46 research outputs found
Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease
Meniere’s disease (MD) is a clinical spectrum of rare disorders characterized by vertigo
attacks, associated with sensorineural hearing loss (SNHL) and tinnitus involving low to
medium frequencies. Although it shows familial aggregation with incomplete phenotypic
forms and variable expressivity, most cases are considered sporadic. The aim of this
study was to investigate the burden for rare variation in SNHL genes in patients with
sporadic MD. We conducted a targeted-sequencing study including SNHL and familial
MD genes in 890 MD patients to compare the frequency of rare variants in cases using
three independent public datasets as controls. Patients with sporadic MD showed a
significant enrichment of missense variants in SNHL genes that was not found in the
controls. The list of genes includes GJB2, USH1G, SLC26A4, ESRRB, and CLDN14. A
rare synonymous variant with unknown significance was found in the MARVELD2 gene
in several unrelated patients with MD. There is a burden of rare variation in certain SNHL
genes in sporadicMD. Furthermore, the interaction of common and rare variants in SNHL
genes may have an additive effect on MD phenotype. This study will contribute to design
a gene panel for the genetic diagnosis of MD.This study was funded by FPS-PI0496-2014 and EF-0247-
2017 from Consejeria de Salud, Spain, 2016-MeniereSociety
Grant, UK and Luxembourg National Research Fund
(INTER/Mobility/17/11772209)
Identification of MYO6 copy number variation associated with cochlear aplasia by targeted sequencing
Heterogeneity of hereditary hearing loss in Iran: A comprehensive review
A significant contribution to the causes of hereditary hearing impairment comes from genetic factors. More than 120 genes and 160 loci have been identified to be involved in hearing impairment. Given that consanguine populations are more vulnerable to most inherited diseases, such as hereditary hearing loss (HHL), the genetic picture of HHL among the Iranian population, which consists of at least eight eth¬nic subgroups with a high rate of intermarriage, is expected to be highly heterogeneous. Using an electronic literature review through vari¬ous databases such as PubMed, MEDLINE, and Scopus, we review the current picture of HHL in Iran. In this review, we present more than 39 deafness genes reported to cause non-syndromic HHL in Iran, of which the most prevalent causative genes include GJB2, SLC26A4, MYO15A, and MYO7A. In addition, we highlight some of the more common genetic causes of syndromic HHL in Iran. These results are of importance for further investigation and elucidation of the molecular basis of HHL in Iran and also for developing a national diagnostic tool tailored to the Iranian context enabling early and efficient diagnosis ofhereditary hearing impairment. © 2016, Academy of Medical Sciences of I.R. Iran. All rights reserved