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

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article
Data de publicação
2024
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PubMed
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MOSBY-ELSEVIER
Autores
KREPISCHI, Ana Cristina Victorino
LERARIO, Antonio Marcondes
Citação
JOURNAL OF PEDIATRICS, v.265, article ID 113841, 9p, 2024
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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. (J Pediatr 2024;265:113841)
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https://observatorio.fm.usp.br/handle/OPI/58750
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM