Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss

Roxane Van Heurck,Pascal Senn,Maria Teresa Carminho-Rodrigues,Nils Guinand,Corinne Gehrig,Caterina Stafuzza,Lina Quteineh,Eva Hammar,Michel Guipponi,Ariane Paoloni-Giacobino,Helene Cao-Van,Emmanuelle Ranza,Marc Abramowicz

doi:10.3390/genes12081277

Abstract

Purpose: Hearing loss is characterized by an extensive genetic heterogeneity and remains a common disorder in children. Molecular diagnosis is of particular benefit in children, and permits the early identification of clinically-unrecognized hearing loss syndromes, which permits effective clinical management and follow-up, including genetic counselling. Methods: We performed whole-exome sequencing with the analysis of a panel of 189 genes associated with hearing loss in a prospective cohort of 61 children and 9 adults presenting mainly with isolated hearing loss. Results: The overall diagnostic rate using exome sequencing was 47.2% (52.5% in children; 22% in adults). In children with confirmed molecular results, 17/32 (53.2%) showed autosomal recessive inheritance patterns, 14/32 (43.75%) showed an autosomal dominant condition, and one case had X-linked hearing loss. In adults, the two patients showed an autosomal dominant inheritance pattern. Among the 32 children, 17 (53.1%) had nonsyndromic hearing loss and 15 (46.7%) had syndromic hearing loss. One adult was diagnosed with syndromic hearing loss and one with nonsyndromic hearing loss. The most common causative genes were STRC (5 cases), GJB2 (3 cases), COL11A1 (3 cases), and ACTG1 (3 cases). Conclusions: Exome sequencing has a high diagnostic yield in children with hearing loss and can reveal a syndromic hearing loss form before other organs/systems become involved, allowing the surveillance of unrecognized present and/or future complications associated with these syndromes.

Highlights

Almost one in 500 infants is affected by hearing loss (HL) [1,2]
Following written informed consent obtained from all adult patients and the parents or guardians of children, as well as health insurance approval, patients underwent whole-exome sequencing (WES) with a bioinformatic analysis of HL and an ear malformation updated panel ranging from 172 to 189 genes, including GJB2/GJB6
Our patients did not have any syndromic features to date and we considered that these mutations were related to autosomal dominant deafness 20/26 (MIM: 604717) [26,27,28]

Summary

Introduction

Almost one in 500 infants is affected by hearing loss (HL) [1,2]. The prevalence increases dramatically with age in adults, and it has been estimated that approximately one-half of all adults aged between 60 and 69 years and 80% of those over 80 years old suffer from HL [3]. More than one-half of congenital or early-onset, bilateral sensorineural (SN) cases are believed to have a genetic cause, with the remainder either acquired or idiopathic [1,4]. Genetic etiologies are further divided into isolated or syndromic HL (associated with dysmorphic features and/or additional medical problems). Hearing screenings are recommended for newborns, as early detection and diagnosis of HL has been proven to improve health outcomes [6]. Universal newborn hearing screening was recommended in 1998 in the European Consensus Statement on Neonatal Hearing Screening in Newborns [7] and introduced in Switzerland in 1999 under the auspices of the “Swiss Working Group: Hearing Screening in Newborns”

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