Context: Mutations in the lamin A/C (LMNA) gene have been reported in a wide variety of disorders, including lipodystrophies, cardiomyopathy, muscular dystrophies, neuropathy, mandibuloacral dysplasia, restrictive dermopathy, and progeria. Objective: The objective of this study was to carry out mutational analysis of LMNA in a patient with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features. Design: The study design was a descriptive case report. Setting: The study was performed at a referral center. Patient: A 44-yr-old male of European descent with an autosomal recessive arthropathy syndrome affecting predominantly the distal femora and proximal tibia in the knee with tendinous calcifications was studied. He also had progeroid features, such as pinched nose and micrognathia, cataract, alopecia, generalized lipodystrophy, and sclerodermatous skin. Main Outcome Measures: The main outcome measures were mutational analysis of lamin A/C (LMNA) and its processing enzyme, zinc metalloproteinase (ZMPSTE24), as candidate genes. Results: We found a homozygous nucleotide substitution, 1718C>T, in exon 11 of the LMNA gene, resulting in substitution of a well-conserved residue serine at position 573 with leucine (S573L). This missense mutation only affects lamin A, not lamin C, because the alternative splicing site is located in exon 10. Immunofluorescence staining of the nuclei from his skin fibroblasts showed occasional misshapen morphology. Conclusions: The S573L homozygous LMNA mutation is associated with a novel phenotype of arthropathy, tendinous calcifications, and progeroid features distinct from the acroosteolysis previously reported in patients with mandibuloacral dysplasia caused by LMNA or ZMPSTE24 mutations. Thus, arthropathy with tendinous calcifications can be added to the growing list of disorders associated with LMNA mutations.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical