RESUMO
Diagnostic exome sequencing (DES) has aided delineation of the phenotypic spectrum of rare genetic etiologies of intellectual disability (ID). A SET domain containing 5 gene (SETD5) phenotype of ID and dysmorphic features has been previously described in relation to patients with 3p25.3 deletions and in a few individuals with de novo sequence alterations. Herein, we present additional patients with pathogenic SETD5 sequence alterations. The majority of patients in this cohort and previously reported have developmental delay, behavioral/psychiatric issues, and variable hand and skeletal abnormalities. We also present an apparently unaffected carrier mother of an affected individual and a carrier mother with normal intelligence and affected twin sons. We suggest that the phenotype of SETD5 is more complex and variable than previously presented. Therefore, many features and presentations need to be considered when evaluating a patient for SETD5 alterations through DES.
Assuntos
Transtornos Dismórficos Corporais/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Metiltransferases/genética , Adolescente , Adulto , Transtornos Dismórficos Corporais/diagnóstico , Transtornos Dismórficos Corporais/fisiopatologia , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 3/genética , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Penetrância , Fenótipo , Sequenciamento do Exoma , Adulto JovemRESUMO
A prospective multicentre study was performed to identify patients with fetal choroid plexus cysts and examine the association between choroid plexus cysts and chromosome abnormalities in the context of variables such as maternal age, serum triple-screen results, race, other prenatally-identified fetal anomalies and cyst characteristics. A total of 18 437 scans were performed in 5 centres and 257 fetuses were identified with choroid plexus cysts. Outcome was available on 250 patients, and of these, chromosomal abnormalities were detected in a total of 13 (5.2 per cent) fetuses. 26 patients in the group had additional ultrasound abnormalities, and 8 of these had fetal chromosome abnormalities. Among the 224 patients with isolated choroid plexus cysts, 5 (2.2 per cent) were found to have chromosomal abnormalities. All cases with identified chromosomal abnormalities were associated with an additional risk factor, such as other ultrasound findings, advanced maternal age or abnormal maternal serum triple-screen results.