scholarly journals Prenatal diagnosis of feta noncompaction cardiomyopathy with de novo CALM2 mutation

2021 ◽  
Author(s):  
wen zhang ◽  
xiaohui dai ◽  
Hanmin Liu ◽  
Lei Li ◽  
Shu Zhou ◽  
...  
Keyword(s):  
Case Report ◽  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Genomic Dna ◽  
De Novo ◽  
Heterozygous Mutation ◽  
Histopathologic Examination ◽  
Noncompaction Cardiomyopathy ◽  
First Case ◽  
Whole Exome

We report what apprears to be the first case of fetal noncompaction cardiomyopathy in both ventricles accompanied by a mutation in the calmodulin gene (CALM2): A 25-year-old woman was referred to our hospital at 25+1 weeks of gestation for evaluation of fetal defects. A postnatal echocardiography showed biventricular noncompaction cardiomyopathy. After terminated the pregnancy, fetal noncompaction cardiomyopathy was comfirmed by autopsy and histopathologic examination. And the whole-exome sequencing of genomic DNA demonstrated a de novo heterozygous mutation (c.389A>G;p.D130G) in CALM2, whereas the parents were normal. In this case report, we highlight the gene mutation in noncompaction cardiomyopathy.

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

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.

scholarly journals A Novel Frameshift Mutation in KAT6A Is Associated with Pancraniosynostosis

2020 ◽  
Author(s):  
Fady P. Marji ◽  
Jennifer A. Hall ◽  
Erin Anstadt ◽  
Suneeta Madan-Khetarpal ◽  
Jesse A. Goldstein ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Frameshift Mutation ◽  
De Novo ◽  
Cranial Sutures ◽  
Speech Delay ◽  
First Case ◽  
Whole Exome ◽  
Suture Fusion

AbstractDe novo heterozygous mutations in the KAT6A gene give rise to a distinct intellectual disability syndrome, with features including speech delay, cardiac anomalies, craniofacial dysmorphisms, and craniosynostosis. Here, we reported a 16-year-old girl with a novel pathogenic variant of the KAT6A gene. She is the first case to possess pancraniosynostosis, a rare suture fusion pattern, affecting all her major cranial sutures. The diagnosis of KAT6A syndrome is established via recognition of its inherent phenotypic features and the utilization of whole exome sequencing. Thorough craniofacial evaluation is imperative, craniosynostosis may require operative intervention, the delay of which may be detrimental.

A De novo Loss-of-Function Mutation in PAFAH1B1 Identified in a Single Case with Agyria–Pachygyria Complex

2019 ◽  
Vol 18 (01) ◽  
pp. 033-038
Author(s):  
Yali Ou ◽  
Bingwu Xiang ◽  
Liu Yang ◽  
Wei Chen ◽  
Xiang Chen ◽  
...  
Keyword(s):  
De Novo ◽  
Single Case ◽  
Bioinformatic Analysis ◽  
Heterozygous Mutation ◽  
Loss Of Function ◽  
Speech Impairment ◽  
Affected Child ◽  
Neuropsychological Disorders ◽  
First Case ◽  
Whole Exome

AbstractTo identify genetic causes in affected infants with abnormalities of brain development, including malformations of cortical development–associated neuropsychological disorders, affected infants were recruited based on their clinical examination and cranial imaging studies. Trio whole-exome sequencing (WES), bioinformatic analysis, and genotype–phenotype correlations were performed for 20 affected subjects to identify candidate mutations, followed by Sanger sequencing for further verification. In the present study, we identified a de novo heterozygous mutation (c.265C > T, p.R89*) of the PAFAH1B1 gene in the affected child with epilepsy, speech impairment, and cerebral palsy. The mutation was predicted to be a null loss-of-function allele, which was not found in ExAC and the Chinse Han Exome Sequences databases. Magnetic resonance imaging of the brain demonstrated bilateral parieto-occipital and temporal lissencephaly as well as frontal partial pachygyria in the affected child. This is the first case with agyria–pachygyria complex due to a nonsense mutation in the Chinese population identified by a trio WES approach.

scholarly journals OR15-07 Novel Genes Involved in Sex Differentiation Identified by Whole-Exome Sequencing in a Cohort of Children with Disorders of Sex Development

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yardena Tenenbaum Rakover ◽  
Osnat Admoni ◽  
Ghadir Elias Assad ◽  
Shira London ◽  
Marie Noufi Barhoum ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
De Novo Mutation ◽  
Novel Genes ◽  
Sex Development ◽  
First Case ◽  
Whole Exome

Abstract Background: Disorders of sex development (DSD) are classified as a congenital discrepancy between external genitalia, gonadal and chromosomal sex. Despite extensive laboratory and imaging investigations, the etiology of DSD is unknown in more than 50% of patients and the diagnosis is often delayed to the second decade of life. Our objective was to evaluate the etiology of DSD by whole-exome sequencing (WES) in children in whom hormonal and candidate gene approaches had not identified the etiology. Methods: Nine patients diagnosed with DSD (eight 46,XY and one 46,XX) were enrolled. Patients underwent hormonal evaluation, including ACTH, GnRH and hCG tests. Candidate genes were sequenced in accordance with the hormonal results. WES was performed for the probands and their parents. Results: The eight 46,XY patients presented with micropenis, cryptorchidism and hypospadias at birth and the 46,XX patient with fusion of the labia majora. In six of the nine patients (66%), a pathogenic mutation was identified by WES that explained the phenotype: four known DSD-causing genes—POR, CHD7, HSD17B3 and WT1—and two novel genes—BMP4 and RFXP2. In three patients, variants of unknown significance were found. An 11-y-old boy had a novel de-novo mutation in BMP4. In humans, mutations in this gene, encoding bone morphogenetic protein 4, are associated with autosomal dominant microphthalmia. BMP4 is expressed in the urethral epithelium and has a role in the development of external genitalia and the pituitary. This is the first report of a BMP4 mutation in a child with DSD. A 12-y-old boy had a mutation in RFXP2, encoding insulin-like 3 hormone receptor, which has been previously reported in adult males with cryptorchidism. This is the first case of an RFXP2 mutation in a child with DSD. Conclusions: WES has a crucial role in early diagnosis of the etiology of DSD, making extensive endocrine testing unnecessary, and has important implications for sex of rearing decisions.

scholarly journals Whole exome sequencing for prenatal diagnosis of CHARGE syndrome: a case report

2019 ◽  
Vol 19 (2) ◽  
pp. 125-128
Author(s):  
Irene WY Lok ◽  
CW Kong ◽  
Anita SY Kan ◽  
KS Yeung ◽  
Mullin HC Yu ◽  
...  
Keyword(s):  
Case Report ◽  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Charge Syndrome ◽  
Whole Exome

scholarly journals De novo NIPBL Mutations in Vietnamese Patients with Cornelia de Lange Syndrome

Medicina ◽  
2020 ◽  
Vol 56 (2) ◽  
pp. 76
Author(s):  
Duong Chi Thanh ◽  
Can Thi Bich Ngoc ◽  
Ngoc-Lan Nguyen ◽  
Chi Dung Vu ◽  
Nguyen Van Tung ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
Cornelia De Lange Syndrome ◽  
Heterozygous Mutation ◽  
Body Parts ◽  
Efficient Tool ◽  
Whole Exome ◽  
Cornelia De Lange ◽  
In Silico Analyses

Cornelia de Lange Syndrome (CdLS) is a rare congenital genetic disease causing abnormal unique facial phenotypes, several defects in organs and body parts, and mental disorder or intellectual disorder traits. Main causes of CdLS have been reported as variants in cohesin complex genes, in which mutations in the NIPBL gene have been estimated to account for up to 80%. Our study included three Vietnamese patients with typical CdLS phenotypes. Whole exome sequencing revealed two known heterozygous mutations c.6697G>A (p.Val2233Met) and c.2602C>T (p.Arg868X), and a novel heterozygous mutation c.4504delG (p.Val1502fsX87) in the NIPBL gene of the three patients. In silico analyses of the identified mutations predicted possible damaging and truncating effects on the NIPBL protein. Inherited analyses in the patients’ families showed that all of the mutations are de novo. Our results lead a definitive diagnosis of patients with CdLS and expand the spectrum of mutations in the NIPBL gene. These findings also confirm whole exome sequencing is an efficient tool for genetic screening of CdLS.

Congenital cataract with LSS gene mutations: a new case report

2017 ◽  
Vol 30 (11) ◽  
Author(s):  
Xiaodan Chen ◽  
Li Liu
Keyword(s):  
Case Report ◽  
Exome Sequencing ◽  
Pediatric Patient ◽  
Congenital Cataract ◽  
Gene Mutations ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Case Presentation ◽  
Whole Exome

AbstractBackground:Congenital cataract is one of the major causes of blindness and amblyopia in children. About one-third of the cases are inherited.Case presentation:We applied whole exome sequencing for a pediatric patient with congenital cataract, small penis, baldness and absence of eyebrows and detected a compound heterozygous mutation in the lanosterol synthase (Conclusions:We concluded that the mutations affect the structural stability of the protein to some extent.

scholarly journals Whole-exome sequencing with targeted analysis and epilepsy after acute symptomatic neonatal seizures

2021 ◽  
Author(s):  
Adam L. Numis ◽  
Gilberto da Gente ◽  
Elliott H. Sherr ◽  
Hannah C. Glass
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
List Type ◽  
Sequencing Analysis ◽  
Neonatal Seizures ◽  
Pathogenic Variants ◽  
Targeted Analysis ◽  
Whole Exome ◽  
Epilepsy Gene

Abstract Background The contribution of pathogenic gene variants with development of epilepsy after acute symptomatic neonatal seizures is not known. Methods Case–control study of 20 trios in children with a history of acute symptomatic neonatal seizures: 10 with and 10 without post-neonatal epilepsy. We performed whole-exome sequencing (WES) and identified pathogenic de novo, transmitted, and non-transmitted variants from established and candidate epilepsy association genes and correlated prevalence of these variants with epilepsy outcomes. We performed a sensitivity analysis with genes associated with coronary artery disease (CAD). We analyzed variants throughout the exome to evaluate for differential enrichment of functional properties using exploratory KEGG searches. Results Querying 200 established and candidate epilepsy genes, pathogenic variants were identified in 5 children with post-neonatal epilepsy yet in only 1 child without subsequent epilepsy. There was no difference in the number of trios with non-transmitted pathogenic variants in epilepsy or CAD genes. An exploratory KEGG analysis demonstrated a relative enrichment in cell death pathways in children without subsequent epilepsy. Conclusions In this pilot study, children with epilepsy after acute symptomatic neonatal seizures had a higher prevalence of coding variants with a targeted epilepsy gene sequencing analysis compared to those patients without subsequent epilepsy. Impact We performed whole-exome sequencing (WES) in 20 trios, including 10 children with epilepsy and 10 without epilepsy, both after acute symptomatic neonatal seizures. Children with post-neonatal epilepsy had a higher burden of pathogenic variants in epilepsy-associated genes compared to those without post-neonatal epilepsy. Future studies evaluating this association may lead to a better understanding of the risk of epilepsy after acute symptomatic neonatal seizures and elucidate molecular pathways that are dysregulated after brain injury and implicated in epileptogenesis.

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