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MARVELD2 (DFNB49) mutations in the hearing impaired Central European Roma population--prevalence, clinical impact and the common origin.

Mašindová I, Šoltýsová A, Varga L, Mátyás P, Ficek A, Hučková M, Sůrová M, Šafka-Brožková D, Anwar S, Bene J, Straka S, Janicsek I, Ahmed ZM, Seeman P, Melegh B, Profant M, Klimeš I, Riazuddin S, Kádasi Ľ, Gašperíková D - PLoS ONE (2015)

Bottom Line: Biallelic mutation carriers suffered from prelingual bilateral moderate to profound sensorineural hearing loss.In addition, our results provide support for the hypothesis of a possible common ancestor of the Slovak, Hungarian and Czech Roma as well as Pakistani deaf patients.Testing for the c.1331+2T>C mutation may be recommended in GJB2 negative Roma cases with early-onset sensorineural hearing loss.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Diabetes and Metabolic Disorders & DIABGENE, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.

ABSTRACT

Background: In the present study we aimed: 1) To establish the prevalence and clinical impact of DFNB49 mutations in deaf Roma from 2 Central European countries (Slovakia and Hungary), and 2) to analyze a possible common origin of the c.1331+2T>C mutation among Roma and Pakistani mutation carriers identified in the present and previous studies.

Methods: We sequenced 6 exons of the MARVELD2 gene in a group of 143 unrelated hearing impaired Slovak Roma patients. Simultaneously, we used RFLP to detect the c.1331+2T>C mutation in 85 Hungarian deaf Roma patients, control groups of 702 normal hearing Romanies from both countries and 375 hearing impaired Slovak Caucasians. We analyzed the haplotype using 21 SNPs spanning a 5.34Mb around the mutation c.1331+2T>C.

Results: One pathogenic mutation (c.1331+2T>C) was identified in 12 homozygous hearing impaired Roma patients. Allele frequency of this mutation was higher in Hungarian (10%) than in Slovak (3.85%) Roma patients. The identified common haplotype in Roma patients was defined by 18 SNP markers (3.89 Mb). Fourteen common SNPs were also shared among Pakistani and Roma homozygotes. Biallelic mutation carriers suffered from prelingual bilateral moderate to profound sensorineural hearing loss.

Conclusions: We demonstrate different frequencies of the c.1331+2T>C mutation in hearing impaired Romanies from 3 Central European countries. In addition, our results provide support for the hypothesis of a possible common ancestor of the Slovak, Hungarian and Czech Roma as well as Pakistani deaf patients. Testing for the c.1331+2T>C mutation may be recommended in GJB2 negative Roma cases with early-onset sensorineural hearing loss.

No MeSH data available.


Related in: MedlinePlus

Common ancestral haplotypes of Slovak, Hungarian and Czech Romanies, and Pakistani patients.The haplotypes in Slovak (SK), Czech (CZ), Hungarian (HU) Roma and Pakistani patients with the c.1331+2T>C mutation, and haplotypes in Slovak Roma controls without the c.1331+2T>C mutation. The c.1331+2T>C mutation is shown in bold. The common haplotype is highlighted in light grey.aThe most similar haplotypes found in 5 out of 56 control individuals. In the remaining 51 control individuals, haplotypes were significantly distinguishable.bThe haplotype in Pakistani patients with c.1183-1G>A mutation.
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pone.0124232.g001: Common ancestral haplotypes of Slovak, Hungarian and Czech Romanies, and Pakistani patients.The haplotypes in Slovak (SK), Czech (CZ), Hungarian (HU) Roma and Pakistani patients with the c.1331+2T>C mutation, and haplotypes in Slovak Roma controls without the c.1331+2T>C mutation. The c.1331+2T>C mutation is shown in bold. The common haplotype is highlighted in light grey.aThe most similar haplotypes found in 5 out of 56 control individuals. In the remaining 51 control individuals, haplotypes were significantly distinguishable.bThe haplotype in Pakistani patients with c.1183-1G>A mutation.

Mentions: To confirm the common ancestry of the c.1331+2T>C mutation in all patients from our study, as well as among the Pakistani and Czech subjects where the mutation was first detected, we analyzed 21 SNPs located within approximately 5.34 megabase region around the mutation. The identified common haplotype defined by 18 SNP markers (approx. 3.89 megabases), was shared by all Czech, Slovak and Hungarian Roma patients in a homozygous state, suggesting a common ancestor for this mutation in Central European Roma patients (Fig 1). To determine presence of the identified haplotype in the population sample, a selected subset of SNPs was also genotyped in 56 unrelated Roma individuals without the mutation. The haplotype spanning 18 SNPs was not detected in a homozygous state in any of the analyzed control samples, supporting the hypothesis of a common ancestry of this mutation among these patients. However, in five of control samples (showed in Fig 1), a shorter haplotype in homozygous state was detected. The rest of genotyped control samples did not possess homozygous haplotypes similar to the identified disease haplotype. To further support the existence of the common risk haplotype, the cosegregation of the identified haplotype with the c.1331+2T>C mutation was analyzed within a single family. As shown in the Fig 2, alleles forming the risk haplotypes are present in the affected and carrier individuals.


MARVELD2 (DFNB49) mutations in the hearing impaired Central European Roma population--prevalence, clinical impact and the common origin.

Mašindová I, Šoltýsová A, Varga L, Mátyás P, Ficek A, Hučková M, Sůrová M, Šafka-Brožková D, Anwar S, Bene J, Straka S, Janicsek I, Ahmed ZM, Seeman P, Melegh B, Profant M, Klimeš I, Riazuddin S, Kádasi Ľ, Gašperíková D - PLoS ONE (2015)

Common ancestral haplotypes of Slovak, Hungarian and Czech Romanies, and Pakistani patients.The haplotypes in Slovak (SK), Czech (CZ), Hungarian (HU) Roma and Pakistani patients with the c.1331+2T>C mutation, and haplotypes in Slovak Roma controls without the c.1331+2T>C mutation. The c.1331+2T>C mutation is shown in bold. The common haplotype is highlighted in light grey.aThe most similar haplotypes found in 5 out of 56 control individuals. In the remaining 51 control individuals, haplotypes were significantly distinguishable.bThe haplotype in Pakistani patients with c.1183-1G>A mutation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401708&req=5

pone.0124232.g001: Common ancestral haplotypes of Slovak, Hungarian and Czech Romanies, and Pakistani patients.The haplotypes in Slovak (SK), Czech (CZ), Hungarian (HU) Roma and Pakistani patients with the c.1331+2T>C mutation, and haplotypes in Slovak Roma controls without the c.1331+2T>C mutation. The c.1331+2T>C mutation is shown in bold. The common haplotype is highlighted in light grey.aThe most similar haplotypes found in 5 out of 56 control individuals. In the remaining 51 control individuals, haplotypes were significantly distinguishable.bThe haplotype in Pakistani patients with c.1183-1G>A mutation.
Mentions: To confirm the common ancestry of the c.1331+2T>C mutation in all patients from our study, as well as among the Pakistani and Czech subjects where the mutation was first detected, we analyzed 21 SNPs located within approximately 5.34 megabase region around the mutation. The identified common haplotype defined by 18 SNP markers (approx. 3.89 megabases), was shared by all Czech, Slovak and Hungarian Roma patients in a homozygous state, suggesting a common ancestor for this mutation in Central European Roma patients (Fig 1). To determine presence of the identified haplotype in the population sample, a selected subset of SNPs was also genotyped in 56 unrelated Roma individuals without the mutation. The haplotype spanning 18 SNPs was not detected in a homozygous state in any of the analyzed control samples, supporting the hypothesis of a common ancestry of this mutation among these patients. However, in five of control samples (showed in Fig 1), a shorter haplotype in homozygous state was detected. The rest of genotyped control samples did not possess homozygous haplotypes similar to the identified disease haplotype. To further support the existence of the common risk haplotype, the cosegregation of the identified haplotype with the c.1331+2T>C mutation was analyzed within a single family. As shown in the Fig 2, alleles forming the risk haplotypes are present in the affected and carrier individuals.

Bottom Line: Biallelic mutation carriers suffered from prelingual bilateral moderate to profound sensorineural hearing loss.In addition, our results provide support for the hypothesis of a possible common ancestor of the Slovak, Hungarian and Czech Roma as well as Pakistani deaf patients.Testing for the c.1331+2T>C mutation may be recommended in GJB2 negative Roma cases with early-onset sensorineural hearing loss.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Diabetes and Metabolic Disorders & DIABGENE, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.

ABSTRACT

Background: In the present study we aimed: 1) To establish the prevalence and clinical impact of DFNB49 mutations in deaf Roma from 2 Central European countries (Slovakia and Hungary), and 2) to analyze a possible common origin of the c.1331+2T>C mutation among Roma and Pakistani mutation carriers identified in the present and previous studies.

Methods: We sequenced 6 exons of the MARVELD2 gene in a group of 143 unrelated hearing impaired Slovak Roma patients. Simultaneously, we used RFLP to detect the c.1331+2T>C mutation in 85 Hungarian deaf Roma patients, control groups of 702 normal hearing Romanies from both countries and 375 hearing impaired Slovak Caucasians. We analyzed the haplotype using 21 SNPs spanning a 5.34Mb around the mutation c.1331+2T>C.

Results: One pathogenic mutation (c.1331+2T>C) was identified in 12 homozygous hearing impaired Roma patients. Allele frequency of this mutation was higher in Hungarian (10%) than in Slovak (3.85%) Roma patients. The identified common haplotype in Roma patients was defined by 18 SNP markers (3.89 Mb). Fourteen common SNPs were also shared among Pakistani and Roma homozygotes. Biallelic mutation carriers suffered from prelingual bilateral moderate to profound sensorineural hearing loss.

Conclusions: We demonstrate different frequencies of the c.1331+2T>C mutation in hearing impaired Romanies from 3 Central European countries. In addition, our results provide support for the hypothesis of a possible common ancestor of the Slovak, Hungarian and Czech Roma as well as Pakistani deaf patients. Testing for the c.1331+2T>C mutation may be recommended in GJB2 negative Roma cases with early-onset sensorineural hearing loss.

No MeSH data available.


Related in: MedlinePlus