Four novel PEPD alleles causing prolidase deficiency
- McGill Univ., Montreal (Canada)
Mutations at the PEPD locus cause prolidase (an enzyme specific for proline- and hydroxyproline-terminated dipeptides) deficiency (McKusick 170100), a rare autosomal recessive disorder characterized by iminodipeptiduria, skin ulcers, mental retardation, and recurrent infections. Four PEPD mutations from five severely affected individuals were characterized by analysis of reverse-transcribed, PCR-amplified (RT-PCR) cDNA. The authors used SSCP analysis on four overlapping cDNA fragments covering the entire coding region of the PEPD gene and detected abnormal SSCP bands for the fragments spanning all or part of exons 13-15 in three of the probands. Direct sequencing of the mutant cDNAs showed a G[yields]A, 1342 substitution (G448R) in two patients and a 3-bp deletion ([Delta]E452 or [Delta]E453) in another. In the other two probands the amplified products were of reduced size. Direct sequencing of these mutant cDNAs revealed a deletion of exon 5 in one patient and of exon 7 in the other. Intronic sequences flanking exons 5 and 7 were identified using inverse PCR followed by direct sequencing. Conventional PCR and direct sequencing then established the intron-exon borders of the mutant genomic DNA revealing two splice acceptor mutations: a G[yields]C substitution at position -1 of intron 4 and an A[yields]G substitution at position -2 of intron 6. The results indicate that the severe form of prolidase deficiency is caused by multiple PEPD alleles. In this report the authors attempt to begin the process of describing these alleles and cataloging their phenotype expression. 31 refs., 8 figs., 2 tabs.
- OSTI ID:
- 7075933
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 54:6; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HYDROXYPROLINE
METABOLISM
PEPTIDE HYDROLASES
GENE MUTATIONS
PROLINE
DNA SEQUENCING
HUMAN CHROMOSOME 19
METABOLIC DISEASES
POLYMERASE CHAIN REACTION
AMINES
AMINO ACIDS
AZOLES
CARBOXYLIC ACIDS
CHROMOSOMES
DISEASES
ENZYMES
GENE AMPLIFICATION
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HUMAN CHROMOSOMES
HYDROLASES
HYDROXY ACIDS
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PYRROLES
PYRROLIDINES
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics
550900 - Pathology