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Four novel PEPD alleles causing prolidase deficiency
P Ledoux1, C Scriver, P Hechtman
1Department of Biology, McGill University, Montreal, Quebec, Canada.
American Journal of Human Genetics
|June 1, 1994
Summary
Prolidase deficiency, a rare genetic disorder, is caused by mutations in the PEPD gene. This study identifies and characterizes four novel PEPD mutations, expanding the understanding of this condition.
Area of Science:
- Genetics
- Molecular Biology
- Biochemistry
Background:
- Prolidase deficiency (McKusick 170100) is a rare autosomal recessive disorder.
- It is characterized by iminodipeptiduria, skin ulcers, mental retardation, and recurrent infections.
- Mutations in the PEPD gene are the cause of this disorder.
Purpose of the Study:
- To characterize mutations in the PEPD gene in individuals with severe prolidase deficiency.
- To identify and describe novel PEPD alleles and their associated phenotypic expressions.
Main Methods:
- Reverse-transcription PCR (RT-PCR) amplification of cDNA.
- Single-strand conformation polymorphism (SSCP) analysis.
- Direct sequencing of cDNA and genomic DNA.
- Inverse PCR to identify intronic sequences.
Main Results:
- Four distinct PEPD mutations were identified in five individuals.
- Mutations included a missense mutation (G448R), a small in-frame deletion (delta E452/453), an exon 5 deletion, and an exon 7 deletion.
- Two splice acceptor mutations in introns 4 and 6 were identified as the cause of the exon deletions.
Conclusions:
- Severe prolidase deficiency results from multiple PEPD alleles.
- This study contributes to the cataloging of PEPD mutations and their phenotypic manifestations.