scholarly journals Identification of Novel ADGRV1 and KCNC2 Variants Using Whole-Exome Sequencing in Two Colombian Patients with Usher and Encephalopathy Syndromes

2021 ◽  
Author(s):  
Estephania Candelo ◽  
Lorena Diaz-Ordoñez ◽  
Rafael Pacheco ◽  
Emelina Ruiz ◽  
Harry Pachajoa
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Usher Syndrome ◽  
Epileptic Encephalopathy ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Epilepsy Syndrome ◽  
Compound Heterozygous ◽  
Whole Exome ◽  
Excellent Method

Abstract Introduction: Usher syndrome has a broad phenotypic and genotypic spectrum. Developmental and epileptic encephalopathy-52 (DEE52) is a sever autosomal recessive seizure disorder that is characterized by infantile onset of refractory seizures, consequently resulting in delayed global development. This study aimed to describe the clinical features and to investigate the four variants identified in a Colombian family with Usher syndrome and KCNC2 encephalopathy syndrome.Methods and Results: We present a case of a family with two clinically relevant phenotypes: a mother with a compound heterozygous mutation causing Usher Syndrome, type IIC (USH2C) and her 15-year-old son who carried one heterozygous variant in the KCNC2 gene (p.P470S) and two cis mutations (p.V2927I and p.Q4955EfsTer10) in the ADGRV1 gene segregated from his mother, and a second non-disrupted allele. Owing to this, the boy did not present with USH2C but presented a developmental epilepsy syndrome. His younger sibling was unaffected, although he did inherit the trans mutation in a single pathogenic allele from his mother.Discussion and Conclusion: Whole-exome sequencing helps detect genes related to known and novel hearing loss and seizure syndrome. However, familiar segregation studies are an excellent method to clarify genotype-phenotype correlation in families, where multiple genes of clinically relevant have been identified. This method helps determine the genotype-phenotype relationship of a disease, which is associated with the clinical presentation and determines the pathogenicity of variants that are classified as variants of uncertain clinical significance.

scholarly journals Whole-Exome Sequencing Identified a Novel Compound Heterozygous Mutation of LRRC6 in a Chinese Primary Ciliary Dyskinesia Patient

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Lv Liu ◽  
Hong Luo
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Primary Ciliary Dyskinesia ◽  
Premature Stop Codon ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Mrna Levels ◽  
Whole Exome ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a clinical rare peculiar disorder, mainly featured by respiratory infection, tympanitis, nasosinusitis, and male infertility. Previous study demonstrated it is an autosomal recessive disease and by 2017 almost 40 pathologic genes have been identified. Among them are the leucine-rich repeat- (LRR-) containing 6 (LRRC6) codes for a 463-amino-acid cytoplasmic protein, expressed distinctively in motile cilia cells, including the testis cells and the respiratory epithelial cells. In this study, we applied whole-exome sequencing combined with PCD-known genes filtering to explore the genetic lesion of a PCD patient. A novel compound heterozygous mutation in LRRC6 (c.183T>G/p.N61K; c.179-1G>A) was identified and coseparated in this family. The missense mutation (c.183T>G/p.N61K) may lead to a substitution of asparagine by lysine at position 61 in exon 3 of LRRC6. The splice site mutation (c.179-1G>A) may cause a premature stop codon in exon 4 and decrease the mRNA levels of LRRC6. Both mutations were not present in our 200 local controls, dbSNP, and 1000 genomes. Three bioinformatics programs also predicted that both mutations are deleterious. Our study not only further supported the importance of LRRC6 in PCD, but also expanded the spectrum of LRRC6 mutations and will contribute to the genetic diagnosis and counseling of PCD patients.

scholarly journals Rapid Trio Exome Sequencing for Autosomal Recessive Renal Tubular Dysgenesis in Recurrent Oligohydramnios

2021 ◽  
Vol 12 ◽  
Author(s):  
Shin-Yu Lin ◽  
Gwo-Tsann Chuang ◽  
Chien-Hui Hung ◽  
Wei-Chou Lin ◽  
Yung-Ming Jeng ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Neonatal Death ◽  
Autosomal Recessive ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Early Neonatal Death ◽  
Renal Tubular Dysgenesis ◽  
Whole Exome ◽  
Renal Tubular

Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the AGT gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G > T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. AGT gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally.

Utility of whole exome sequencing in the diagnosis of Usher syndrome: Report of novel compound heterozygous MYO7A mutations

2018 ◽  
Vol 108 ◽  
pp. 17-21 ◽  
Author(s):  
Khushnooda Ramzan ◽  
Mohammed Al-Owain ◽  
Rozeena Huma ◽  
Selwa A.F. Al-Hazzaa ◽  
Sarah Al-Ageel ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Usher Syndrome ◽  
Compound Heterozygous ◽  
Whole Exome ◽  
Syndrome Report

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 A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

2021 ◽  
Author(s):  
Qing Li ◽  
Chengfeng Wang ◽  
Wei Li ◽  
Zaiqiang Zhang ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Skin Biopsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Collagen Type Iv ◽  
Lacunar Infarcts ◽  
Whole Exome

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

scholarly journals Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yahya Benbouchta ◽  
Imane Cherkaoui Jaouad ◽  
Habiba Tazi ◽  
Hamza Elorch ◽  
Mouna Ouhenach ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Corneal Dystrophy ◽  
Heterozygous Mutation ◽  
Large Variability ◽  
Whole Exome ◽  
Moroccan Family

Abstract Background Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, noninflammatory bilateral corneal diseases that are usually limited to the cornea. CD is characterized by a large variability in the age of onset, evolution and visual impact and the accumulation of insoluble deposits at different depths in the cornea. Clinical symptoms revealed bilateral multiple superficial, epithelial, and stromal anterior granular opacities in different stages of severity among three patients of this family. A total of 99 genes are involved in CDs. The aim of this study was to identify pathogenic variants causing atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with severely different stages of evolution. Case presentation In this study, we report a large Moroccan family with CD. Whole-exome sequencing (WES) was performed in the three affected members who shared a phenotype of corneal dystrophy in different stages of severity. Variant validation and familial segregation were performed by Sanger sequencing in affected sisters and mothers and in two unaffected brothers. Whole-exome sequencing showed a novel heterozygous mutation (c.1772C > A; p.Ser591Tyr) in the TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities in different stages of severity among three patients in this family. Conclusions This report describes a novel mutation in the TGFBI gene found in three family members affected by different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy; therefore, it could be considered a novel phenotype genotype correlation, which will help in genetic counselling for this family.

RHOBTB2 p.Arg511Trp Mutation in Early Infantile Epileptic Encephalopathy-64: Review and Case Report

2021 ◽  
Author(s):  
J Fonseca ◽  
C Melo ◽  
C Ferreira ◽  
M Sampaio ◽  
R Sousa ◽  
...  
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Status Epilepticus ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Epileptic Encephalopathy ◽  
Btb Domain ◽  
Pathogenic Variants ◽  
Severe Intellectual Disability ◽  
Whole Exome

AbstractEarly infantile epileptic encephalopathy-64 (EIEE 64), also called RHOBTB2-related developmental and epileptic encephalopathy (DEE), is caused by heterozygous pathogenic variants (EIEE 64; MIM#618004) in the Rho-related BTB domain-containing protein 2 (RHOBTB2) gene. To date, only 13 cases with RHOBTB2-related DEE have been reported. We add to the literature the 14th case of EIEE 64, identified by whole exome sequencing, caused by a heterozygous pathogenic variant in RHOBTB2 (c.1531C > T), p.Arg511Trp. This additional case supports the main features of RHOBTB2-related DEE: infantile-onset seizures, severe intellectual disability, impaired motor functions, postnatal microcephaly, recurrent status epilepticus, and hemiparesis after seizures.

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