Thais K Homma1,2, Ana C V Krepischi3, Tatiane K Furuya4, Rachel S Honjo5, Alexsandra C Malaquias6, Debora R Bertola5, Silvia S Costa3, Ana P Canton1, Rosimeire A Roela4, Bruna L Freire2, Chong A Kim5, Carla Rosenberg3, Alexander A L Jorge1,2. 1. Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil. 2. Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM42, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil. 3. Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo (IB-USP), Sao Paulo, Brazil. 4. Laboratorio de Oncologia Experimental LIM24, Departamento de Radiologia e Oncologia, Centro de Investigação Translacional em Oncologia do Instituto do Cancer do Estado de Sao Paulo (CTO/ICESP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Sao Paulo, Brazil. 5. Unidade de Genetica do Instituto da Criança, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil. 6. Unidade de Endocrinologia Pediatrica, Departamento de Pediatria, Irmandade da Santa Casa de Misericórdia de São Paulo, Faculdade de Ciências Médicas da Santa Casa de São Paulo, Sao Paulo, Brazil.
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.
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.
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
Authors: Emily Cottrell; Claudia P Cabrera; Miho Ishida; Sumana Chatterjee; James Greening; Neil Wright; Artur Bossowski; Leo Dunkel; Asma Deeb; Iman Al Basiri; Stephen J Rose; Avril Mason; Susan Bint; Joo Wook Ahn; Vivian Hwa; Louise A Metherell; Gudrun E Moore; Helen L Storr Journal: Eur J Endocrinol Date: 2020-12 Impact factor: 6.664