title: Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan. ktomoki@hsp.md.shinshu-u.ac.jp
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosho
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.forename: Takashige
authors.initials: T
authors.lastname: Momose
authors.forename: Akinori
authors.initials: A
authors.lastname: Nakamura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sakurai
authors.forename: Takahito
authors.initials: T
authors.lastname: Wada
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yoshida
authors.forename: Keiko
authors.initials: K
authors.lastname: Wakui
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kasuga
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Fukushima
mesh_terms: D005260:Female; D006720:Homozygote; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008334:Mandible / Q000002:abnormalities* / Q000000981:diagnostic imaging; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000002:abnormalities* / Q000000981:diagnostic imaging; D020125:Mutation, Missense / Q000235:genetics*; D011859:Radiography
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A