scholarly journals Clinical and genetic characteristics of distal arthrogryposis caused by mutations in the PIEZO2 gene

2021 ◽  
Vol 11 (2) ◽  
pp. 48-55
Author(s):  
T. V. Markova ◽  
E. L. Dadali ◽  
S. S. Nikitin ◽  
A.  F . Murtazina ◽  
O. L. Mironovich ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Terminal Region ◽  
De Novo Mutation ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Distal Arthrogryposis ◽  
Genetic Characteristics ◽  
Reading Frame ◽  
The Third ◽  
Compound Heterozygous State

Mutations in the PIEZO2 gene, which is involved in the formation of the mechanosensitive cation channel Piezo2, can cause distal arthrogryposis type 3 (Gordon’s syndrome), type 5, and Marden–Walker syndrome. Clinical and genetic characteristics of two patients with distal arthrogryposis with autosomal dominant inheritance and one with autosomal recessive inheritance are presented. Exome sequencing in one case revealed a de novo mutation in exon 52 of the PIEZO2gene c.8238G>A (p.Trp2746*, NM_022068.3), in the second, a known deletion of three nucleotides in exon 52 of the PIEZO2 gene c.8181_8183delAGA (p Glu2727del, NM_022068.3) was found, in the third, two mutations in the compound heterozygous state – a deletion of four nucleotides leading to a shift in the reading frame in c.1863_1866delTCAG(p.Ser621fs, NM_022068) and a deletion with putative coordinates 10785050–10789339 bp, spanning 15–16 exons of the PIEZO2 gene (NM_022068; LOD 2.40). The third patient was found to have two newly detected mutations in the compound heterozygous state – a deletion of four nucleotides, leading to a shift in the reading frame in exon 14, p.1863_1866delTCAG (p.Ser621fs, NM_022068) and a deletion with assumed coordinates 10785050–10789339 b. o., (NM_022068; LOD 2.40), spanning 15–16 exons of the PIEZO2 gene. The previous assumption was confirmed that heterozygous mutations are more often localized in exon 52 of the PIEZO2 gene and disrupt the amino acid sequence of the C‑terminal region of the protein molecule, while in patients with an autosomal recessive mode of inheritance of the mutation, the N‑terminal region is more often found.

scholarly journals Compound heterozygous variants in the ABCG8 gene in a Japanese girl with sitosterolemia

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Nobuhiro Hashimoto ◽  
Sumito Dateki ◽  
Eri Suzuki ◽  
Takatoshi Tsuchihashi ◽  
Aiko Isobe ◽  
...  
Keyword(s):  
Plant Sterol ◽  
Autosomal Recessive ◽  
Elevated Serum ◽  
Asian Population ◽  
Autosomal Recessive Disorder ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Single Nucleotide ◽  
Compound Heterozygous Variants ◽  
Compound Heterozygous State

AbstractSitosterolemia is an autosomal recessive disorder that affects lipid metabolism and is characterized by elevated serum plant sterol levels, xanthomas, and accelerated atherosclerosis. In this study, we report a novel nonsense single-nucleotide variant, c.225G > A (p.Trp75*), and an East Asian population-specific missense multiple-nucleotide variant, c.1256_1257delTCinsAA (p.Ile419Lys), in the ABCG8 gene in a compound heterozygous state observed in a Japanese girl with sitosterolemia.

scholarly journals CLINICAL-GENETIC FEATURES OF THE KNOBLOCH SYNDROME IN THE RUSSIAN FAMILY

2018 ◽  
Vol 13 (2) ◽  
pp. 109-112
Author(s):  
Olga V. Khlebnikova ◽  
E. L Dadali ◽  
L. A Bessonova ◽  
F. A Konovalov
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Clinical Genetic ◽  
Central Nervous System Damage ◽  
Genetic Characteristics ◽  
Knobloch Syndrome ◽  
Genetic Features ◽  
Compound Heterozygous State

The article presents the clinical and genetic characteristics of a patient with Knobloch syndrome caused by the previously indescried combination of mutations in the compound heterozygous state c.4054_4055delCT / c.1469-2A>G in the gene COL18A1. The peculiarity of the presented case is the absence of symptoms of central nervous system damage, found in most patients with this syndrome.

scholarly journals Progressive Early-Onset Leukodystrophy Related to Biallelic Variants in the KARS Gene: The First Case Described in Latin America

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1437
Author(s):  
Adriana Vargas ◽  
Jorge Rojas ◽  
Ivan Aivasovsky ◽  
Sergio Vergara ◽  
Marianna Castellanos ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Gene Mutations ◽  
Mitochondrial Respiratory Chain ◽  
Trna Synthetase ◽  
Transfer Rna ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Aminoacyl Trna Synthetase ◽  
First Case ◽  
Compound Heterozygous State

The KARS gene encodes the aminoacyl-tRNA synthetase (aaRS), which activates and joins lysine with its corresponding transfer RNA (tRNA) through the ATP-dependent aminoacylation of the amino acid. KARS gene mutations have been linked to diverse neurologic phenotypes, such as neurosensorial hearing loss, leukodystrophy, microcephaly, developmental delay or regression, peripheral neuropathy, cardiomyopathy, the impairment of the mitochondrial respiratory chain, and hyperlactatemia, among others. This article presents the case of a Colombian pediatric patient with two pathological missense variants in a compound heterozygous state in the KARS gene and, in addition to the case report, the paper reviews the literature for other cases of KARS1-associated leukodystrophy.

Progressive Early Onset Leukodystrophy Related to Biallelic Variants in the KARS Gene: The First Case Described in Latin America

2020 ◽  
Author(s):  
Adriana Vargas-Niño ◽  
Jorge Rojas-Martinez ◽  
Ivan Aivasovsky-Trotta ◽  
Sergio Vergara-Cardenas ◽  
Marianna Castellanos-Fernandez ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Gene Mutations ◽  
Mitochondrial Respiratory Chain ◽  
Trna Synthetase ◽  
Transfer Rna ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Aminoacyl Trna Synthetase ◽  
First Case ◽  
Compound Heterozygous State

The KARS gene encodes the aminoacyl-tRNA synthetase (aaRS) which activates and joins the lysin with its corresponding transfer RNA (tRNA), through the ATP-dependent aminoacylation of the amino acid. The KARS gene mutations have been linked to diverse neurologic phenotypes such as: neurosensorial hearing loss, leukodistrophy, microcephaly, developmental delay or regression, peripheral neuropathy, cardiomyopathy, impairment of the mitochondrial respiratory chain, hyperlactatemia, among others. This article presents the case of a Colombian pediatric patient with two pathological missense variants in a compound heterozygous state in the KARS gene.

Phenotypic expression of a novel C282Y/R226G compound heterozygous state in HFE hemochromatosis: Molecular dynamics and biochemical studies

2014 ◽  
Vol 52 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Christine Cézard ◽  
Amrathlal Rabbind Singh ◽  
Gérald Le Gac ◽  
Isabelle Gourlaouen ◽  
Claude Ferec ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Phenotypic Expression ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Biochemical Studies ◽  
Compound Heterozygous State

scholarly journals Audiological features in Serbian patients with hearing impairment identified with c.35delG in the GJB2 gene

2021 ◽  
pp. 98-98
Author(s):  
Bojana Dobric ◽  
Danijela Radivojevic ◽  
Jovana Jecmenica ◽  
Vassos Neocleous ◽  
Pavlos Fanis ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Autosomal Recessive ◽  
Gjb2 Gene ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Phenotype Correlation ◽  
Pathogenic Variants ◽  
Environmental Causes ◽  
35Delg Mutation

Introduction/Objective. Hearing impairment (HI) is the most common sensorineural disorder with an incidence of 1/700-1000 newborns. Variants in the GJB2 gene are the major cause of autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL). The degree of HI in patients with detected mutations in GJB2 gene ranges from mild to profound. The aim of this study was to determine possible genotype-phenotype association between audiometric characteristics and detected genotypes in ARNSHL patients from Serbia. Methods. Ninety-two patients with ARNSHL underwent genetic analysis with PCR-ARMS and sequencing of the GJB2 gene. Audiological analyses were obtained in all patients using a combination of several methods to estimate the degree of hearing loss. Results. Audiological analysis performed in the 92 probands showed moderate to profound range of hearing loss. All identified pathogenic variants accounted for 42.39% of the mutant alleles (78/184 alleles), with the c.35delG mutation being the most frequent (30.43%). Genotype-phenotype correlation in an isolated group of 37 patients bearing c.35delG in the homozygous, compound heterozygous or heterozygous state. In this group the majority of patients (30/37, 81.08%) exhibited severe to profound hearing deficit. Conclusion. Association between genotype and the degree of hearing impairment in patients analyzed in this study demonstrated that patients with bi-allelic truncating mutations i.e. c.35delG, associate with the more severe hearing loss when compared with those identified with only one affected allele. The various degrees of hearing impairment observed in heterozygous patients could be explained by the presence of an undetected second mutation or other modifier genes or environmental causes.

scholarly journals Heterozygous Urinary Abnormality–Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport Syndrome

Kidney360 ◽  
2020 ◽  
Vol 1 (9) ◽  
pp. 936-942
Author(s):  
Tomoko Horinouchi ◽  
Tomohiko Yamamura ◽  
China Nagano ◽  
Nana Sakakibara ◽  
Shinya Ishiko ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Autosomal Recessive ◽  
Clinical Spectrum ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Renal Disorder ◽  
Thin Basement Membrane Disease ◽  
Renal Prognosis ◽  
Urinary Abnormality ◽  
Urinary Abnormalities

BackgroundAutosomal recessive Alport syndrome (ARAS) is an inherited renal disorder caused by homozygous and compound heterozygous mutations in COL4A3 or COL4A4, but the prognostic predictors for this disorder are not yet fully understood. Recently, the magnitude of the clinical spectrum of the COL4A3 and COL4A4 heterozygous state has attracted attention. This spectrum includes asymptomatic carriers of ARAS, benign familial hematuria, thin basement membrane disease, and autosomal dominant Alport syndrome.MethodsWe retrospectively analyzed 49 patients with ARAS from 41 families with a median age of 19 years to examine the clinical features and prognostic factors of ARAS, including the associated genotypes.ResultsThe median age of patients with ARAS at ESKD onset was 27 years. There was no significant association between the presence or absence of hearing loss or truncating mutations and renal prognosis. However, there was a statistically significant correlation between renal prognosis and heterozygous variants that cause urinary abnormalities. Where the urinary abnormality–causing variant was absent or present in only one allele, the median age of ESKD onset was 45 years, whereas the same variant present on both alleles was associated with an age of onset of 15 years (P<0.001).ConclusionsThis study was the first to demonstrate the clinical importance in ARAS of focusing on variants in COL4A3 or COL4A4 that cause urinary abnormalities in both the homozygous or heterozygous state. Although heterozygous mutation carriers of COL4A3 and COL4A4 comprise a broad clinical spectrum, clinical information regarding each variant is important for predicting ARAS prognosis.

Identification of a novel factor X deletion in combination with a missense mutation in the F10 gene

2009 ◽  
Vol 29 (02) ◽  
pp. 184-186 ◽  
Author(s):  
J. Oldenburg ◽  
A. Pavlova ◽  
A. Superti-Furga ◽  
B. Zieger ◽  
I. Hainmann
Keyword(s):  
Missense Mutation ◽  
Young Girl ◽  
Therapeutic Options ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Factor X ◽  
Factor X Deficiency ◽  
Relationship Of ◽  
Compound Heterozygous State

SummaryThe genotype-phenotype relationship of compound heterozygous factor X deficiency in a young girl with severe factor X deficiency and bleeding symptoms is characterized. We identified a novel deletion of exon 6 and a missense mutation (c.856G>A, Val286Met) in exon 7 of the F10 gene leading to a compound heterozygous state and causing severe factor X deficiency. Therapeutic options for patients with symptomatic factor X deficiency are demonstrated.

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