Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes

• Published in: American journal of medical genetics. Part A Vol. 143A; no. 21; pp. 2598 - 2603
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2007; Wiley-Liss
• Subjects: biochemical markers of bone turnover; Biological and medical sciences; bone mineral density; destructive vertebral changes; Female; Homozygote; Humans; Investigative techniques, diagnostic techniques (general aspects); Lamin Type A - genetics; LMNA; Mandible - abnormalities; Mandible - diagnostic imaging; mandibuloacral dysplasia; Medical genetics; Medical sciences; Middle Aged; Muscle, Skeletal - abnormalities; Muscle, Skeletal - diagnostic imaging; Mutation, Missense - genetics; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Osteoarticular system. Muscles; osteolysis; paraplegia; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Radiography; Human; Nervous system diseases; Dysplasia; destructive vertebral changes; mandibuloacral dysplasia; Motor system disorder; Biochemical marker; Vertebra; Osteolysis; Progressive; Paraplegia; Turnover; LMNA; biochemical markers of bone turnover; Bone mineral density; Mutation; Bone; Neurological disorder; Woman; Severe
• ISSN: 1552-4825; 1552-4833
• 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. © 2007 Wiley‐Liss, Inc.