Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort

Purpose:Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).Methods:After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.Results:We detected ARNSD-causing variants in 90 (56) families, 54 of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13), MYO7A (11), SLC26A4 (10), TMPRSS3 (9), TMC1 (8), ILDR1 (6), and CDH23 (4). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.Conclusion:We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56 of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371. © American College of Medical Genetics and Genomics

Screening of OTOF mutations in Iran: A novel mutation and review

Objective: Mutations in OTOF have been reported to cause nonsyndromic hearing loss in different populations. The purpose of this study is screening of OTOF mutations in Iranian population. Methods: Thirty-eight consanguineous families affected with autosomal recessive nonsyndromic hearing loss (ARNSHL) and negative for GJB2 or GJB6 mutations were screened by autozygosity mapping and Sanger sequencing to find OTOF mutations. Results: A novel homozygous frameshift mutation (c.1981dupG) was found to cause hearing loss in one family and no other OTOF variants were detected in the remaining families. The affected individuals were homozygous forp. D661GfsX2 causing defect in long isoform of otoferlin. Conclusions: We conclude that OTOF mutations are not the major cause of ARNSHL in the Iranian population but still may play an important role in HL; therefore evaluation the OTOF gene is of concern. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Impact of Consanguineous Marriages in GJB2-Related Hearing Loss in the Iranian Population: A Report of a Novel Variant

Mutations in GJB2 and GJB6 genes are the main causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) in many populations. Here, we investigated GJB2 and GJB6 mutations in 114 patients from 77 affected ARNSHL families including 54 consanguineous marriages and 23 nonrelative marriages in the Iranian population. Clinical studies and genetic counseling were performed for all families. GJB2 and GJB6 genes were directly sequenced. Three known GJB6 large deletions del(GJB6-D13S1830), del(GJB6-D13S1854), and a 920 kb deletion were also checked by quantification of a common deleted region within the GJB6 gene. The frequency of consanguinity was 70.13% among the studied families. Biallelic GJB2 mutations were 16.67% in consanguineous marriages and 4.35% in nonrelative marriages. Mutations found were 35delG, delE120, R127H, M163V, W24X, V37I, G12D, V84A, 313-326del14, and E110K. The latter was a novel variant. Neither point mutation nor a large deletion in the GJB6 gene was found in the population. Mean frequency of GJB2 mutations was 17.92%. GJB2 mutations (and not GJB6 mutations) are the major causes of hearing loss in Iran. The role of consanguineous marriages is also highlighted in occurrence of GJB2-related hearing loss. We suggest that other genes may be involved in the population

Homozygosity mapping and CDH23 mutation analysis in Iranian deaf families

Objective: Cadherin-related 23 (CDH23) gene encodes a cell�cell adhesion protein which is required for the proper development of hair cells. Previous studies have shown that different mutations in this gene are associated with Usher syndrome, autosomal recessive nonsyndromic deafness (DFNB12) and age-related hearing loss. In this study the contribution of CDH23 mutations in hearing loss has been investigated. Study design: The homosygosity mapping, using microsatellite markers linked to DFNB12 locus was performed for a population of 45 GJB2 negative Iranian families with autosomal recessive non-syndromic form of hearing loss. Coding region and exon-intron boundaries of all 69 exons of the CDH23 gene were investigated using Sanger sequencing. Results: The homozygosity mapping showed co-segregation of the hearing loss with four STR markers linked to the DFNB12 locus in one family. Assessing pathogenicity of identified variations in this gene showed that previously reported mutation c.2968G > A (p.Asp990Asn) can be the cause of hearing loss in this family. Conclusion: This study suggests that CDH23 mutations may have a significant role in causing hearing loss in Iran. More studies should be performed to determine frequency of this gene in the Iranian population. © 2016 International Association of Physicians in Audiology

Laser Hair Removal

Laser hair removal is one of the most common non-surgical procedures performed in the United States. Excessive, unwanted hair can be seen in all ages, ethnicities and skin types and lasers can help provide a permanent reduction in hair growth. Professional and home-based laser and light systems are both currently available, with professional systems including the 694 nm ruby laser, 755 nm Alexandrite laser, the 800 nm diode laser, the long-pulsed 1,064 nm Neodymium doped: yttrium aluminum garnet (Nd:YAG) laser, intense pulsed light (IPL), and radiofrequency. While generally safe, side effects from laser hair removal are possible and should only be used by trained medical professionals after performing a thorough history and physical examination. This chapter will provide a succinct approach to laser hair removal, including but not limited to available modalities, patient selection, reported side effects and management of care