Ana P M Canton1, Sílvia S Costa1, Tatiane C Rodrigues1, Debora R Bertola2, Alexsandra C Malaquias1, Fernanda A Correa1, Ivo J P Arnhold1, Carla Rosenberg1, Alexander A L Jorge3. 1. Unidade de Endocrinologia GeneticaLaboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 5° Andar Sala 5340, CEP 01246-903 Sao Paulo, BrazilDepartamento de Genetica e Biologia EvolutivaInstituto de Biociencias da Universidade de Sao Paulo, 05508-900 Sao Paulo, BrazilUnidade de GeneticaInstituto da Crianca, Faculdade de Medicina da Universidade de Sao Paulo, 05403-000 Sao Paulo, BrazilUnidade de Endocrinologia do DesenvolvimentoLaboratorio de Hormonios e Genetica Molecular LIM/42 do Hospital das Clinicas, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, 05403-900 Sao Paulo, Brazil. 2. Unidade de Endocrinologia GeneticaLaboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 5° Andar Sala 5340, CEP 01246-903 Sao Paulo, BrazilDepartamento de Genetica e Biologia EvolutivaInstituto de Biociencias da Universidade de Sao Paulo, 05508-900 Sao Paulo, BrazilUnidade de GeneticaInstituto da Crianca, Faculdade de Medicina da Universidade de Sao Paulo, 05403-000 Sao Paulo, BrazilUnidade de Endocrinologia do DesenvolvimentoLaboratorio de Hormonios e Genetica Molecular LIM/42 do Hospital das Clinicas, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, 05403-900 Sao Paulo, BrazilUnidade de Endocrinologia GeneticaLaboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 5° Andar Sala 5340, CEP 01246-903 Sao Paulo, BrazilDepartamento de Genetica e Biologia EvolutivaInstituto de Biociencias da Universidade de Sao Paulo, 05508-900 Sao Paulo, BrazilUnidade de GeneticaInstituto da Crianca, Faculdade de Medicina da Universidade de Sao Paulo, 05403-000 Sao Paulo, BrazilUnidade de Endocrinologia do DesenvolvimentoLaboratorio de Hormonios e Genetica Molecular LIM/42 do Hospital das Clinicas, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, 05403-900 Sao Paulo, Brazil. 3. Unidade de Endocrinologia GeneticaLaboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 5° Andar Sala 5340, CEP 01246-903 Sao Paulo, BrazilDepartamento de Genetica e Biologia EvolutivaInstituto de Biociencias da Universidade de Sao Paulo, 05508-900 Sao Paulo, BrazilUnidade de GeneticaInstituto da Crianca, Faculdade de Medicina da Universidade de Sao Paulo, 05403-000 Sao Paulo, BrazilUnidade de Endocrinologia do DesenvolvimentoLaboratorio de Hormonios e Genetica Molecular LIM/42 do Hospital das Clinicas, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo, 05403-900 Sao Paulo, Brazil alexj@usp.br.
Abstract
BACKGROUND: The etiology of prenatal-onset short stature with postnatal persistence is heterogeneous. Submicroscopic chromosomal imbalances, known as copy number variants (CNVs), may play a role in growth disorders. OBJECTIVE: To analyze the CNVs present in a group of patients born small for gestational age (SGA) without a known cause. PATIENTS AND METHODS: A total of 51 patients with prenatal and postnatal growth retardation associated with dysmorphic features and/or developmental delay, but without criteria for the diagnosis of known syndromes, were selected. Array-based comparative genomic hybridization was performed using DNA obtained from all patients. The pathogenicity of CNVs was assessed by considering the following criteria: inheritance; gene content; overlap with genomic coordinates for a known genomic imbalance syndrome; and overlap with CNVs previously identified in other patients with prenatal-onset short stature. RESULTS: In 17 of the 51 patients, 18 CNVs were identified. None of these imbalances has been reported in healthy individuals. Nine CNVs, found in eight patients (16%), were categorized as pathogenic or probably pathogenic. Deletions found in three patients overlapped with known microdeletion syndromes (4q, 10q26, and 22q11.2). These imbalances are de novo, gene rich and affect several candidate genes or genomic regions that may be involved in the mechanisms of growth regulation. CONCLUSION: Pathogenic CNVs in the selected patients born SGA were common (at least 16%), showing that rare CNVs are probably among the genetic causes of short stature in SGA patients and revealing genomic regions possibly implicated in this condition.
BACKGROUND: The etiology of prenatal-onset short stature with postnatal persistence is heterogeneous. Submicroscopic chromosomal imbalances, known as copy number variants (CNVs), may play a role in growth disorders. OBJECTIVE: To analyze the CNVs present in a group of patients born small for gestational age (SGA) without a known cause. PATIENTS AND METHODS: A total of 51 patients with prenatal and postnatal growth retardation associated with dysmorphic features and/or developmental delay, but without criteria for the diagnosis of known syndromes, were selected. Array-based comparative genomic hybridization was performed using DNA obtained from all patients. The pathogenicity of CNVs was assessed by considering the following criteria: inheritance; gene content; overlap with genomic coordinates for a known genomic imbalance syndrome; and overlap with CNVs previously identified in other patients with prenatal-onset short stature. RESULTS: In 17 of the 51 patients, 18 CNVs were identified. None of these imbalances has been reported in healthy individuals. Nine CNVs, found in eight patients (16%), were categorized as pathogenic or probably pathogenic. Deletions found in three patients overlapped with known microdeletion syndromes (4q, 10q26, and 22q11.2). These imbalances are de novo, gene rich and affect several candidate genes or genomic regions that may be involved in the mechanisms of growth regulation. CONCLUSION: Pathogenic CNVs in the selected patients born SGA were common (at least 16%), showing that rare CNVs are probably among the genetic causes of short stature in SGA patients and revealing genomic regions possibly implicated in this condition.
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Authors: E Inzaghi; A Deodati; S Loddo; M Mucciolo; F Verdecchia; E Sallicandro; G Catino; M Cappa; A Novelli; S Cianfarani Journal: J Endocrinol Invest Date: 2021-07-13 Impact factor: 4.256