Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families.

The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes , , , , , , and , with an overall resolve rate of 61.

A novel missense variant in MYO3A is associated with autosomal dominant high-frequency hearing loss in a German family.

Background: MYO3A, encoding the myosin IIIA protein, is associated with autosomal recessive and autosomal dominant nonsyndromic hearing loss. To date, only two missense variants located in the motor-head domain of MYO3A have been described in autosomal dominant families with progressive, mild-to-profound sensorineural hearing loss. These variants alter the ATPase activity of myosin IIIA.

Small fish, big prospects: using zebrafish to unravel the mechanisms of hereditary hearing loss.

Over the past decade, advancements in high-throughput sequencing have greatly enhanced our knowledge of the mutational signatures responsible for hereditary hearing loss. In its present state, the field has a largely uncensored view of protein coding changes in a growing number of genes that have been associated with hereditary hearing loss, and many more that have been proposed as candidate genes. Sequencing data can now be generated using methods that have become widespread and affordable.

Exome-wide copy number variation analysis identifies a COL9A1 in frame deletion that is associated with hearing loss.

Pathogenic variants in COL9A1 are primarily associated with autosomal recessive Stickler syndrome. Patients with COL9A1-associated Stickler syndrome (STL) present hearing loss (HL), ophthalmic manifestations and skeletal abnormalities. However, the clinical spectrum of patients with COL9A1 variants can also include multiple epiphyseal dysplasia, as well as non-syndromic HL that was observed in one previously reported proband.

Phenotypic Characterization of DFNB16-associated Hearing Loss.

Hypothesis: We hypothesized that patients with DFNB16 caused hearing loss show characteristical audiological findings depending on genetic results.

Background: Hearing loss belongs to the most frequent congenital diseases. In 50-70% of individuals, hearing loss is caused by genetic defects.

Hereditary hearing loss SNP-microarray pilot study.

Objectives: Despite recent advancements in diagnostic tools, the genomic landscape of hereditary hearing loss remains largely uncharacterized. One strategy to understand genome-wide aberrations includes the analysis of copy number variation that can be mapped using SNP-microarray technology. A growing collection of literature has begun to uncover the importance of copy number variation in hereditary hearing loss.

The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family.

Background: Genetic heterogeneity and consanguineous marriages make recessive inherited hearing loss in Iran the second most common genetic disorder. Only two reported pathogenic variants (c.323G>C, p.

Confirmation of PDZD7 as a Nonsyndromic Hearing Loss Gene.

Objective: PDZD7 was identified in 2009 in a family with apparent nonsyndromic sensorineural hearing loss. However, subsequent clinical reports have associated PDZD7 with digenic Usher syndrome, the most common cause of deaf-blindness, or as a modifier of retinal disease. No further reports have validated this gene for nonsyndromic hearing loss, intuitively calling correct genotype-phenotype association into question.

A Novel de novo Mutation in CEACAM16 Associated with Postlingual Hearing Impairment.

Mutations in CEACAM16 cause autosomal dominant nonsyndromic hearing loss (DFNA4B). So far, 2 families have been reported with segregating missense mutations, both in the immunoglobulin constant domain A of the CEACAM16 protein. In this study, we used the TruSight One panel to investigate a parent-child trio without familial history of hearing loss and one affected child.

Non-syndromic hearing loss gene identification: A brief history and glimpse into the future.

From the first identified non-syndromic hearing loss gene in 1995, to those discovered in present day, the field of human genetics has witnessed an unparalleled revolution that includes the completion of the Human Genome Project in 2003 to the $1000 genome in 2014. This review highlights the classical and cutting-edge strategies for non-syndromic hearing loss gene identification that have been used throughout the twenty year history with a special emphasis on how the innovative breakthroughs in next generation sequencing technology have forever changed candidate gene approaches. The simplified approach afforded by next generation sequencing technology provides a second chance for the many linked loci in large and well characterized families that have been identified by linkage analysis but have presently failed to identify a causative gene.

Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations.

Purpose: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment.

Methods: Using one of two next-generation sequencing panels containing either 80 or 129 deafness genes, we screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated families) and analyzed 9 normal-hearing controls.