title: Update of the GJB2/DFNB1 mutation spectrum in Russia: a founder Ingush mutation del(GJB2-D13S175) is the most frequent among other large deletions.
abstract: Although mutations in the GJB2 gene sequence make up the majority of variants causing autosomal-recessive non-syndromic hearing loss, few large deletions have been shown to contribute to DFNB1 deafness. Currently, genetic testing for DFNB1 hearing loss includes GJB2 sequencing and DFNB1 deletion analysis for two common large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854). Here, we report frequency in Russia, clinical significance and evolutionary origins of a 101 kb deletion, del(GJB2-D13S175), recently identified by us. In multiethnic cohort of 1104 unrelated hearing loss patients with biallelic mutations at the DFNB1 locus, the del(GJB2-D13S175) allele frequency of up to 0.5% (11/2208) was determined and this allele was shown to be predominantly associated with profound sensorineural hearing loss. Additionally, eight previously unpublished GJB2 mutations were described in this study. All patients carrying del(GJB2-D13S175) were of the Ingush ancestry. Among normal hearing individuals, del(GJB2-D13S175) was observed in Russian Republic of Ingushetia with a carrier rate of ~1% (2/241). Analysis of haplotypes associated with the deletion revealed a common founder in the Ingushes, with age of the deletion being ~3000 years old. Since del(GJB2-D13S175) was missed by standard methods of GJB2 analysis, del(GJB2-D13S175) detection has been added to our routine testing strategy for DFNB1 hearing loss.
authors.affiliation: The Federal Agency for Scientific Organizations, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moscow, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Bliznetz
authors.affiliation: Federal Medical and Biological Agency, Federal State-Funded Institution of Science, National Research Center for Audiology and Hearing Rehabilitation, Moscow, Russia.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Lalayants
authors.affiliation: Federal Medical and Biological Agency, Federal State-Funded Institution of Science, National Research Center for Audiology and Hearing Rehabilitation, Moscow, Russia.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Markova
authors.affiliation: The Federal Agency for Scientific Organizations, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moscow, Russia.|The Russian Academy of Sciences, Federal State-Funded Institution of Science, Vavilov Institute of General Genetics, Moscow, Russia.
authors.forename: Oleg P
authors.initials: OP
authors.lastname: Balanovsky
authors.affiliation: The Federal Agency for Scientific Organizations, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moscow, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Balanovska
authors.affiliation: The Federal Agency for Scientific Organizations, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moscow, Russia.|The Russian Academy of Sciences, Federal State-Funded Institution of Science, Vavilov Institute of General Genetics, Moscow, Russia.
authors.forename: Roza A
authors.initials: RA
authors.lastname: Skhalyakho
authors.affiliation: The Ministry of Health, Federal State-Funded Educational Institution of Higher Education, Kuban State Medical University, Krasnodar, Russia.
authors.forename: Elvira A
authors.initials: EA
authors.lastname: Pocheshkhova
authors.affiliation: The Ministry of Health, State Budgetary Healthcare Institution, Clinical-Diagnostic Center of Mother and Child Health Protection, Yekaterinburg, Russia.
authors.forename: Natalya V
authors.initials: NV
authors.lastname: Nikitina
authors.affiliation: State Autonomous Healthcare Institution, Regional Clinical Center of Specialized Medical Care, Vladivostok, Russia.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Voronin
authors.affiliation: The Ministry of Health, State Budgetary Healthcare Institution, Leningrad Regional Clinical Hospital, Saint Petersburg, Russia.
authors.forename: Elena K
authors.initials: EK
authors.lastname: Kudryashova
authors.affiliation: Federal State Budgetary Educational Institution of Higher Education, Saint Petersburg University, Saint Petersburg, Russia.
authors.forename: Oleg S
authors.initials: OS
authors.lastname: Glotov
authors.affiliation: The Federal Agency for Scientific Organizations, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moscow, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Polyakov
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D012426:Russia / Q000453:epidemiology; D017384:Sequence Deletion
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26