scholarly journals Identification of a Novel COL4A4 Variant in Compound-Heterozygous State in a Patient With Alport Syndrome and Histological Findings Similar to Focal Segmental Glomerulosclerosis (FSGS)

2019 ◽  
Vol 9 ◽  
Author(s):  
Feng Zhu ◽  
Wencheng Li ◽  
Zhenqiong Li ◽  
Hongyan Zhu ◽  
Jing Xiong
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Alport Syndrome ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Histological Findings ◽  
Segmental Glomerulosclerosis ◽  
Compound Heterozygous State

scholarly journals Hydroxypropyl-β-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis

2018 ◽  
Vol 94 (6) ◽  
pp. 1151-1159 ◽  
Author(s):  
Alla Mitrofanova ◽  
Judith Molina ◽  
Javier Varona Santos ◽  
Johanna Guzman ◽  
Ximena A. Morales ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Alport Syndrome ◽  
Segmental Glomerulosclerosis

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.

APOL1 risk genotype in European steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis patients of different African ancestries

2018 ◽  
Vol 34 (11) ◽  
pp. 1885-1893 ◽  
Author(s):  
Olivier Gribouval ◽  
Olivia Boyer ◽  
Bertrand Knebelmann ◽  
Alexandre Karras ◽  
Jacques Dantal ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
West Indies ◽  
African Ancestry ◽  
Compound Heterozygous ◽  
French West Indies ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Segmental Glomerulosclerosis ◽  
Risk Variants

Abstract Background Apolipoprotein L1 (APOL1) risk variants are strongly associated with sporadic focal segmental glomerulosclerosis (FSGS) in populations with African ancestry. We determined the frequency of G1/G2 variants in steroid-resistant nephrotic syndrome (SRNS)/FSGS patients with African or French West Indies ancestry in France and its relationships with other SRNS genes. Methods In a cohort of 152 patients (139 families), the APOL1 risk variants were genotyped by direct Sanger sequencing and pathogenic mutations were screened by next-generation sequencing with a panel including 35 SRNS genes. Results The two risk allele [high-risk (HR)] genotypes were found in 43.1% (66/152) of subjects compared with 18.9% (106/562) in a control population (P < 0.0001): 33 patients homozygous for APOL1 G1 alleles, 4 homozygous for G2 and 29 compound heterozygous for G1 and G2. Compared with patients in the low-risk (LR) group, patients in the HR group were more likely to originate from the French West Indies than from Africa [45/66 (68.2%) versus 30/86 (34.9%); P < 0.0001]. There were more familial cases in the HR group [27 (41.5%) versus 8 (11.4%); P < 0.0001]. However, causative mutations in monogenic SRNS genes were found in only 1 patient in the HR group compared with 16 patients (14 families) in the LR group (P = 0.0006). At diagnosis, patients in the HR group without other mutations were more often adults [35 (53.8%) versus 19 (27.1%); P = 0.003] and had a lower estimated glomerular filtration rate (78.9 versus 98.8 mL/min/1.73 m2; P = 0.02). Conclusions The HR genotype is frequent in FSGS patients with African ancestry in our cohort, especially in those originating from the West Indies, and confer a poor renal prognosis. It is usually not associated with other causative mutations in monogenic SRNS genes.

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 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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