Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, MBC 75, PO Box 3354, Riyadh 11211, Saudi Arabia.
Eur J Pediatr. 2011 Jan;170(1):121-6. doi: 10.1007/s00431-010-1298-0. Epub 2010 Sep 24.
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.
迪格夫-梅尔乔尔-克劳斯综合征（DMC）是一种罕见的常染色体隐性遗传疾病，其特征是进行性脊椎骨骺发育不良和智力障碍的联合发生，其严重程度从轻度到重度不等。该疾病是由 18q12-12.1 染色体区域的 dymeclin（DYM）基因突变引起的。我们报告了两例具有 DMC 典型临床和影像学特征且无症状性寰枢椎脱位的同胞。检测到一个新的纯合剪接位点突变（IVS15+3G>T）。逆转录聚合酶链反应（RT-PCR）证实该突变影响正常剪接。据我们所知，这是沙特阿拉伯首例 DMC 的报道。我们患者中注意到的剪接突变与之前报道的病例进行了比较，支持 DYM 功能丧失是疾病发病机制的可能机制这一假说。总之，对于儿科医生和临床遗传学家来说，区分这种骨骼发育不良和黏多糖贮积症 IV 型（MPS IV）对于提供标准的患者护理和遗传咨询非常重要。
