Four novel PEPD alleles causing prolidase deficiency

Journal Article · Wed Jun 01 04:00:00 EDT 1994 · American Journal of Human Genetics; (United States)

OSTI ID:7075933

Ledoux, P; Scriver, C; Hechtman, P ^[1]

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1. 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), Journal Name: American Journal of Human Genetics; (United States) Vol. 54:6; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
550900 -- Pathology
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMINO ACIDS
AZOLES
CARBOXYLIC ACIDS
CHROMOSOMES
DISEASES
DNA SEQUENCING
ENZYMES
GENE AMPLIFICATION
GENE MUTATIONS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HUMAN CHROMOSOME 19
HUMAN CHROMOSOMES
HYDROLASES
HYDROXY ACIDS
HYDROXYPROLINE
METABOLIC DISEASES
METABOLISM
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HYDROLASES
POLYMERASE CHAIN REACTION
PROLINE
PROTEINS
PYRROLES
PYRROLIDINES
STRUCTURAL CHEMICAL ANALYSIS