ABSTRACT
BACKGROUND: Hearing Impairment (HI) can have genetic or environmental causes and in some cases, an interplay of both. Genetic causes are difficult to determine as mutations in more than 90 genes have been shown recently to be responsible for HI. Providing a genetic diagnostic test for HI is therefore a challenge especially for ethnic groups where GJB2 mutations are shown to be rare. RESULTS: Here we show the design and implementation of an amplicon-based targeted sequencing panel that allows the simultaneous sequencing of 87 HI genes. Mutations identified included known pathogenic mutations and novel variants with unknown significance. The diagnostic rate of this panel is 28 % when only pathogenic variants were reported. However, an additional 28 % harbored recurrent combinations of novel or rare single nucleotide variants in the OTOF or PCDH15 genes. Such combinations were not identified in healthy individuals. CONCLUSIONS: Targeted sequencing approach is a very useful strategy for the identification of mutations affecting the HI genes because of its relatively fast turn-around time and cost effectiveness compared to whole-exome sequencing. Further novel or rare variants could be identified by implementing a large-scale screening of HI using our panel which will eventual lead to a higher diagnostic rate.
Subject(s)
Hearing Loss/genetics , High-Throughput Nucleotide Sequencing/methods , Adolescent , Adult , Cadherin Related Proteins , Cadherins/genetics , Case-Control Studies , Child , Child, Preschool , DNA/chemistry , DNA/isolation & purification , DNA/metabolism , Databases, Genetic , Female , Genotype , Hearing Loss/diagnosis , Hearing Loss/pathology , High-Throughput Nucleotide Sequencing/standards , Humans , Male , Membrane Proteins/genetics , Polymorphism, Single Nucleotide , Reproducibility of Results , Saudi Arabia , Young AdultABSTRACT
Nonsyndromic hearing loss (NSHL) affects a substantial proportion of newborns in the world every year. This proportion increases proportionally with the degree of consanguineous marriages in any society. In the Kingdom of Saudi Arabia, consanguineous marriages are common practice and this is associated with a noticeably high frequency of inherited conditions affecting the resulting progeny, including NSHL. Until now there is no published data on the genetic causes of NSHL in Saudi Arabia, which greatly hindered the ability of local genetic counseling and family planning centers to distinguish between hereditary and nonhereditary forms of NSHL and subsequently could not give information on the possible inheritance of deafness. In addition, the lack of validated genetic tests for NSHL delayed the detection of deafness in affected individuals and may have lowered the efficiency of later medical interventions. Further, the population covered in this study is likely to have a multiethnic background caused by decades of religious and economic migration to this region. To address such problems, we undertook the task of unraveling the genetic causes of hearing loss in Saudi Arabia, starting with identifying the GJB2/DFNB1 mutation spectrum in a cohort of unrelated individuals suffering from mild to profound NSHL. A total of 12 reported GJB2 mutations were identified in 17 out of 109 (15.59%) NSHL cases. Biallelic GJB2 mutations were identified in 11 out of the 109 NSHL cases (10.09%), with c.35delG being the most common (7/11, 63.63%). The remaining six patients were found to have monoallelic GJB2 mutations. Interestingly, biallelic GJB2 mutations were not detected in patients of Arab tribal origins, reflecting the genetic heterogeneity of the western area of the Kingdom of Saudi Arabia. Therefore, ethnically targeted genetic screening for GJB2 mutations could be a useful tool toward the management of NSHL in this area.
Subject(s)
Connexins/genetics , Hearing Loss/genetics , Mutation , Amino Acid Substitution , Base Sequence , Codon, Nonsense , Cohort Studies , Connexin 26 , Consanguinity , DNA/genetics , DNA Mutational Analysis , DNA Primers/genetics , Female , Genetic Predisposition to Disease , Humans , Infant, Newborn , Male , Mutation, Missense , Saudi Arabia , Sequence DeletionABSTRACT
OBJECTIVE: To investigate the prevalence of hearing impairment in normal and low birth weight children. METHODS: A survey of 9540 Saudi children below 15 years of age was carried out. The survey was performed in the provinces of the Kingdom of Saudi Arabia from September 1994 to May 1998. The subjects were classified into low birth weight (up to 2.5 kg) and normal birth weight (>2.5 kg) groups. Each child was carefully examined for hearing status. RESULTS: The results of this study showed significantly high prevalence of hearing impairment in low birth weight children (14.87%) as compared to normal birth weight children (9.78%). CONCLUSION: Further studies are warranted to identify the potential risk factors associated with the high prevalence of hearing impairment in low birth weight children.
Subject(s)
Hearing Disorders/epidemiology , Infant, Low Birth Weight , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Prevalence , Residence Characteristics , Risk Factors , Saudi Arabia/epidemiologyABSTRACT
An epidemiological survey was carried out with 9540 children aged up to 12 years to study the prevalence of acute suppurative otitis media and the rate of hearing impairment. A total of 100 (1.05%) were diagnosed with acute otitis media (AOM). The incidence was found to be higher among young children up to 4-years-old and lower in the age group 8-12 years. The male children had slightly higher rate of AOM as compared with female (1.36 and 0.80%), respectively, (P < 0.01). The prevalence of AOM in the children from the different provinces varied, being higher in those from the Southern and Central regions. Also it was found that the prevalence of ASOM was higher among children whose parents were cousins compared with non-relative parents (1.38 and 0.74%) (P > 0.001). Those with poor socio-economic condition showed higher rate especially those living in the Southern part with poor or inadequate health services provided. ASOM was significantly associated with hearing impairment (P < 0.00001).
Subject(s)
Otitis Media/epidemiology , Acute Disease , Adolescent , Child , Child, Preschool , Consanguinity , Diagnostic Techniques, Otological , Female , Humans , Infant , Male , Otitis Media/diagnosis , Saudi Arabia/epidemiologyABSTRACT
OBJECTIVE: To investigate the prevalence of hearing impairment in normal and low birth weight children. METHODS: A survey of 9540 Saudi children below 15 years of age was carried out. The survey was performed in the provinces of the Kingdom of Saudi Arabia from September 1994 to May 1998. The subjects were classified into low birth weight (up to 2.5 kg) and normal birth weight (>2.5 kg) groups. Each child was carefully examined for hearing status. RESULTS: The results of this study showed significantly high prevalence of hearing impairment in low birth weight children (14.87%) as compared to normal birth weight children (9.78%). CONCLUSION: Further studies are warranted to identify the potential risk factors associated with the high prevalence of hearing impairment in low birth weight children.
