1. Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing
- Author
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Funari, Kim Ca, Antonio M. Lerario, Paulo Ferrez Collett-Solberg, Edoarda Vasco de Albuquerque Albuquerque, Andrew Dauber, Miura Sugayama Sm, Honjo Kawahira Rs, Bruna L Freire, Thais Kataoka Homma, Mirian Yumie Nishi, Jorge Aal, Alexsandra C. Malaquias, Arnhold Ijp, Gabriela A Vasques, and Débora Romeo Bertola
- Subjects
Male ,Candidate gene ,Pediatrics ,medicine.medical_specialty ,Ubiquitin-Protein Ligases ,Kinesins ,Cell Cycle Proteins ,Dwarfism ,Short stature ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Exome Sequencing ,Intellectual disability ,Humans ,Medicine ,Abnormalities, Multiple ,Prospective Studies ,030212 general & internal medicine ,Child ,Prospective cohort study ,Cyclin-Dependent Kinase Inhibitor p57 ,Exome sequencing ,Adenosine Triphosphatases ,biology ,business.industry ,Tumor Suppressor Proteins ,Histone-Lysine N-Methyltransferase ,medicine.disease ,Prenatal onset ,Actins ,DNA-Binding Proteins ,Repressor Proteins ,Cytoskeletal Proteins ,KMT2A ,Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases ,Infant, Small for Gestational Age ,Mutation ,Pediatrics, Perinatology and Child Health ,biology.protein ,Etiology ,Small for gestational age ,Transcriptional Elongation Factors ,medicine.symptom ,business ,Myeloid-Lymphoid Leukemia Protein - Abstract
Objective To perform a prospective genetic investigation using whole exome sequencing of a group of patients with syndromic short stature born small for gestational age of unknown cause. Study design For whole exome sequencing analysis, we selected 44 children born small for gestational age with persistent short stature, and additional features, such as dysmorphic face, major malformation, developmental delay, and/or intellectual disability. Seven patients had negative candidate gene testing based on clinical suspicion and 37 patients had syndromic conditions of unknown etiology. Results Of the 44 patients, 15 (34%) had pathogenic/likely pathogenic variants in genes already associated with growth disturbance: COL2A1 (n = 2), SRCAP (n = 2), AFF4, ACTG1, ANKRD11, BCL11B, BRCA1, CDKN1C, GINS1, INPP5K, KIF11, KMT2A, and POC1A (n = 1 each). Most of the genes found to be deleterious participate in fundamental cellular processes, such as cell replication and DNA repair. Conclusions The rarity and heterogeneity of syndromic short stature make the clinical diagnosis difficult. Whole exome sequencing allows the diagnosis of previously undiagnosed patients with syndromic short stature.
- Published
- 2019