Exome Sequencing Identifies Multiple Genetic Diagnoses in Children with Syndromic Growth Disorders.

Autor: Rezende RC; Laboratorio de Endocrinologia Celular e Molecular LIM25, Unidade de Endocrinologia Genetica/Faculdade de Medicina da Universidade de Sao Paulo (FMUSP)/Hospital das Clinicas da Universidade de Sao Paulo, Sao Paulo, SP, Brazil., Menezes de Andrade NL; Laboratorio de Endocrinologia Celular e Molecular LIM25, Unidade de Endocrinologia Genetica/Faculdade de Medicina da Universidade de Sao Paulo (FMUSP)/Hospital das Clinicas da Universidade de Sao Paulo, Sao Paulo, SP, Brazil., Branco Dantas NC; Laboratorio de Endocrinologia Celular e Molecular LIM25, Unidade de Endocrinologia Genetica/Faculdade de Medicina da Universidade de Sao Paulo (FMUSP)/Hospital das Clinicas da Universidade de Sao Paulo, Sao Paulo, SP, Brazil., de Polli Cellin L; Laboratorio de Endocrinologia Celular e Molecular LIM25, Unidade de Endocrinologia Genetica/Faculdade de Medicina da Universidade de Sao Paulo (FMUSP)/Hospital das Clinicas da Universidade de Sao Paulo, Sao Paulo, SP, Brazil., Victorino Krepischi AC; Human Genome and Stem Cell Research Center, Institute of Biosciences, University of Sao Paulo, Sao Paulo, SP, Brazil., Lerario AM; Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI., de Lima Jorge AA; Laboratorio de Endocrinologia Celular e Molecular LIM25, Unidade de Endocrinologia Genetica/Faculdade de Medicina da Universidade de Sao Paulo (FMUSP)/Hospital das Clinicas da Universidade de Sao Paulo, Sao Paulo, SP, Brazil. Electronic address: alexj@usp.br.
Jazyk: angličtina
Zdroj: The Journal of pediatrics [J Pediatr] 2024 Feb; Vol. 265, pp. 113841. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1016/j.jpeds.2023.113841
Abstrakt: Objective: To evaluate the presence of multiple genetic diagnoses in syndromic growth disorders.
Study Design: We carried out a cross-sectional study to evaluate 115 patients with syndromic tall (n = 24) or short stature (n = 91) of unknown cause from a tertiary referral center for growth disorders. Exome sequencing was performed to assess germline single nucleotide, InDel, and copy number variants. All variants were classified according to ACMG/AMP guidelines. The main outcome measured was the frequency of multiple genetic diagnoses in a cohort of children with syndromic growth disorders.
Results: The total diagnostic yield of the cohort was 54.8% (63/115). Six patients had multiple genetic diagnoses (tall stature group = 2; short stature group = 4). The proportion of multiple diagnoses within total cases was 5.2% (6/115), and within solved cases was 9.5% (6/63). No characteristics were significantly more frequent when compared with patients with single or multiple genetic findings. Among patients with multiple diagnoses, 3 had syndromes with overlapping clinical features, and the others had syndromes with distinct phenotypes.
Conclusion: Recognition of multiple genetic diagnoses as a possibility in complex cases of syndromic growth disorders opens a new perspective on treatment and genetic counseling for affected patients, defying the medical common sense of trying to fit all findings into one diagnosis.
Competing Interests: Declaration of Competing Interest Funding sources: Supported by the Sao Paulo Research Foundation (FAPESP) (2013/03236-5 and 2022/10107-6 to A.A.L.J.); by the National Council for Scientific and Technological Development (CNPq) (303294/2020-5 to A.A.L.J.), and by the Coordination of Superior Level Staff Improvement (CAPES) (Finance Code 001 to R.C.R, N.L.M.A., N.C.B.D., and L.P.C.). AALJ has received speaker fees from Novo Nordisk and Pfizer, has independent research grant from BioMarin and has received consulting fees from Novo Nordisk. The other authors declare that they have no competing financial interest to declare.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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