL1A2 gene in the patient with OI, which is not reported in previous cases of OI. 2. The clinical manifestation of OI in this family varies to a certain extent, from simple tooth disintegration to severe fracture deformity. The most serious patient of his family was unable to walk. It presented the clinical heterogeneity of OI. Further basic researh on the mutation site of related gene of OI are needed. 3. We found the possibility of developing cerebral atherosclerosis in patients with OI. Therefore, patients with OI should give up smooking, exercise properly and keep on a low fat diet. They should pay attention to control blood pressure and blood lipid so as to reduce the risk of atherosclerosis. Conclusion: A c.3159 + 2T>A mutation in COL1A2 gene detected by whole exome sequencing was the causing reason of OI, the discovery enriched the gene mutation spectrum of OI. We also found that OI may have relationship with premature atherosclerosis, and the abnormal bones of the cervical spine may lead to vertebrobasilar ischemia.

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