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

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: Hormone Research in Paediatrics; v. 89, n. 1, p. 13-21, 2018.
• Web of Science Citations: 5

Abstract

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)

• FAPESP's process: 15/26980-7 - Genetic causes of prenatal onset growth disorder
• Grantee: Thais Kataoka Homma
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 09/00898-1 - Submicroscopic genomic imbalances associated with specific congenital abnormalities and mental deficiency phenotypes
• Grantee: Carla Rosenberg
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/03236-5 - New approaches and methodologies in molecular-genetic studies of growth and pubertal development disorders
• Grantee: Alexander Augusto de Lima Jorge
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC