RESUMEN

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.

Asunto(s)

Enanismo/genética , Secuenciación del Exoma , Anomalías Múltiples/genética , Actinas/genética , Adenosina Trifosfatasas/genética , Proteínas de Ciclo Celular/genética , Niño , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Proteínas del Citoesqueleto/genética , Proteínas de Unión al ADN/genética , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Recién Nacido Pequeño para la Edad Gestacional , Cinesinas/genética , Masculino , Mutación , Proteína de la Leucemia Mieloide-Linfoide/genética , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/genética , Estudios Prospectivos , Proteínas Represoras/genética , Factores de Elongación Transcripcional/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina-Proteína Ligasas/genética