Dataset Information

Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next-generation sequencing.

ABSTRACT:

Background

The extremely high genetic heterogeneity of hearing loss due to diverse group of genes encoding proteins required for development, function, and maintenance of the complex auditory system makes the genetic diagnosis of this disease challenging. Up to now, 121 different genes have been identified for nonsyndromic hearing loss (NSHL), of which 76 genes are responsible for the most common forms of NSHL, autosomal recessive nonsyndromic hearing loss (ARNSHL).

Methods

After excluding mutations in the most common ARNSHL gene, GJB2, by Sanger sequencing, genetic screening for a panel of genes responsible for hereditary hearing impairment performed in 9 individuals with ARNSHL from unrelated Iranian consanguineous pedigrees.

Results

One compound heterozygote and eight homozygote variants, of which five are novel, were identified: CDH23:p.(Glu1970Lys), and p.(Ala1072Asp), GIPC3:p.(Asn82Ser), and (p.Thr41Lys), MYO7A:p.[Phe456Phe]; p.[Met708Val], and p.(Gly163Arg), TECTA:p.(Leu17Leufs*19), OTOF:c.1392+1G>A, and TRIOBP:p.(Arg1068*). Sanger sequencing confirmed the segregation of the variants with the disease in each family.

Conclusion

Finding more variants and expanding the spectrum of hearing impairment mutations can increase the diagnostic value of molecular testing in the screening of patients and can improve counseling to minimize the risk of having affected children for at risk couples.

SUBMITTER: Bitarafan F

PROVIDER: S-EPMC7755797 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next-generation sequencing.

Bitarafan Fatemeh F Seyedena Seyed Yousef SY Mahmoudi Mahdi M Garshasbi Masoud M

Journal of clinical laboratory analysis 20200830 12

<h4>Background</h4>The extremely high genetic heterogeneity of hearing loss due to diverse group of genes encoding proteins required for development, function, and maintenance of the complex auditory system makes the genetic diagnosis of this disease challenging. Up to now, 121 different genes have been identified for nonsyndromic hearing loss (NSHL), of which 76 genes are responsible for the most common forms of NSHL, autosomal recessive nonsyndromic hearing loss (ARNSHL).<h4>Methods</h4>After ...[more]

PMID: 32864763

Similar Datasets

Project description:Hereditary hearing impairment is one of the major and common birth defects in Chinese population. Non-syndromic sensorineural hearing loss (NSHL) is the most common types of hereditary hearing impairment. Genotypically and phenotypically NSHL is extremely heterogenous and follow either autosomal dominant or autosomal recessive or X-linked mode of inheritance. Presently, 127 genes have been identified to be associated with both syndromic and (NSHL). Here, we studied a Chinese family with moderate and profound hearing impairment. The proband is a 30-year old Chinese man. The proband was born with normal hearing and at the age of 5-years, the proband was first noticed with hearing impairment. Gradually and progressively the proband was presented with loss of hearing in his both right and left ears at the age of 30 years. The clinical symptoms, age of onset or progression to loss of hearing was similar in both the proband and his younger brother. The proband's parents are phenotypically normal and non-consanguineous. Clinical diagnosis of the proband and his younger brother has been done by classical pure tone audiogram (PTA). Computed Tomography (CT) found no abnormality in bilateral external ear, middle ear and inner ear. Targeted next generation sequencing was performed with a panel of 127 genes reported to be associated with hereditary hearing impairment. A novel homozygous single nucleotide deletion (c.427delT) in exon 4 of ILDR1 gene has been identified in proband and in his younger brother. Sanger sequencing confirmed that proband's father and mother are carrying this mutation in a heterozygous manner. This mutation has not been identified in 100 normal healthy control individuals. This mutation (c.427delT) causes frameshift (p.Tyr143Ilefs∗19) which leads to the formation of a truncated ILDR1 protein of 162 amino acids instead of the wild type ILDR1 protein of 546 amino acids. ILDR1 associated hereditary hearing impairment is very rare and this is the first report of identifying a loss-of-function mutation in ILDR1 gene associated with hereditary hearing impairment in Chinese population. Our present study also emphasized the significance of rapid, accurate and cost-effective screening for the patient with hereditary hearing impairment by targeted next generation sequencing.

Dataset Information

Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next-generation sequencing.

Background

Methods

Results

Conclusion

Publications

Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next-generation sequencing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets