scholarly journals A Common Founder Effect of the Splice Site Variant c.-23+1G>A in GJB2 Gene Causing Autosomal Recessive Deafness 1A (DFNB1A) in Eurasia

2021 ◽  
Author(s):  
Aisen V Solovyev ◽  
Alena Kushniarevich ◽  
Elena Bliznetz ◽  
Marita Bady-Khoo ◽  
Maria R Lalayants ◽  
...  
Keyword(s):  
Splice Site ◽  
Founder Effect ◽  
Autosomal Recessive ◽  
Gjb2 Gene ◽  
Published Data ◽  
Migration Routes ◽  
C 23 ◽  
The World ◽  
Common Founder ◽  
Splice Site Variant

Abstract The mutations in the GJB2 gene are known to be a major cause of autosomal recessive deafness 1A (OMIM 220290). The most common pathogenic variants of the GJB2 gene have high ethno-geographic specificity in their distribution that being attributed to a founder effect related with Neolithic migration routes of Homo sapiens. Curiously, the c.-23+1G>A splice site variant is frequently found among deaf patients of both Caucasian and Asian origin. It is currently unknown whether this mutation did spread across Eurasia as a result of the founder effect or it could have multiple local centers of origin. To determine the origin of the c.-23+1G>A we reconstructed 𝑓2-haplotypes by genotyping SNPs on the Illumina OmniExpress 730K platform in 23 deaf individuals homozygous for this variant from different populations of Eurasia (Yakuts, Tuvinians, Evenk, Kumyk, Armenian, Russians and Slovak). The analysis revealed that the homozygosity regions in different individuals overlapped in one short region with the length of ~5.2 kb. These data support the hypothesis of the common founder effect in distribution of the c.-23+1G>A variant of GJB2 gene. Based on the published data on the c.-23+1G>A prevalence among 16,177 deaf people and calculation of TMRCA of the 𝑓2-haplotypes carrying this variant we reconstructed the potential migration routes of the c.-23+1G>A carriers around the world. This analysis indicates that the c.-23+1G>A variant may have originated approximately 6,000 years ago in the territory of the Caucasus or Middle East, followed by spread throughout Europe, South and Central Asia and other regions of the world.

A common founder effect of the splice site variant c.-23 + 1G > A in GJB2 gene causing autosomal recessive deafness 1A (DFNB1A) in Eurasia

2021 ◽  
Author(s):  
Aisen V. Solovyev ◽  
Alena Kushniarevich ◽  
Elena Bliznetz ◽  
Marita Bady-Khoo ◽  
Maria R. Lalayants ◽  
...  
Keyword(s):  
Splice Site ◽  
Founder Effect ◽  
Autosomal Recessive ◽  
Gjb2 Gene ◽  
C 23 ◽  
Common Founder ◽  
Splice Site Variant

scholarly journals Association of gjb2 gene mutations with non syndromic autosomal recessive deafness in different populations of the world

2014 ◽  
Vol 3 (4) ◽  
pp. 521
Author(s):  
Shahid Hussain ◽  
Mohammad Haroon Khan ◽  
Muhammad Tahir Khan ◽  
Shujah Zeb ◽  
Muhammad Haseeb ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Gene Mutations ◽  
Gjb2 Gene ◽  
The World ◽  
Different Populations

Novel splice-site variant of UCHL1 in an Indian family with autosomal recessive spastic paraplegia-79

2018 ◽  
Vol 63 (8) ◽  
pp. 927-933 ◽  
Author(s):  
Aneek Das Bhowmik ◽  
Siddaramappa J. Patil ◽  
Dipti Vijayrao Deshpande ◽  
Venkatraman Bhat ◽  
Ashwin Dalal
Keyword(s):  
Splice Site ◽  
Autosomal Recessive ◽  
Spastic Paraplegia ◽  
Indian Family ◽  
Splice Site Variant

Genetic testing of two Pakistani patients affected with rare autosomal recessive Fanconi-Bickel syndrome and identification of a novel SLC2A2 splice site variant

2019 ◽  
Vol 32 (11) ◽  
pp. 1229-1233 ◽  
Author(s):  
Hajira Batool ◽  
Bibi Zubaida ◽  
Muhammad Almas Hashmi ◽  
Muhammad Naeem
Keyword(s):  
Splice Site ◽  
Autosomal Recessive ◽  
Complete Blood Count ◽  
Mutation Screening ◽  
Clinical Manifestations ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Glucose Transporter 2 ◽  
The Family ◽  
Splice Site Variant

Abstract Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive carbohydrate metabolism disorder caused by mutations in SLC2A2 encoding the glucose transporter 2 (GLUT2) protein. The clinical manifestations include hepatomegaly, conditional hypo/hyperglycemia, rickets, short stature and proximal renal tubular dysfunction. GLUT2 regulates monosaccharide homeostasis through sugar sensing and transmembrane transportation during high/low glucose levels. In the current study, we present two siblings suffering from FBS. The patients presented with doll-like facies, failure to gain weight and height, abdominal distension and firm hepatomegaly. The family had a history of deaths of twin male siblings in the neonatal period and twin female siblings at ages 10 months and 2.5 years, respectively. Clinical presentation and biochemical investigations including a complete blood count, electrolytes, liver and renal function tests suggested FBS. Mutation screening of SLC2A2 confirmed the diagnosis with identification of a novel homozygous splice site variant predicting an in-frame deletion [p.(Gly166-S169del)] in the GLUT2 protein. The in-silico analysis predicted the variant to affect the three-dimensional conformation of the fourth transmembrane helix of the encoded protein, rendering the non-functionality of GLUT2 in both patients of the family under study.

scholarly journals Genetic analysis of autosomal recessive osteopetrosis in Chuvashiya: the unique splice site mutation in TCIRG1 gene spread by the founder effect

2009 ◽  
Vol 17 (5) ◽  
pp. 664-672 ◽  
Author(s):  
Elena A Bliznetz ◽  
Svetlana M Tverskaya ◽  
Rena A Zinchenko ◽  
Anna V Abrukova ◽  
Ekaterina N Savaskina ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Splice Site ◽  
Founder Effect ◽  
Autosomal Recessive ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Autosomal Recessive Osteopetrosis

scholarly journals High Rates of Three Common GJB2 Mutations c.516G>C, c.-23+1G>A, c.235delC in Deaf Patients from Southern Siberia Are Due to the Founder Effect

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 833 ◽  
Author(s):  
Marina V. Zytsar ◽  
Marita S. Bady-Khoo ◽  
Valeriia Yu. Danilchenko ◽  
Ekaterina A. Maslova ◽  
Nikolay A. Barashkov ◽  
...  
Keyword(s):  
Founder Effect ◽  
Transmembrane Protein ◽  
Indigenous Populations ◽  
Gjb2 Gene ◽  
Southern Siberia ◽  
C 23 ◽  
High Prevalence ◽  
Ethnic History ◽  
Single Marker ◽  
Gjb2 Mutations

The mutations in the GJB2 gene (13q12.11, MIM 121011) encoding transmembrane protein connexin 26 (Cx26) account for a significant portion of hereditary hearing loss worldwide. Earlier we found a high prevalence of recessive GJB2 mutations c.516G>C, c.-23+1G>A, c.235delC in indigenous Turkic-speaking Siberian peoples (Tuvinians and Altaians) from the Tyva Republic and Altai Republic (Southern Siberia, Russia) and proposed the founder effect as a cause for their high rates in these populations. To reconstruct the haplotypes associated with each of these mutations, the genotyping of polymorphic genetic markers both within and flanking the GJB2 gene was performed in 28 unrelated individuals homozygous for c.516G>C (n = 18), c.-23+1G>A (n = 6), or c.235delC (n = 4) as well as in the ethnically matched controls (62 Tuvinians and 55 Altaians) without these mutations. The common haplotypes specific for mutations c.516G>C, c.-23+1G>A, or c.235delC were revealed implying a single origin of each of these mutations. The age of mutations estimated by the DMLE+ v2.3 software and the single marker method is discussed in relation to ethnic history of Tuvinians and Altaians. The data obtained in this study support a crucial role of the founder effect in the high prevalence of GJB2 mutations c.516G>C, c.-23+1G>A, c.235delC in indigenous populations of Southern Siberia.

scholarly journals Founder Effect of a c.828+3A>T Splice Site Mutation in Peripherin 2 (PRPH2) Causing Autosomal Dominant Retinal Dystrophies

2015 ◽  
Vol 133 (5) ◽  
pp. 511 ◽  
Author(s):  
Suma P. Shankar ◽  
David G. Birch ◽  
Richard S. Ruiz ◽  
Dianna K. Hughbanks-Wheaton ◽  
Lori S. Sullivan ◽  
...  
Keyword(s):  
Splice Site ◽  
Founder Effect ◽  
Autosomal Dominant ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Retinal Dystrophies

scholarly journals A rare large duplication of MLH1 identified in Lynch syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abhishek Kumar ◽  
Nagarajan Paramasivam ◽  
Obul Reddy Bandapalli ◽  
Matthias Schlesner ◽  
Tianhui Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Lynch Syndrome ◽  
Splice Site ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Splice Donor Site ◽  
Laboratory Diagnostics ◽  
Mmr Genes ◽  
Base Pair Deletion ◽  
Splice Site Variant

Abstract Background The most frequently identified strong cancer predisposition mutations for colorectal cancer (CRC) are those in the mismatch repair (MMR) genes in Lynch syndrome. Laboratory diagnostics include testing tumors for immunohistochemical staining (IHC) of the Lynch syndrome-associated DNA MMR proteins and/or for microsatellite instability (MSI) followed by sequencing or other techniques, such as denaturing high performance liquid chromatography (DHPLC), to identify the mutation. Methods In an ongoing project focusing on finding Mendelian cancer syndromes we applied whole-exome/whole-genome sequencing (WES/WGS) to 19 CRC families. Results Three families were identified with a pathogenic/likely pathogenic germline variant in a MMR gene that had previously tested negative in DHPLC gene variant screening. All families had a history of CRC in several family members across multiple generations. Tumor analysis showed loss of the MMR protein IHC staining corresponding to the mutated genes, as well as MSI. In family A, a structural variant, a duplication of exons 4 to 13, was identified in MLH1. The duplication was predicted to lead to a frameshift at amino acid 520 and a premature stop codon at amino acid 539. In family B, a 1 base pair deletion was found in MLH1, resulting in a frameshift and a stop codon at amino acid 491. In family C, we identified a splice site variant in MSH2, which was predicted to lead loss of a splice donor site. Conclusions We identified altogether three pathogenic/likely pathogenic variants in the MMR genes in three of the 19 sequenced families. The MLH1 variants, a duplication of exons 4 to 13 and a frameshift variant, were novel, based on the InSiGHT and ClinVar databases; the MSH2 splice site variant was reported by a single submitter in ClinVar. As a variant class, duplications have rarely been reported in the MMR gene literature, particularly those covering several exons.

scholarly journals Systematic Review of Hepatitis E Virus in Brazil: A One-Health Approach of the Human-Animal-Environment Triad

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2290
Author(s):  
Danny Franciele da Silva Dias Moraes ◽  
João R. Mesquita ◽  
Valéria Dutra ◽  
Maria São José Nascimento
Keyword(s):  
Systematic Review ◽  
One Health ◽  
Hepatitis E ◽  
Published Data ◽  
Surveillance Systems ◽  
Industrialized Countries ◽  
Genotype 3 ◽  
The World ◽  
Waterborne Transmission ◽  
Sanitary Conditions

Brazil is the fifth largest country in the world with diverse socioeconomic and sanitary conditions, also being the fourth largest pig producer in the world. The aim of the present systematic review was to collect and summarize all HEV published data from Brazil (from 1995 to October 2020) performed in humans, animals, and the environment, in a One Health perspective. A total of 2173 papers were retrieved from five search databases (LILACs, Mendeley, PubMed, Scopus, and Web of Science) resulting in 71 eligible papers after application of exclusion/inclusion criteria. Data shows that HEV genotype 3 (HEV-3) was the only retrieved genotype in humans, animals, and environment in Brazil. The South region showed the highest human seroprevalence and also the highest pig density and industry, suggesting a zoonotic link. HEV-1 and 2 were not detected in Brazil, despite the low sanitary conditions of some regions. From the present review we infer that HEV epidemiology in Brazil is similar to that of industrialized countries (only HEV-3, swine reservoirs, no waterborne transmission, no association with low sanitary conditions). Hence, we alert for the implementation of HEV surveillance systems in swine and for the consideration of HEV in the diagnostic routine of acute and chronic hepatitis in humans.

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