Comprehensive Gene Panel Testing for Hearing Loss in Children: Understanding Factors Influencing Diagnostic Yield.

Autor: Yamamoto N; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Roberts Individualized Medical Genetics Center (RIMGC), Children's Hospital of Philadelphia, Philadelphia, PA; Division of Otolaryngology, Department of Surgical Specialties, National Center for Children's Health and Development, Tokyo, Japan; Division of Hearing and Balance Research, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan., Balciuniene J; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA; PerkinElmer Genomics, Pittsburgh, PA., Hartman T; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Roberts Individualized Medical Genetics Center (RIMGC), Children's Hospital of Philadelphia, Philadelphia, PA., Diaz-Miranda MA; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Bedoukian E; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Roberts Individualized Medical Genetics Center (RIMGC), Children's Hospital of Philadelphia, Philadelphia, PA., Devkota B; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Roberts Individualized Medical Genetics Center (RIMGC), Children's Hospital of Philadelphia, Philadelphia, PA., Lawrence A; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Roberts Individualized Medical Genetics Center (RIMGC), Children's Hospital of Philadelphia, Philadelphia, PA., Golenberg N; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Patel M; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Tare A; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Chen R; Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Schindler E; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Roberts Individualized Medical Genetics Center (RIMGC), Children's Hospital of Philadelphia, Philadelphia, PA., Choi J; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Roberts Individualized Medical Genetics Center (RIMGC), Children's Hospital of Philadelphia, Philadelphia, PA., Kaur M; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Roberts Individualized Medical Genetics Center (RIMGC), Children's Hospital of Philadelphia, Philadelphia, PA., Charles S; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Chen J; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Fanning EA; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Dechene E; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Cao K; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Jill MR; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Rajagopalan R; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Bayram Y; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Dulik MC; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Germiller J; Division of Pediatric Otolaryngology, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Otorhinolaryngology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Conlin LK; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Krantz ID; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA; Roberts Individualized Medical Genetics Center (RIMGC), Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Luo M; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Electronic address: luom@email.chop.edu.
Jazyk: angličtina
Zdroj: The Journal of pediatrics [J Pediatr] 2023 Nov; Vol. 262, pp. 113620. Date of Electronic Publication: 2023 Jul 19.
DOI: 10.1016/j.jpeds.2023.113620
Abstrakt: Objective: To evaluate factors influencing the diagnostic yield of comprehensive gene panel testing (CGPT) for hearing loss (HL) in children and to understand the characteristics of undiagnosed probands.
Study Design: This was a retrospective cohort study of 474 probands with childhood-onset HL who underwent CGPT between 2016 and 2020 at a single center. Main outcomes and measures included the association between clinical variables and diagnostic yield and the genetic and clinical characteristics of undiagnosed probands.
Results: The overall diagnostic yield was 44% (209/474) with causative variants involving 41 genes. While the diagnostic yield was high in the probands with congenital, bilateral, and severe HL, it was low in those with unilateral, noncongenital, or mild HL; cochlear nerve deficiency; preterm birth; neonatal intensive care unit admittance; certain ancestry; and developmental delay. Follow-up studies on 49 probands with initially inconclusive CGPT results changed the diagnostic status to likely positive or negative outcomes in 39 of them (80%). Reflex to exome sequencing on 128 undiagnosed probands by CGPT revealed diagnostic findings in 8 individuals, 5 of whom had developmental delays. The remaining 255 probands were undiagnosed, with 173 (173/255) having only a single variant in the gene(s) associated with autosomal recessive HL and 28% (48/173) having a matched phenotype.
Conclusion: CGPT efficiently identifies the genetic etiologies of HL in children. CGPT-undiagnosed probands may benefit from follow-up studies or expanded testing.
Competing Interests: Declaration of Competing Interest This work was partially supported by endowed funds in the Roberts Individualized Medical Genetics Center (RIMGC). The authors declare no conflicts of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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