Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss

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 m...

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Main Authors: Roxane Van Heurck, Maria Teresa Carminho-Rodrigues, Emmanuelle Ranza, Caterina Stafuzza, Lina Quteineh, Corinne Gehrig, Eva Hammar, Michel Guipponi, Marc Abramowicz, Pascal Senn, Nils Guinand, Helene Cao-Van, Ariane Paoloni-Giacobino
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/12/8/1277
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spelling doaj-88ac264084d646e1afe2d775b27460c02021-08-26T13:47:11ZengMDPI AGGenes2073-44252021-08-01121277127710.3390/genes12081277Benefits of Exome Sequencing in Children with Suspected Isolated Hearing LossRoxane Van Heurck0Maria Teresa Carminho-Rodrigues1Emmanuelle Ranza2Caterina Stafuzza3Lina Quteineh4Corinne Gehrig5Eva Hammar6Michel Guipponi7Marc Abramowicz8Pascal Senn9Nils Guinand10Helene Cao-Van11Ariane Paoloni-Giacobino12Division of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, SwitzerlandDivision of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, SwitzerlandDivision of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, SwitzerlandEar-Nose-Throat/Head and Neck Surgery Division, Geneva University Hospitals, 1205 Geneva, SwitzerlandDivision of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, SwitzerlandDivision of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, SwitzerlandDivision of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, SwitzerlandDivision of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, SwitzerlandDivision of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, SwitzerlandEar-Nose-Throat/Head and Neck Surgery Division, Geneva University Hospitals, 1205 Geneva, SwitzerlandEar-Nose-Throat/Head and Neck Surgery Division, Geneva University Hospitals, 1205 Geneva, SwitzerlandEar-Nose-Throat/Head and Neck Surgery Division, Geneva University Hospitals, 1205 Geneva, SwitzerlandDivision of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, SwitzerlandPurpose: 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.https://www.mdpi.com/2073-4425/12/8/1277isolated hearing lossdeafnessgeneticsmolecular diagnosischildrenwhole-exome sequencing
collection DOAJ
language English
format Article
sources DOAJ
author Roxane Van Heurck
Maria Teresa Carminho-Rodrigues
Emmanuelle Ranza
Caterina Stafuzza
Lina Quteineh
Corinne Gehrig
Eva Hammar
Michel Guipponi
Marc Abramowicz
Pascal Senn
Nils Guinand
Helene Cao-Van
Ariane Paoloni-Giacobino
spellingShingle Roxane Van Heurck
Maria Teresa Carminho-Rodrigues
Emmanuelle Ranza
Caterina Stafuzza
Lina Quteineh
Corinne Gehrig
Eva Hammar
Michel Guipponi
Marc Abramowicz
Pascal Senn
Nils Guinand
Helene Cao-Van
Ariane Paoloni-Giacobino
Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss
Genes
isolated hearing loss
deafness
genetics
molecular diagnosis
children
whole-exome sequencing
author_facet Roxane Van Heurck
Maria Teresa Carminho-Rodrigues
Emmanuelle Ranza
Caterina Stafuzza
Lina Quteineh
Corinne Gehrig
Eva Hammar
Michel Guipponi
Marc Abramowicz
Pascal Senn
Nils Guinand
Helene Cao-Van
Ariane Paoloni-Giacobino
author_sort Roxane Van Heurck
title Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss
title_short Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss
title_full Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss
title_fullStr Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss
title_full_unstemmed Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss
title_sort benefits of exome sequencing in children with suspected isolated hearing loss
publisher MDPI AG
series Genes
issn 2073-4425
publishDate 2021-08-01
description 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.
topic isolated hearing loss
deafness
genetics
molecular diagnosis
children
whole-exome sequencing
url https://www.mdpi.com/2073-4425/12/8/1277
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