scholarly journals Whole-exome sequencing reveals POLR3B variants associated with progeria-related Wiedemann-Rautenstrauch syndrome

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Shao-Wen Wu ◽  
Lin Li ◽  
Fan Feng ◽  
Li Wang ◽  
Yuan-Yuan Kong ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Postnatal Growth ◽  
Compound Heterozygous ◽  
Congenital Dislocation ◽  
Case Presentation ◽  
Whole Exome ◽  
Compound Heterozygous Variants ◽  
Dislocation Of The Hip

Abstract Background Wiedemann-Rautenstrauch syndrome (WRS) is a rare autosomal recessive neonatal progeroid disorder characterized by prenatal and postnatal growth retardation, short stature, a progeroid appearance, hypotonia, and mental impairment. Case presentation A 6-year-old patient, who initially presented with multiple postnatal abnormalities, facial dysplasia, micrognathia, skull appearance, hallux valgus, and congenital dislocation of the hip, was recruited in this study. The patient was initially diagnosed with progeria. The mother of the patient had abnormal fetal development during her second pregnancy check-up, and the clinical phenotype of the fetus was similar to that of the patient. Whole-exome sequencing (WES) of the patient was performed, and POLR3B compound heterozygous variants—c.2191G > C:p.E731Q and c.3046G > A:p.V1016M—were identified in the patient. Using Sanger sequencing, we found that the phenotypes and genotypes were segregated within the pedigree. These two variants are novel and not found in the gnomAD and 1000 Genomes databases. The two mutation sites are highly conserved between humans and zebrafish. Conclusions Our study not only identified a novel WRS-associated gene, POLR3B, but also broadened the mutational and phenotypic spectra of POLR3B. Furthermore, WES may be useful for identifying rare disease-related genetic variants.

scholarly journals Case Report: Whole Exome Sequencing Identifies Compound Heterozygous Variants in TSFM Gene Causing Juvenile Hypertrophic Cardiomyopathy

2022 ◽  
Vol 8 ◽  
Author(s):  
Jamie O. Yang ◽  
Hapet Shaybekyan ◽  
Yan Zhao ◽  
Xuedong Kang ◽  
Gregory A. Fishbein ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Elongation Factor ◽  
Nuclear Gene ◽  
Compound Heterozygous ◽  
Mitochondrial Translation ◽  
Translation Elongation ◽  
Whole Exome ◽  
Compound Heterozygous Variants

We report a case of hypertrophic cardiomyopathy and lactic acidosis in a 3-year-old female. Cardiac and skeletal muscles biopsies exhibited mitochondrial hyperplasia with decreased complex IV activity. Whole exome sequencing identified compound heterozygous variants, p.Arg333Trp and p.Val119Leu, in TSFM, a nuclear gene that encodes a mitochondrial translation elongation factor, resulting in impaired oxidative phosphorylation and juvenile hypertrophic cardiomyopathy.

Whole-exome sequencing identified compound heterozygous variants in the TTN gene causing Salih myopathy with dilated cardiomyopathy in an Iranian family

2021 ◽  
pp. 1-6
Author(s):  
Mohammad Mahdavi ◽  
Neda Mohsen-Pour ◽  
Majid Maleki ◽  
Mahshid Hesami ◽  
Niloofar Naderi ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Molecular Diagnostic ◽  
Metabolic Parameter ◽  
Compound Heterozygous ◽  
Formidable Challenge ◽  
Whole Exome ◽  
Iranian Family ◽  
Compound Heterozygous Variants

Abstract Background: Salih myopathy, characterised by both congenital myopathy and fatal dilated cardiomyopathy, is an inherited muscle disorder that affects skeletal and cardiac muscles. TTN has been identified as the main cause of this myopathy, the enormous size of this gene poses a formidable challenge to molecular genetic diagnostics. Method: In the present study, whole-exome sequencing, cardiac MRI, and metabolic parameter assessment were performed to investigate the genetic causes of Salih myopathy in a consanguineous Iranian family who presented with titinopathy involving both skeletal and heart muscles in an autosomal recessive inheritance pattern. Results: Two missense variants of TTN gene (NM_001267550.2), namely c.61280A>C (p. Gln20427Pro) and c.54970G>A (p. Gly18324Ser), were detected and segregations were confirmed by polymerase chain reaction-based Sanger sequencing. Conclusions: The compound heterozygous variants, c.61280A>C, (p. Gln20427Pro) and c.54970G>A, (p. Gly18324Ser) in the TTN gene appear to be the cause of Salih myopathy and dilated cardiomyopathy in the family presented. Whole-exome sequencing is an effective molecular diagnostic tool to identify the causative genetic variants of large genes such as TTN.

3-M syndrome – a primordial short stature disorder with novel CUL7 mutation in two Indian patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Radha Rama Devi Akella
Keyword(s):  
Short Stature ◽  
Autosomal Recessive ◽  
Genetic Diagnosis ◽  
Autosomal Recessive Disorder ◽  
Missense Variant ◽  
Postnatal Growth ◽  
Compound Heterozygous ◽  
Case Presentation ◽  
Whole Exome ◽  
Heterozygous Variant

Abstract Objective To evaluate the cause of short stature in children. Case presentation Two children with suspected skeletal dysplasia and short stature were evaluated. Conclusions The 3-M syndrome is a primordial growth disorder manifesting severe postnatal growth restriction, skeletal anomalies and prominent fleshy heels. The 3-M syndrome is a genetically heterogeneous disorder and the phenotype is similar. This is a rare autosomal recessive disorder with normal intellect. Two affected children have been identified by whole-exome sequencing. One patient harboured a compound heterozygous variant and the other was a homozygous missense variant. The genetic diagnosis helped in counselling the families and facilitated prenatal diagnosis in one (case 1) family.

scholarly journals Whole exome sequencing of a patient with suspected mitochondrial myopathy reveals novel compound heterozygous variants in RYR1

2017 ◽  
Vol 5 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Patrick R. Blackburn ◽  
Duygu Selcen ◽  
Jennifer M. Gass ◽  
Jessica L. Jackson ◽  
Sarah Macklin ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Mitochondrial Myopathy ◽  
Compound Heterozygous ◽  
Whole Exome ◽  
Compound Heterozygous Variants

scholarly journals Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hosneara Akter ◽  
Mohammad Shahnoor Hossain ◽  
Nushrat Jahan Dity ◽  
Md. Atikur Rahaman ◽  
K. M. Furkan Uddin ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Diseases ◽  
Leigh Syndrome ◽  
Genetic Profile ◽  
Compound Heterozygous ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Rare Genetic Diseases ◽  
Compound Heterozygous Variants

AbstractCollectively, rare genetic diseases affect a significant number of individuals worldwide. In this study, we have conducted whole-exome sequencing (WES) and identified underlying pathogenic or likely pathogenic variants in five children with rare genetic diseases. We present evidence for disease-causing autosomal recessive variants in a range of disease-associated genes such as DHH-associated 46,XY gonadal dysgenesis (GD) or 46,XY sex reversal 7, GNPTAB-associated mucolipidosis II alpha/beta (ML II), BBS1-associated Bardet–Biedl Syndrome (BBS), SURF1-associated Leigh Syndrome (LS) and AP4B1-associated spastic paraplegia-47 (SPG47) in unrelated affected members from Bangladesh. Our analysis pipeline detected three homozygous mutations, including a novel c. 863 G > C (p.Pro288Arg) variant in DHH, and two compound heterozygous variants, including two novel variants: c.2972dupT (p.Met991Ilefs*) in GNPTAB and c.229 G > C (p.Gly77Arg) in SURF1. All mutations were validated by Sanger sequencing. Collectively, this study adds to the genetic heterogeneity of rare genetic diseases and is the first report elucidating the genetic profile of (consanguineous and nonconsanguineous) rare genetic diseases in the Bangladesh population.

scholarly journals Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhen Zhang ◽  
Ti-Long Huang ◽  
Jing Ma ◽  
Wen-Ji He ◽  
Huaiyu Gu
Keyword(s):  
Ethnic Minority ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Chinese Population ◽  
Novel Mutation ◽  
Genetic Disorders ◽  
Central Nervous System Involvement ◽  
Compound Heterozygous ◽  
Case Presentation ◽  
Whole Exome

Abstract Background PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans. The mutations of PMM2-CDG might lead to the loss of PMM2, which is responsible for the conversion of mannose 6- phosphate into mannose 1-phosphate. Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy. The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy. Now, over 100 new CDG cases have been reported. However, each type of CDG is very rare, and CDGs are problematic to diagnose. In addition, few CDGs have been reported in the Chinese population. Case presentation Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders. Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241–242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2. Two mutations were found in proband and her sibling by whole-exome sequencing. The mutations were identified in this family by Sanger sequencing and no mutations were detected in the normal control. Conclusions This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.

scholarly journals Exome Sequencing Identifies Compound Heterozygous Mutations inSCN5AAssociated with Congenital Complete Heart Block in the Thai Population

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Chuphong Thongnak ◽  
Pornprot Limprasert ◽  
Duangkamol Tangviriyapaiboon ◽  
Suchaya Silvilairat ◽  
Apichaya Puangpetch ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Heart Block ◽  
Complete Heart Block ◽  
Family Members ◽  
Compound Heterozygous ◽  
Affected Child ◽  
Whole Exome ◽  
Congenital Complete Heart Block ◽  
Compound Heterozygous Variants

Background. Congenital heart block is characterized by blockage of electrical impulses from the atrioventricular node (AV node) to the ventricles. This blockage can be caused by ion channel impairment that is the result of genetic variation. This study aimed to investigate the possible causative variants in a Thai family with complete heart block by using whole exome sequencing.Methods. Genomic DNA was collected from a family consisting of five family members in three generations in which one of three children in generation III had complete heart block. Whole exome sequencing was performed on one complete heart block affected child and one unaffected sibling. Bioinformatics was used to identify annotated and filtered variants. Candidate variants were validated and the segregation analysis of other family members was performed.Results. This study identified compound heterozygous variants, c.101G>A and c.3832G>A, in theSCN5Agene and c.28730C>T in theTTNgene.Conclusions. Compound heterozygous variants in theSCN5Agene were found in the complete heart block affected child but these two variants were found only in the this affected sibling and were not found in other unaffected family members. Hence, these variants in theSCN5Agene were the most possible disease-causing variants in this family.

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