Kosho Tomoki, Takahashi Jun, Momose Takashige, Nakamura Akinori, Sakurai Akihiro, Wada Takahito, Yoshida Kunihiro, Wakui Keiko, Suzuki Takefumi, Kasuga Kazuo, Nishimura Gen, Kato Hiroyuki, Fukushima Yoshimitsu
Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
Am J Med Genet A. 2007 Nov 1;143A(21):2598-603. doi: 10.1002/ajmg.a.31983.
A 56-year-old Japanese woman with mandibuloacral dysplasia and type A lipodystrophy is described. Mutation analysis identified a homozygous missense mutation (1585G > A) in exon 9 of the LMNA gene that replaces well-conserved residue alanine at position 529 to threonine (A529T). The woman showed, in addition to the usual clinical manifestations of the disorder, severe progressive skeletal changes: osteoporotic changes with multiple fractures; osteolysis of the right radius; and destructive changes of the vertebrae, leading to compression of the cervical spinal cord and paraplegia. Laboratory findings included markedly reduced bone mineral density; significantly increased urine N-telopeptide of collagen type I, an osteoclast marker; and normal serum bone specific alkaline phosphatase, an osteoblast marker. Regular follow up of adult patients with the disorder is desirable, including skeletal radiography, estimates of bone mineral density, and biochemical markers of bone turnover. Treatment with bisphosphonates to inhibit osteoclast activity is likely to be beneficial.
本文描述了一名56岁患有下颌骨发育不全和A型脂肪营养不良的日本女性。突变分析在LMNA基因第9外显子中鉴定出一个纯合错义突变（1585G > A），该突变将529位高度保守的丙氨酸残基替换为苏氨酸（A529T）。该女性除了具有该疾病常见的临床表现外，还出现了严重的进行性骨骼改变：骨质疏松伴多发骨折；右桡骨骨质溶解；以及椎体破坏，导致颈髓受压和截瘫。实验室检查结果包括骨密度显著降低；破骨细胞标志物I型胶原尿N-端肽显著升高；而成骨细胞标志物血清骨特异性碱性磷酸酶正常。对患有该疾病的成年患者进行定期随访是必要的，包括骨骼X线摄影、骨密度评估以及骨转换的生化标志物检测。使用双膦酸盐抑制破骨细胞活性的治疗可能有益。
