CONTEXT: Mandibuloacral dysplasia (MAD) is a rare autosomal recessive progeroid 
syndrome due to mutations in genes encoding nuclear lamina proteins, lamins A/C 
(LMNA) or prelamin A processing enzyme, and zinc metalloproteinase (ZMPSTE24).
OBJECTIVE: The aim of the study was to investigate the underlying genetic and 
molecular basis of the phenotype of a 7-yr-old girl with MAD belonging to a 
consanguineous pedigree and with severe progeroid features and lipodystrophy.
DESIGN AND PATIENT: The patient developed mandibular hypoplasia during infancy 
and joint stiffness, skin thinning, and mottled hyperpigmentation at 15 months. 
Progressive clavicular hypoplasia, acroosteolysis, and severe loss of hair from 
the temporal and occipital areas were noticed at 3 yr. At 5 yr, cranial sutures 
were still open and lipodystrophy of the limbs was prominent. GH therapy from 
the ages of 3-7 yr did not improve the short stature. Severe joint contractures 
resulted in abnormal posture and decreased mobility. We studied her skin 
fibroblasts for nuclear morphology and immunoblotting and determined the in 
vitro effects of various pharmacological interventions on fibroblasts.
RESULTS: LMNA gene sequencing revealed a homozygous missense mutation, 
c.1579C>T, p.Arg527Cys. Immunoblotting of skin fibroblast lysate with lamin A/C 
antibody revealed no prelamin A accumulation. Immunofluorescence staining of the 
nuclei for lamin A/C in fibroblasts revealed marked nuclear morphological 
abnormalities. This abnormal phenotype could not be rescued with inhibitors of 
farnesyl transferase, geranylgeranyl transferase, or histone deacetylase.
CONCLUSION: Severe progeroid features in MAD could result from LMNA mutation, 
which does not lead to accumulation of prenylated lamin A or prelamin A.