Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing

Autor: 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, Débora Romeo Bertola
Rok vydání: 2019
Předmět:
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
Zdroj: The Journal of Pediatrics. 215:192-198
ISSN: 0022-3476
DOI: 10.1016/j.jpeds.2019.08.024
Popis: 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.
Databáze: OpenAIRE
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