| Title: | Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency |
| Author(s): | Agarwal AK; Zhou XJ; Hall RK; Nicholls K; Bankier A; Van Esch H; Fryns JP; Garg A; |
| Address: | "From the Division of Nutrition and Metabolic Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390-9052, USA" |
| ISSN/ISBN: | 1081-5589 (Print) 1081-5589 (Linking) |
| Abstract: | "BACKGROUND: Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by skeletal abnormalities such as hypoplasia of the mandible and clavicles and acro-osteolysis. Other features include cutaneous atrophy and lipodystrophy. Two genetic loci are known for MAD: lamin A/C (LMNA), encoding structural nuclear lamina proteins, and zinc metalloproteinase (ZMPSTE24), a membrane-bound endoprotease involved in post-translational proteolytic cleavage of carboxy terminal residues of prelamin A to form mature lamin A. METHODS: Mutational analysis of ZMPSTE24 in an additional patient with MAD and determination of functional activity of mutant ZMPSTE24 in a yeast growth arrest pheromone diffusion (halo) assay. RESULTS: We previously reported a Belgian woman with MAD who had ZMPSTE24 mutations and died of complications of chronic renal failure at the age of 27.5 years. We now report a 37-year-old Australian man with MAD who also had compound heterozygous mutations in the ZMPSTE24 gene, a null mutation, Phe361fsX379, and a missense mutation, Asn265Ser, which is partially active in the yeast complementation assay. He also developed end-stage renal disease and, despite receiving a cadaveric renal transplantation, died prematurely at the age of 37 years. Renal biopsies of both patients revealed focal segmental glomerulosclerosis, and the female patient had the collapsing variant. CONCLUSION: These observations suggest focal segmental glomerulosclerosis as a phenotypic manifestation in patients with ZMPSTE24 deficiency" |
| Keywords: | "Acro-Osteolysis/*genetics/pathology Adult Amino Acid Sequence Clavicle/abnormalities Craniofacial Abnormalities/*genetics/pathology DNA Mutational Analysis Extremities/*pathology Fatal Outcome Female Glomerulosclerosis, Focal Segmental/*genetics/pathology;" |
| Notes: | "MedlineAgarwal, Anil K Zhou, Xin J Hall, Roger K Nicholls, Kathy Bankier, Agnes Van Esch, Hilde Fryns, Jean-Pierre Garg, Abhimanyu eng R01-DK54387/DK/NIDDK NIH HHS/ Case Reports Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2006/12/13 J Investig Med. 2006 May; 54(4):208-13. doi: 10.2310/6650.2006.05068" |
