Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran
Background: We aimed to determine the contribution of four DFNB loci and mutation analysis of gap junction beta-2 (GJB2) and GJB4 genes in autosomal recessive nonsyndromic hearing loss (ARNSHL) in South of Iran. Materials and Methods: A total of 36 large ARNSHL pedigrees with at least two affected s...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2017-01-01
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| Series: | Journal of Research in Medical Sciences |
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| Online Access: | http://www.jmsjournal.net/article.asp?issn=1735-1995;year=2017;volume=22;issue=1;spage=99;epage=99;aulast=Laleh |
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| author | Masoud Akbarzadeh Laleh Marzieh Naseri Ali Akbar Poursadegh Zonouzi Ahmad Poursadegh Zonouzi Marjan Masoudi Najmeh Ahangari Leila Shams Azim Nejatizadeh |
| author_facet | Masoud Akbarzadeh Laleh Marzieh Naseri Ali Akbar Poursadegh Zonouzi Ahmad Poursadegh Zonouzi Marjan Masoudi Najmeh Ahangari Leila Shams Azim Nejatizadeh |
| author_sort | Masoud Akbarzadeh Laleh |
| collection | DOAJ |
| description | Background: We aimed to determine the contribution of four DFNB loci and mutation analysis of gap junction beta-2 (GJB2) and GJB4 genes in autosomal recessive nonsyndromic hearing loss (ARNSHL) in South of Iran. Materials and Methods: A total of 36 large ARNSHL pedigrees with at least two affected subjects were enrolled in the current study. The GJB2 and GJB4 genes mutations were screened using direct sequencing method. The GJB2 and GJB4 negative families were analyzed for the linkage to DFNB21, DFNB24, DFNB29, and DFNB42 loci by genotyping the corresponding STR markers using polymerase chain reaction-PAGE method. Results: We found a homozygous nonsense mutation W77X and a homozygous missense mutation C169W in 5.55% of studied families in GJB2 and GJB4 genes, respectively. Five heterozygous mutations including V63G, A78T, and R127H in GJB2 gene, and R103C and R227W in GJB4 gene were detected. We identified two novel variations V63G in GJB2 and R227W in GJB4. In silico analysis predicted that both novel variations are deleterious mutations. We did not unveil any linkage between DFNB21, DFNB24, DFNB29, and DFNB42 loci and ARNSHL among studied families. Conclusion: This is the first report of GJB2 and GJB4 mutations from Hormozgan population. According to the previous publications regarding GJB2 and GJB4 mutations, the distribution of the mutations is different from other parts of Iran that should be considered in primary health-care programs. Further investigations are needed to evaluate the contribution of other loci in ARNSHL subjects in South of Iran. |
| first_indexed | 2024-04-12T07:01:37Z |
| format | Article |
| id | doaj.art-2a9c924d1103438aaa6dda6deb30df95 |
| institution | Directory Open Access Journal |
| issn | 1735-1995 1735-7136 |
| language | English |
| last_indexed | 2024-04-12T07:01:37Z |
| publishDate | 2017-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Journal of Research in Medical Sciences |
| spelling | doaj.art-2a9c924d1103438aaa6dda6deb30df952022-12-22T03:43:00ZengWolters Kluwer Medknow PublicationsJournal of Research in Medical Sciences1735-19951735-71362017-01-01221999910.4103/jrms.JRMS_976_16Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, IranMasoud Akbarzadeh LalehMarzieh NaseriAli Akbar Poursadegh ZonouziAhmad Poursadegh ZonouziMarjan MasoudiNajmeh AhangariLeila ShamsAzim NejatizadehBackground: We aimed to determine the contribution of four DFNB loci and mutation analysis of gap junction beta-2 (GJB2) and GJB4 genes in autosomal recessive nonsyndromic hearing loss (ARNSHL) in South of Iran. Materials and Methods: A total of 36 large ARNSHL pedigrees with at least two affected subjects were enrolled in the current study. The GJB2 and GJB4 genes mutations were screened using direct sequencing method. The GJB2 and GJB4 negative families were analyzed for the linkage to DFNB21, DFNB24, DFNB29, and DFNB42 loci by genotyping the corresponding STR markers using polymerase chain reaction-PAGE method. Results: We found a homozygous nonsense mutation W77X and a homozygous missense mutation C169W in 5.55% of studied families in GJB2 and GJB4 genes, respectively. Five heterozygous mutations including V63G, A78T, and R127H in GJB2 gene, and R103C and R227W in GJB4 gene were detected. We identified two novel variations V63G in GJB2 and R227W in GJB4. In silico analysis predicted that both novel variations are deleterious mutations. We did not unveil any linkage between DFNB21, DFNB24, DFNB29, and DFNB42 loci and ARNSHL among studied families. Conclusion: This is the first report of GJB2 and GJB4 mutations from Hormozgan population. According to the previous publications regarding GJB2 and GJB4 mutations, the distribution of the mutations is different from other parts of Iran that should be considered in primary health-care programs. Further investigations are needed to evaluate the contribution of other loci in ARNSHL subjects in South of Iran.http://www.jmsjournal.net/article.asp?issn=1735-1995;year=2017;volume=22;issue=1;spage=99;epage=99;aulast=LalehConnexin 30.3deafnessgap junction beta-2linkage analysis |
| spellingShingle | Masoud Akbarzadeh Laleh Marzieh Naseri Ali Akbar Poursadegh Zonouzi Ahmad Poursadegh Zonouzi Marjan Masoudi Najmeh Ahangari Leila Shams Azim Nejatizadeh Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran Journal of Research in Medical Sciences Connexin 30.3 deafness gap junction beta-2 linkage analysis |
| title | Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran |
| title_full | Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran |
| title_fullStr | Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran |
| title_full_unstemmed | Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran |
| title_short | Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran |
| title_sort | diverse pattern of gap junction beta 2 and gap junction beta 4 genes mutations and lack of contribution of dfnb21 dfnb24 dfnb29 and dfnb42 loci in autosomal recessive nonsyndromic hearing loss patients in hormozgan iran |
| topic | Connexin 30.3 deafness gap junction beta-2 linkage analysis |
| url | http://www.jmsjournal.net/article.asp?issn=1735-1995;year=2017;volume=22;issue=1;spage=99;epage=99;aulast=Laleh |
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