Identification of a novel splice site HSPG2 mutation and prenatal diagnosis in Schwartz Jampel Syndrome type 1 using whole exome sequencing

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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Whole exome sequencing diagnoses the first fetal case of Bainbridge-Ropers syndrome presenting as pontocerebellar hypoplasia type 1

Birth Defects Research ◽

10.1002/bdr2.1191 ◽

2018 ◽

Vol 110 (6) ◽

pp. 538-542 ◽

Cited By ~ 5

Author(s):

Séverine Bacrot ◽

Charlotte Mechler ◽

Naima Talhi ◽

Dominique Martin-Coignard ◽

Philippe Roth ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Pontocerebellar Hypoplasia ◽

Whole Exome

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Case report: targeted whole exome sequencing enables the first prenatal diagnosis of the lethal skeletal dysplasia Osteocraniostenosis

BMC Medical Genetics ◽

10.1186/s12881-019-0939-z ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Lara Pemberton ◽

Robert Barker ◽

Anna Cockell ◽

Vijaya Ramachandran ◽

Andrea Haworth ◽

...

Keyword(s):

Case Report ◽

Prenatal Diagnosis ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Skeletal Dysplasia ◽

Genetic Disorder ◽

Specific Gene ◽

Ultrasound Images ◽

Whole Exome ◽

Lethal Skeletal Dysplasia

Abstract Background Osteocraniostenosis (OCS) is a rare genetic disorder characterised by premature closure of cranial sutures, gracile bones and perinatal lethality. Previously, diagnosis has only been possible postnatally on clinical and radiological features. This study describes the first prenatal diagnosis of OCS. Case presentation In this case prenatal ultrasound images were suggestive of a serious but non-lethal skeletal dysplasia. Due to the uncertain prognosis the parents were offered Whole Exome Sequencing (WES), which identified a specific gene mutation in the FAMIIIa gene. This mutation had previously been detected in two cases and was lethal in both perinatally. This established the diagnosis, a clear prognosis and allowed informed parental choice regarding ongoing pregnancy management. Conclusions This case report supports the use of targeted WES prenatally to confirm the underlying cause and prognosis of sonographically suspected abnormalities.

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Identification of a novel ALMS1 pathogenic variant in a family with Cone-Rod Dystrophy using whole exome sequencing, followed by prenatal diagnosis

Meta Gene ◽

10.1016/j.mgene.2018.06.006 ◽

2018 ◽

Vol 17 ◽

pp. 167-171 ◽

Cited By ~ 1

Author(s):

Maryam Rafati ◽

Seyedeh Zahra Tara ◽

Fatemeh Hoseininasab ◽

Saeed Reza Ghaffari

Keyword(s):

Prenatal Diagnosis ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Pathogenic Variant ◽

Whole Exome

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Case report of ascending colon cancer and multiple jejunal GISTs in a patient with neurofibromatosis type 1 (NF1)

BMC Cancer ◽

10.1186/s12885-019-6375-9 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Liang Shang ◽

Zhen Fang ◽

Jin Liu ◽

Fengying Du ◽

Haiyan Jing ◽

...

Keyword(s):

Colon Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Ascending Colon ◽

Malignant Tumours ◽

Whole Exome ◽

Ascending Colon Cancer

Abstract Background NF1(Neurofibromatosis type 1) is an autosomal dominant genetic disorder. Patients with NF1 have an increased risk of developing benign or malignant tumours, such as gastrointestinal stromal tumours (GISTs). However, the coexistence of NF1, GIST and colon cancer is very rare, and few cases have been reported in the literature. Case presentation We admitted a case of a 64-year-old man with type 1 neurofibromatosis, GISTs, and ascending colon cancer. This case was characterized by café-au-lait macules, discrete cutaneous neurofibromas, nodular neurofibromas, multiple jejunal tumours, and ascending colon cancer. Laparoscopic exploration revealed ascending colon cancer and multiple jejunal tumours. Laparoscopic right hemicolectomy and local excision of the jejunal tumours were performed successfully. The pathological results confirmed moderate differentiated adenocarcinoma of the ascending colon with multiple jejunal GISTs (low risk, very low risk). Moreover, the immunohistochemistry results of multiple jejunal GISTs suggest that NF1 is positive. Whole-exome sequencing (WES) of colon cancer revealed mutations in more than 20 genes, including KRAS, PIK3CA, APC, SMAD4, etc. The results of whole-exome sequencing (WES) of jejunal GISTs revealed an NF1 mutation and no KIT or PDGFR gene mutation. Conclusion We report a rare case of simultaneous NF1, GIST and colon adenocarcinoma. For patients with NF1, benign and/or malignant tumours are often combined. Therefore, these patients should undergo regular physical examinations so that early detection and early treatment can be achieved.

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