Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes.
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.
Kosho
Tomoki
T
Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan. ktomoki@hsp.md.shinshu-u.ac.jp
Takahashi
Jun
J
Momose
Takashige
T
Nakamura
Akinori
A
Sakurai
Akihiro
A
Wada
Takahito
T
Yoshida
Kunihiro
K
Wakui
Keiko
K
Suzuki
Takefumi
T
Kasuga
Kazuo
K
Nishimura
Gen
G
Kato
Hiroyuki
H
Fukushima
Yoshimitsu
Y
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
C494847:LMNA protein, human; D034904:Lamin Type A