Recurrent Copy Number Variants Associated with Syndromic Short Stature of Unknown Cause

Autor(es):Mostrar menos -

Homma, Thais K. ^{[1, 2]} ; Krepischi, Ana C. V. ^[3] ; Furuya, Tatiane K. ^[4] ; Honjo, Rachel S. ^[5] ; Malaquias, Alexsandra C. ^[6] ; Bertola, Debora R. ^[5] ; Costa, Silvia S. ^[3] ; Canton, Ana P. ^[1] ; Roela, Rosimeire A. ^[4] ; Freire, Bruna L. ^[2] ; Kim, Chong A. ^[5] ; Rosenberg, Carla ^[3] ; Jorge, Alexander A. L. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Unidade Endocrinol Genet, Lab Endocrinol Celular & Mol LIM25, Disciplina Endocrinol, Fac Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Hosp Clin, Lab Hormonios & Genet Mol LIM42, Unidade Endocrinol Desenvolvimento, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Radiol & Oncol, Ctr Invest Translac Oncol, Fac Med, Lab Oncol Expt LIM24, Inst Canc Estado Sao Paulo C, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med, Hosp Clin, Unidade Genet, Inst Crianca, Sao Paulo - Brazil

^[6] Irmandade Santa Casa Misericordia Sao Paulo, Fac Ciencias Med Santa Casa Sao Paulo, Dept Pediat, Unidade Endocrinol Pediat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Hormone Research in Paediatrics; v. 89, n. 1, p. 13-21, 2018.
• Citações Web of Science: 5

Resumo

Background/Aims: Genetic imbalances are responsible for many cases of short stature of unknown etiology. This study aims to identify recurrent pathogenic copy number variants (CNVs) in patients with syndromic short stature of unknown cause. Methods: We selected 229 children with short stature and dysmorphic features, developmental delay, and/or intellectual disability, but without a recognized syndrome. All patients were evaluated by chromosomal microarray (array-based comparative genomic hybridization/single nucleotide polymorphism array). Additionally, we searched databases and previous studies to recover recurrent pathogenic CNVs associated with short stature. Results: We identified 32 pathogenic/probably pathogenic CNVs in 229 patients. By reviewing the literature, we selected 4 previous studies which evaluated CNVs in cohorts of patients with short stature. Taken together, there were 671 patients with short stature of unknown cause evaluated by chromosomal microarray. Pathogenic/probably pathogenic CNVs were identified in 87 patients (13%). Seven recurrent CNVs, 22q11.21, 15q26, 1p36.33, Xp22.33, 17p13.3, 1q21.1, 2q24.2, were observed. They are responsible for about 40% of all pathogenic/probably pathogenic genomic imbalances found in short stature patients of unknown cause. Conclusion: CNVs seem to play a significant role in patients with short stature. Chromosomal microarray should be used as a diagnostic tool for evaluation of growth disorders, especially for syndromic short stature of unknown cause. (C) 2017 S. Karger AG, Basel (AU)

• Processo FAPESP: 15/26980-7 - Causas genéticas de distúrbio de crescimento de início pré-natal
• Beneficiário: Thais Kataoka Homma
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/00898-1 - Desequilíbrios genômicos submicroscópicos em quadros clínicos específicos de anomalias congênitas e deficiência mental
• Beneficiário: Carla Rosenberg
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/03236-5 - Novas abordagens e metodologias na investigação genético-molecular dos distúrbios de crescimento e desenvolvimento puberal
• Beneficiário: Alexander Augusto de Lima Jorge
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs