title: First report of prevalence c.IVS1+1G>A and del (GJB6-13S1854) mutations in Syrian families with non-syndromic sensorineural hearing loss.
abstract: OBJECTIVE
  Mutations in GJB2 and GJB6 genes are a frequent cause of congenital non-syndromic hearing loss (NSHL). Mutational screening has usually focused on coding region of GJB2 gene. A few studies have been conducted on the non-coding region and exon 1. c.IVS1+1G>A (a splice site mutation in GJB2 gene have been detected as disruptive mutation. Del (GJB6 D13S1830) is found in many populations, but del (GJB6 D13S1854) is reported from a few restricted countries. This study was carried out to investigate the prevalence of splice site mutation c.IVS1+1G>A and two common deletions in GJB6 gene as the genetic etiology of hearing impairment in 70 Syrian families.
  
  
  METHODS
  The frequency of the c.IVS1+1G>A mutation and two deletions were determined by PCR-RFLP and A multiplex PCR assay.
  
  
  RESULTS
  Our results showed a high prevalence of IVS1+1G>A mutation (20%) and del(GJB6-D13S1854) (15.7%) in deaf families. The homozygous genotype (c.IVS1+1G>A/c.IVS1+1G>A) was observed in one family and the compound heterozygous genotypes (c.35delG/c.IVS1+1G>A) and (c.IVS1+1G>A/V153I) were observed in 7 families and one family respectively. Also, the heterozygous state (c.IVS1+1G>A/unknown) was detected in 5 families. The study of del((GJB6-D13S1854) was showed a compound heterozygous genotype del((GJB6-D13S1854)/c.IVS1+1G>A) in the same families (5 families) having heterozygous genotype of c.IVS1+1G>A mutation. Also, del(GJB6-D13S1854) is combined with c.35delG mutation in 2 families and it was observed in the heterozygous state del(GJB6-D13S1854)/unknown) in 4 families. In contrast, the del(GJB6-D13S1830) described in many population was absent in our patients.
  
  
  CONCLUSIONS
  Our findings indicate to significant contribution of the splice site mutation and del(GJB6-D13S1854) in our deaf families and these mutations were important causes of hearing impairment.
authors.affiliation: Human Genetics Division, Molecular Biology and Biotechnology Department, Atomic Energy Commission, Damascus, Syria. Electronic address: ascientific14@aec.org.sy.
authors.forename: Walid
authors.initials: W
authors.lastname: Al-Achkar
authors.affiliation: Human Genetics Division, Molecular Biology and Biotechnology Department, Atomic Energy Commission, Damascus, Syria.
authors.forename: Bassel
authors.initials: B
authors.lastname: Al-Halabi
authors.affiliation: Human Genetics Division, Molecular Biology and Biotechnology Department, Atomic Energy Commission, Damascus, Syria.
authors.forename: Bashar
authors.initials: B
authors.lastname: Ali
authors.affiliation: Human Genetics Division, Molecular Biology and Biotechnology Department, Atomic Energy Commission, Damascus, Syria.
authors.forename: Faten
authors.initials: F
authors.lastname: Moassass
mesh_terms: D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D005091:Exons; D005260:Female; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017384:Sequence Deletion; D013593:Syria
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26
keywords: GJB2; GJB6; IVS1+1G>A; Non- syndromic hearing loss (NSHL); Syrian