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A nonsense mutation of PEPD in four Amish children with prolidase deficiency
Author(s) -
Wang Heng,
Kurien Biji T.,
Lundgren David,
Patel Nisha C.,
Kaufman K. M.,
Miller David L.,
Porter Andrew C.,
D'Souza Anil,
Nye Leah,
Tumbush John,
Hupertz Vera,
Kerr Douglas S.,
Kurono S.,
Matsumoto H.,
Scofield R. Hal
Publication year - 2006
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31134
Subject(s) - hepatosplenomegaly , nonsense mutation , frameshift mutation , compound heterozygosity , exon , missense mutation , biology , medicine , genetics , mutation , microbiology and biotechnology , gene , disease
Encoded by the peptidase D ( PEPD ) gene located at 19q12‐q13.11, prolidase is a ubiquitous cytosolic enzyme that catalyzes hydrolysis of oligopeptides with a C‐terminal proline or hydroxyproline. We describe here four Amish children with a severe phenotype of prolidase deficiency in the Geauga settlements of Ohio as the first report of prolidase deficiency in the Amish population as well as in the United States. The patients presented with infection, hepatosplenomegaly, or thrombocytopenia, in contrast to most cases previously reported in the literature, presenting with skin ulcers. All four patients had typical facial features, classic skin ulcers, and multisystem involvement. Recurrent infections, asthma‐like chronic reactive airway disease, hyperimmunoglobulins, hepatosplenomegaly with mildly elevated aspartate transaminase (AST), anemia, and thrombocytopenia were common and massive imidodipeptiduria was universal. Prolidase activity in our patients is nearly undetectable. Direct sequencing of PCR‐amplified genomic DNA for all of the exons from the four patients revealed the same homozygous single nucleotide mutation c.793 T > C in exon 11, resulting in a premature stop‐codon at amino acid residue 265 (p.R265X). It is speculated that the severe phenotype in these patients might be associated with the type of the PEPD gene mutation. © 2006 Wiley‐Liss, Inc.