RESUMEN
Heterogeneous clinical and neuropsychological features, such as intellectual disability, developmental and language delay, hypotonia, and, to a lesser extent, microcephaly that is present in about the half of the reported patients, characterize the 3q29 microduplication syndrome with usually a milder phenotype compared with the corresponding 3q29 microdeletion syndrome. The duplications described so far range from 2.3â¯Mb to 1.6â¯Mb, spanning from TFRC to BDH1 genes. Here we report on two patients with overlapping interstitial duplications of the 3q29 region differing in size. Patient 1 harboured a common-seized 3q29 microduplication spanning â¼1.6â¯Mb, while patient 2 carried a very small 3q29 microduplication of 448.8â¯Kb encompassing only two genes, DLG1 and BDH1. Both patients presented clinical characteristics similar to those reported in the literature in 3q29 microduplication syndrome. Interestingly, heterotopic gray matter nodules were found along the right lateral ventricle on brain MRI in patient 1, thus expanding the neuroradiological phenotype in 3q29 microduplication syndrome, while patient 2 allowed us to define with more precision the smallest region of overlap (SRO). Gene content analysis of the duplicated region suggests that gain-of-dosage of DLG1 and BDH1 may be a good candidate for the main clinical features of this syndrome.
Asunto(s)
Trastornos de los Cromosomas/genética , Duplicación Cromosómica/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Niño , Trastornos de los Cromosomas/diagnóstico por imagen , Trastornos de los Cromosomas/patología , Homólogo 1 de la Proteína Discs Large , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Hidroxibutirato Deshidrogenasa/genética , Masculino , Proteínas de la Membrana/genética , Receptores de Transferrina/genéticaAsunto(s)
Cauda Equina/patología , Síndrome de Cockayne/diagnóstico , Nervios Craneales/patología , Síndrome de Cockayne/complicaciones , Síndrome de Cockayne/genética , Enzimas Reparadoras del ADN/genética , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Factores de Transcripción/genéticaRESUMEN
Smith-Magenis syndrome (SMS) is caused by an interstitial microdeletion of chromosome 17p11.2. A few patients with the typical SMS phenotype have RAI1 gene mutations. The syndrome is characterized by minor craniofacial anomalies, short stature, sleep disturbances, behavioural and neurocognitive abnormalities, as well as variable multisystemic manifestations. Periventricular nodular heterotopia (PNH) is a genetically heterogeneous neuronal migration disorder characterized by subependymal heterotopic nodules, and is variably associated with other brain malformations, epileptic seizures and intellectual disability. Here we report on two patients harboring deletions of the 17p11.2 region in whom the SMS typical phenotype was associated with bilateral PNH. Our observations expand the spectrum of chromosomal rearrangements associated with PNH and indicate that abnormal neuronal migration may contribute to the neurocognitive phenotype of SMS.
Asunto(s)
Heterotopia Nodular Periventricular/patología , Síndrome de Smith-Magenis/patología , Adolescente , Encéfalo/diagnóstico por imagen , Preescolar , Deleción Cromosómica , Cromosomas Humanos Par 17/genética , Humanos , Imagen por Resonancia Magnética , Masculino , RadiografíaRESUMEN
Mutations in neuronal voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A may play an important role in the etiology of neurological diseases and psychiatric disorders, besides various types of epilepsy. Here we describe a 3-year-old boy with autistic features, language delay, microcephaly and no history of seizures. Array-CGH analysis revealed an interstitial deletion of ~291.9kB at band 2q24.3 disrupting the entire SCN2A gene and part of SCN3A. We discuss the effects of haploinsufficiency of SCN2A and SCN3A on the genetic basis of neurodevelopmental and neurobehavioral disorders and we propose that this haploinsufficiency may be associated not only with epilepsy, but also with autistic features.
Asunto(s)
Anomalías Múltiples/diagnóstico , Trastorno Autístico/diagnóstico , Deleción Cromosómica , Microcefalia/diagnóstico , Canal de Sodio Activado por Voltaje NAV1.2/genética , Canal de Sodio Activado por Voltaje NAV1.3/genética , Trastornos Psicomotores/diagnóstico , Canales de Sodio/genética , Anomalías Múltiples/genética , Trastorno Autístico/genética , Preescolar , Cromosomas Humanos Par 2 , Hibridación Genómica Comparativa , Haploinsuficiencia , Humanos , Trastornos del Desarrollo del Lenguaje/diagnóstico , Trastornos del Desarrollo del Lenguaje/genética , Masculino , Microcefalia/genética , Trastornos Psicomotores/genética , Convulsiones/diagnóstico , Convulsiones/genéticaRESUMEN
The complete affiliations of two authors appeared incorrectly. The affiliations of A. Selicorni and D. Milani should be given as.
RESUMEN
Cohen syndrome is an autosomal recessive disorder with variability in the clinical manifestations, characterized by developmental delay, visual disability, facial dysmorphisms and intermittent neutropenia. We described a cohort of 10 patients affected by Cohen syndrome from nine Italian families ranging from 5 to 52 years at assessment. Characteristic age related facial changes were well documented. Visual anomalies, namely retinopathy and myopia, were present in 9/10 patients (retinopathy in 9/10 and myopia in 8/10). Truncal obesity has been described in all patients older than 6 years (8/8). DNA samples from all patients were analyzed for mutations in COH1 by DHPLC. We detected 15 COH1 alterations most of them were truncating mutations, only one being a missense change. Partial gene deletions have been found in two families. Most mutations were private. Two were already reported in the literature just once. A single base deletion leading to p.T3708fs3769, never reported before, was found in three apparently unrelated families deriving from a restricted area of the Veneto's lowland, between Padova town and Tagliamento river, in heterozygous state. Given the geographical conformation of this region, which is neither geographically or culturally isolated, a recent origin of the mutation could be hypothesized.