RESUMO
Spinal muscular atrophy (SMA) is caused by homozygous deletion of the SMN1 gene in approximately 96% of cases. Four percent of SMA patients have a combination of the deletion or conversion on one allele and an intragenic mutation on the second one. We performed analysis of point mutations in a set of our patients with suspicion of SMA and without homozygous deletion of the SMN1 gene. A quantitative test determining SMN1 copy number (using real-time PCR and/or MLPA analysis) was performed in 301 patients and only 1 SMN1 copy was detected in 14 of them. When these 14 patients were screened for the presence of point mutations we identified 6 mutations, p.Y272C (in three patients) and p.T274I, p.I33IfsX6, and p.A188S (each in one case). The mutations p.I33IfsX6 and p.A188S were found in two SMAI patients and were not detected previously. Further, evaluation of the relationship between mutation type, copy number of the SMN2 gene and clinical findings was performed. Among our SMA patients with a SMN1 homozygous deletion, we found a family with two patients: the son with SMAII possesses 3 SMN2 copies and the nearly asymptomatic father has a homozygous deletion of SMN1 exon 7 and carries 4 SMN2 copies. Generally, our results illustrate that an increased SMN2 gene copy number is associated with a milder SMA phenotype.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Dosagem de Genes , Atrofia Muscular Espinal/genética , Proteínas do Tecido Nervoso/genética , Mutação Puntual/genética , Proteínas de Ligação a RNA/genética , Adolescente , Adulto , Pré-Escolar , DNA/genética , Éxons/genética , Deleção de Genes , Homozigoto , Humanos , Técnicas de Amplificação de Ácido Nucleico , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas do Complexo SMN , Proteína 1 de Sobrevivência do Neurônio Motor , Proteína 2 de Sobrevivência do Neurônio MotorRESUMO
BACKGROUND: Ultrafast T2-weighted (T2-W) MRI sequences are currently considered a routine technique for fetal MR imaging. Limited experience exists with fetal T1-weighted (T1-W) imaging techniques. OBJECTIVE: To determine MRI patterns of some fetal abdominal or haemorrhagic disorders with particular respect to the diagnostic value of T1-W images. MATERIALS AND METHODS: In addition to standard T2-W single-shot sequences, T1-W single-shot and/or multislice sequences were employed in 25 MR examinations performed in 23 fetuses between 20 and 36 weeks of gestation for more detailed assessment of liver, meconium-filled digestive tract, haemorrhage, or further characterization of a fetal abdominal mass. Diagnostic value and presence of motion artefacts on T1-W images was recorded in each case. RESULTS: T1-W images enabled superior delineation of fetal liver and large intestine. They provided additional diagnostic information in 9 (39%) of 23 fetuses. One false-positive and one false-negative MRI diagnosis of malrotation anomaly were encountered. Use of single-shot T1-W sequences reduced the occurrence of motion artefacts in 64%. CONCLUSION: Our results suggest that the specific signal properties of methaemoglobin, meconium and liver are sufficiently important for T1-W sequences to become a routine part of fetal MRI protocols when dealing with digestive tract anomalies, diaphragmatic and abdominal wall defects, intraabdominal masses, and fetal haemorrhage.
Assuntos
Abdome/anormalidades , Hemorragia/diagnóstico , Fígado/anormalidades , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal/métodos , Feminino , Humanos , Mecônio , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos RetrospectivosRESUMO
Gracile bone dysplasias constitute a group of disorders characterised by extremely slender bones with or without fractures. We report four newborns, two of whom showed multiple fractures. Two babies had osteocraniostenosis and one had features of oligohydramnios sequence. The diagnosis in the fourth newborn, which showed thin long bones and clavicles and extremely thin, poorly ossified ribs, is uncertain. Exact diagnosis of a gracile bone dysplasia is important for genetic counselling and medico-legal reasons.
