A novel recessive PDZD7 bi-allelic mutation in an Iranian family with non-syndromic hearing loss

Abstract Background Autosomal recessive non-syndromic hearing loss (ARNSHL) is genetically and phenotypically heterogeneous with over 110 genes causally implicated in syndromic and non-syndromic hearing loss. Here, we investigate the genetic etiology of deafness in two GJB2 and GJB6 negative patients presenting with pre-lingual, progressive, severe hearing loss. Methods Targeted exome sequencing (TES) using Next Generation Illumina Sequencing was used to analyze the exonic and some other important genomic regions of 154 genes in the proband. Subsequently, the mutation found was confirmed by Sanger sequencing in other affected sibling and healthy family members. The possible impact of the reported mutation on the corresponding protein was also evaluated by using bioinformatics tools. Moreover, the affected patients underwent audiological and ophthalmic evaluations. Results TES identified a novel homozygous missense mutation c.251T>C (p.I84T) in exon 3 of PDZD7 gene. In addition, segregation and phenotype-genotype correlation analysis as well as in-silico evaluations confirmed the autosomal recessive inheritance pattern and disease-causing nature of mutation found. Conclusions In overall, our finding could expand the pathogenic mutations spectrum and strengthens the clinical importance of the PDZD7 gene in ARNSHL patients. It can also aid to conduct genetic counseling, prenatal diagnosis and clinical management of these types of genetic disorders.

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A Novel Recessive PDZD7 Bi-Allelic Mutation in an Iranian Family with Non-Syndromic Hearing Loss

10.21203/rs.3.rs-136141/v1 ◽

2020 ◽

Author(s):

Hossein Fahimi ◽

Samira Behroozi ◽

Sadaf Noavar ◽

Farshid Parvini

Keyword(s):

Hearing Loss ◽

Genetic Disorders ◽

Clinical Importance ◽

Autosomal Recessive Inheritance ◽

Affected Sibling ◽

Healthy Family ◽

Syndromic Hearing Loss ◽

Genomic Regions ◽

Allelic Mutation ◽

Genotype Correlation

Abstract BackgroundAutosomal recessive non-syndromic hearing loss (ARNSHL) is genetically and phenotypically heterogeneous with over 110 genes causally implicated in syndromic and non-syndromic hearing loss (HL). Here, we investigate the genetic etiology of deafness in twoGJB2 and GJB6 negative patients presenting with pre-lingual, progressive, severe hearing loss.MethodsTargeted exome sequencing (TES) using Next Generation Illumina Sequencing was used to analyze the exonic and some other important genomic regions of 154 genes in the proband. Subsequently, the mutation found was confirmed by Sanger sequencing in other affected sibling and healthy family members. The possible impact of the reported mutation on the corresponding protein was also evaluated by using bioinformatics tools. Moreover, the affected patients underwent audiological and ophthalmic evaluations.ResultsTES identified a novel homozygous missense mutation c.251T>C (p.I84T) in exon 3 of PDZD7 gene. In addition, segregation and phenotype-genotype correlation analysis as well as in-silico evaluations confirmed the autosomal recessive inheritance pattern and disease-causing nature of mutation found. ConclusionsIn overall, our finding could expand the pathogenic mutations spectrum and strengthens the clinical importance of the PDZD7 gene in ARNSHL patients. It can also aid to conduct genetic counseling, prenatal diagnosis and clinical management of these types of genetic disorders.

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Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

10.21203/rs.3.rs-132767/v1 ◽

2020 ◽

Author(s):

Pengfei Liang ◽

Fengping Chen ◽

Shujuan Wang ◽

Qiong Li ◽

Wei Li ◽

...

Keyword(s):

Hearing Loss ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Large Scale ◽

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Chinese Families ◽

Whole Exome ◽

Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

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Whole Exome Sequencing of Six Chinese Families with Hereditary Non-syndromic Hearing Loss

10.21203/rs.3.rs-294215/v1 ◽

2021 ◽

Author(s):

Pengfei Liang ◽

Fengping Chen ◽

Shujuan Wang ◽

Qiong Li ◽

Wei Li ◽

...

Keyword(s):

Hearing Loss ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Large Scale ◽

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Chinese Families ◽

Whole Exome ◽

Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results:Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions:Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

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High prevalence of theW24X mutation in the gene encoding connexin-26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.30884 ◽

2005 ◽

Vol 137A (3) ◽

pp. 255-258 ◽

Cited By ~ 52

Author(s):

Araceli Álvarez ◽

Ignacio del Castillo ◽

Manuela Villamar ◽

Luis A. Aguirre ◽

Anna González-Neira ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Connexin 26 ◽

Gene Encoding ◽

High Prevalence ◽

Syndromic Hearing Loss

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Genetic hearing loss: a study of 228 Brazilian patients

Genetics and Molecular Biology ◽

10.1590/s1415-47572000000100004 ◽

2000 ◽

Vol 23 (1) ◽

pp. 25-27 ◽

Cited By ~ 3

Author(s):

Silvia Bragagnolo Longhitano ◽

Décio Brunoni

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Autosomal Dominant ◽

Autosomal Recessive Inheritance ◽

Recessive Inheritance ◽

Dominant Inheritance ◽

Genetic Etiology ◽

Parental Consanguinity ◽

Genetic Hearing Loss ◽

Associated Abnormalities

We studied 228 patients, with suspected or confirmed genetic hearing loss, in order to determine the clinical and genetic diagnoses and etiology of each case. Deafness with no associated abnormalities was found in 146 patients (64%) belonging to 112 families. Syndromic deafness was diagnosed in 82 patients (36%) belonging to 76 families. The genetic etiology was as follows: autosomal recessive inheritance in 40.8% of syndromics and non-syndromics, autosomal dominant inheritance in 13.2% and X-linked recessive in 1.3%. In 44.7% of the cases, the etiology of the hearing loss could not be determined. Monogenic causes are the most possible etiology in the latter cases. Parental consanguinity was found in 22.4% of the cases, and deafness was bilateral, profound and neurosensorial in 47.4% of the patients. An early onset of hearing loss (< 2 years of age) occurred in 46.5% of the cases. These results are similar to previous literature reports.

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