Asunto(s)
Cromosomas Humanos Par 16 , Hernias Diafragmáticas Congénitas , Diagnóstico Prenatal , Trisomía/diagnóstico , Aborto Eugénico , Adulto , Femenino , Hernia Diafragmática/complicaciones , Hernia Diafragmática/diagnóstico , Hernia Diafragmática/genética , Humanos , Embarazo , Diagnóstico Prenatal/estadística & datos numéricosRESUMEN
Megalencephalic leukoencephalopathy with subcortical cysts is a rare leukodystrophy characterized by macrocephaly and a slowly progressive clinical course marked by spasticity and cognitive decline. We report two full siblings with neuroimaging studies and clinical courses typical for megalencephalic leukoencephalopathy with subcortical cysts, in whom a pair of novel mutations in the MLC1 gene was identified. We review the current knowledge of this disorder in relation to the patients reported.
Asunto(s)
Quistes del Sistema Nervioso Central/genética , Anomalías Craneofaciales/genética , Demencia Vascular/genética , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/genética , Proteínas de la Membrana/genética , Adolescente , Quistes del Sistema Nervioso Central/diagnóstico , Niño , Anomalías Craneofaciales/diagnóstico , Demencia Vascular/diagnóstico , Femenino , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/diagnóstico , Humanos , MasculinoRESUMEN
Submicroscopic deletions involving chromosome 1q43-q44 result in cognitive impairment, microcephaly, growth restriction, dysmorphic features, and variable involvement of other organ systems. A consistently observed feature in patients with this deletion are the corpus callosal abnormalities (CCAs), ranging from thinning and hypoplasia to complete agenesis. Previous studies attempting to delineate the critical region for CCAs have yielded inconsistent results. We conducted a detailed clinical and molecular characterization of seven patients with deletions of chromosome 1q43-q44. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. Four patients had CCAs, and shared the smallest region of overlap that contains only three protein coding genes, CEP170, SDCCAG8, and ZNF238. One patient with a small deletion involving SDCCAG8 and AKT3, and another patient with an intragenic deletion of AKT3 did not have any CCA, implying that the loss of these two genes is unlikely to be the cause of CCA. CEP170 is expressed extensively in the brain, and encodes for a protein that is a component of the centrosomal complex. ZNF238 is involved in control of neuronal progenitor cells and survival of cortical neurons. Our results rule out the involvement of AKT3, and implicate CEP170 and/or ZNF238 as novel genes causative for CCA in patients with a terminal 1q deletion.
Asunto(s)
Agenesia del Cuerpo Calloso/genética , Deleción Cromosómica , Cromosomas Humanos Par 1 , Adolescente , Niño , Preescolar , Mapeo Cromosómico , Hibridación Genómica Comparativa , Femenino , Orden Génico , Humanos , Lactante , MasculinoRESUMEN
A 54-year-old woman presented with a nasal mass. Biopsy demonstrated undifferentiated tumor cells with extensive apoptosis and necrosis. Chromosome analysis identified a 46,XX,t(15;19)(q13;p13.1) pattern. Nuclear protein in testis (NUT) immunohistochemistry and fluorescence in situ hybridization confirmed NUT rearrangement. A Ewing sarcoma-based chemotherapy regimen and concurrent irradiation obtained a dramatic response; however, the patient died of her disease less than 7 months after initial diagnosis. NUT midline carcinomas are rare, aggressive tumors defined by rearrangement of the NUT gene on 15q14. A solitary translocation involving 15q14 is usually the sole chromosomal abnormality in these carcinomas. Immunohistochemical expression of NUT in the nuclei of non-germ cell tumors is theoretically diagnostic. More widespread use of a newly available NUT immunohistochemical stain will facilitate the diagnosis of NUT rearranged carcinomas. From the growing numbers of identified cases, effective targeted therapies can be developed.