Genetic linkage analysis of 15 DFNB loci in a group of Iranian families with autosomal recessive hearing loss

Hearing loss [HL] is the most frequent sensory birth defect in humans. Autosomal recessive non-syndromic HL [ARNSHL] is the most common type of hereditary HL. It is extremely heterogeneous and over 70 loci [known as DFNB] have been identified. This study was launched to determine the relative contribution of more frequent loci in a cohort of ARNSHL families. Thirty-seven Iranian families including 36 ARNSHL families and 1 family with Pendred syndrome each with >/= 4 affected individuals, from seven provinces of Iran, were ascertained. DFNB1 contribution was initially studied by DNA sequencing of GJB2 and linkage analysis using the relative STR markers. The excluded families were then subjected to homozygosity mapping for fifteen ARNSHL loci. Sixteen families were found to be linked to seven different known loci, including DFNB1 [6 families], DFNB4 [3 families +1 family with Pendred syndrome], DFNB63 [2 families], DFNB2 [1 family], DFNB7/11 [1 family], DFNB9 [1 family] and DFNB21 [1 family]. DNA sequencing of the corresponding genes is in progress to identify the pathogenic mutations. The genetic causes were clarified in 43.2% of the studied families, giving an overview of the causes of ARNSHL in Iran. DFNB4 is ranked second after DFNB1 in the studied cohort. More genetic and epigenetic investigations will have to be done to reveal the causes in the remaining families

[Prevalence of constitutive and inducible resistance to clindamycin in staphylococci isolates from Hajar and Kashani hospitals in Shahrekord, 2008]

Resistance to clindamycin [CL] in Staphylococcus aureus is both constitutive and inducible. In the present study, the prevalence of the constitutive and inducible resistance to CL was investigated by disk diffusion and double-disk diffusion [D-test] methods. This descriptive-analytical study was performed on 230 Staphylococcus isolates. D-test was carried out for all the isolates with resistant phenotype for erythromycin and susceptible phenotype for CL. 15 micro g erythromycin and 2 micro g CL disks were placed on plate at a distance of 15 mm. The appearance of D-shaped zones around the strains was checked after proper incubation. Of the 230 staphylococcus isolates, 55.6% were susceptible to CL, 37.5% had constitutive and 5.2% had inducible resistance to CL. The frequencies of constitutive and inducible resistance for CL in methicillin-resistant Staphylococcus aureus [MRSA] isolates were 66% and 9%, respectively and the frequencies of constitutive and inducible resistance for CL in methicillin-susceptible isolates [MSSA] were 15.4% and 2.3%, respectively. Statistical tests revealed the inducible resistance in MRS isolates to be 4.2 times more frequent than that in MSS isolates. The inducible resistance frequency was 10.8- fold in MRSA compared to MSSA isolates. The study results showed that the inducible resistance should be determined by D-test in all methicillin-resistant staphylococcus isolates and also staphylococcus strains resistant to erythromycin and susceptible to CL

[Mutation screening of GJB2 and GJB6 and genetic linkage study of three prevalent DFNB loci in Iranian families with autosomal recessive non-syndromic hearing loss]

The incidence of prelingual hearing loss [HL] is about 1 in 1000 neonates of which, more than 60% of cases are inherited. Non-syndromic HL [NSHL] is extremely heterogeneous: more than 100 loci have been identified. The most common form of NSHL is the autosomal recessive form [ARNSHL]. Here, we have investigated CX26 [GJB2] and CX30 [GJB6] gene mutation and linkage analysis of 3 known loci in Iranian families. A cohort of 36 big ARNSHL pedigrees from 7 provinces of Iran was investigated. All of the families were examined for the presence of GJB2 and GJB6 [del D13S1830 and del D13S1854] mutations using direct sequencing and multiplex PCR, respectively. The negative mutations pedigrees for the above-mentioned mutations, were then tested for the linkage to the 3 known loci, including DFNB3[MYO7A], DFNB4[SLC26A4] and DFNB7/11[TMC1], using STR markers and conventional PCR and PAGE. Six families had GJB2 mutations. No GJB6 mutation was found. Totally, 3 families showed linkage to DFNB4 and 1 family was linked to DFNB7/11. DFNB1 [GJB2] and DFNB4 are the main causes of ARNSHL in our study samples and GJB6 mutations are apparently absent in the Iranian population