Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency

Anil K. Agarwal, Xin J. Zhou, Roger K. Hall, Kathy Nicholls, Agnes Bankier, Hilde Van Esch, Jean Pierre Fryns, Abhimanyu Garg

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)208-213
Number of pages6
JournalJournal of Investigative Medicine
Volume54
Issue number4
DOIs
StatePublished - May 2006

Fingerprint

Lamin Type A
Focal Segmental Glomerulosclerosis
Yeast
Assays
Biopsy
Pheromones
Metalloproteases
Mutation
Chronic Kidney Failure
Zinc
Acro-Osteolysis
Genes
Yeasts
Nuclear Lamina
Membranes
Lipodystrophy
Clavicle
Genetic Loci
Missense Mutation
Nuclear Proteins

Keywords

  • Lamin A/C
  • Lipodystrophy
  • Mandibuloacral dysplasia
  • Progeroid syndrome
  • Zinc metalloproteinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency. / Agarwal, Anil K.; Zhou, Xin J.; Hall, Roger K.; Nicholls, Kathy; Bankier, Agnes; Van Esch, Hilde; Fryns, Jean Pierre; Garg, Abhimanyu.

In: Journal of Investigative Medicine, Vol. 54, No. 4, 05.2006, p. 208-213.

Research output: Contribution to journalArticle

Agarwal, Anil K. ; Zhou, Xin J. ; Hall, Roger K. ; Nicholls, Kathy ; Bankier, Agnes ; Van Esch, Hilde ; Fryns, Jean Pierre ; Garg, Abhimanyu. / Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency. In: Journal of Investigative Medicine. 2006 ; Vol. 54, No. 4. pp. 208-213.
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AU - Zhou, Xin J.

AU - Hall, Roger K.

AU - Nicholls, Kathy

AU - Bankier, Agnes

AU - Van Esch, Hilde

AU - Fryns, Jean Pierre

AU - Garg, Abhimanyu

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