RESUMO
The product of the BCL11B (B-Cell Leukemia 11) gene is a bi-functional transcriptional regulator that can act as either a repressor or an activator. It plays an important role in the development of the nervous, immune, and cutaneous systems, and is also involved in dental and craniofacial development. BCL11B-Related Disorder (BCL11BRD) is a novel rare neurodevelopmental disorder associated with mutations in BCL11B. A total of 17 patients have been described in the literature thus far. The main symptoms of BCL11BRD include global developmental delay, speech impairment, dental anomalies, feeding difficulties, refractive errors, dysmorphic features, and immunological abnormalities. In this report, we describe two Canadian girls, with pathogenic de novo BCL11B variants, both diagnosed via exome sequencing. One of the patients had global developmental delay, dental anomalies, dysmorphic features, dyskinesia and hypotonia; the latter two symptoms have not been previously reported in patients with BCL11BRD. She also had dysgenesis of corpus callosum and dilatation of the frontal horns of lateral ventricles, a brain anomaly that has been previously reported in only one other patient. The second patient had developmental delay, dysmorphic features, spasticity in lower limbs and dental anomalies. Our report contributes to the knowledge of the BCL11BRD, expands the clinical phenotype, and can also aid with genetic counseling of newly identified patients.
Assuntos
Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Leucemia de Células B/genética , Fenótipo , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor/genética , Criança , Pré-Escolar , Anormalidades Craniofaciais/patologia , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Leucemia de Células B/patologia , MutaçãoRESUMO
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
Graphical abstract key: ADHD, attention deficit hyperactivity disorder; ASD, atrial septal defect; DD, developmental delay; EEG, electroencephalogram; Ht, height; ID, intellectual disability; OCD, obsessive-compulsive disorder; OFC, open fontanelle; PDA, patent ductus arteriosis; PFO, patent foramen ovale; VSD, ventricular septal defect; Wt, weight.
