Dyggve–Melchior–Clausen syndrome: novel splice mutation with atlanto-axial subluxation
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Ola Khalifa & Faiqa Imtiaz & Nadia Al-Sakati & Khalid Al-Manea & Alain Verloes & Mohammed Al-Owain
- چاپ و سال / کشور: 2011
Description
Dyggve–Melchior–Clausen (DMC) syndrome is a rare autosomal recessive disorder characterized by the association of a progressive spondyloepimetaphyseal dysplasia and mental retardation ranging from mild to severe. The disorder results from mutations in the dymeclin (DYM) gene in the 18q12-12.1 chromosomal region. We report two siblings with classical clinical and radiological features of DMC and asymptomatic atlanto-axial dislocation. A novel homozygous splice-site mutation (IVS15+3G>T) was detected. Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed that this mutation affects normal splicing. To the best of our knowledge, this is the first report of DMC from Saudi Arabia. The splice mutation noted in our patients was compared to the previously reported cases and supports the hypothesis that loss of DYM function is the likely mechanism of disease pathogenesis. In conclusion, distinction between this type of skeletal dysplasia and Morquio disease (MPS IV) is important for paediatricians and clinical geneticist in providing standard patient care and genetic counselling.
Eur J Pediatr (2011) 170:121–126 DOI 10.1007/s00431-010-1298-0 Received: 3 July 2010 / Accepted: 8 September 2010 / Published online: 24 September 2010
