A nonsense mutation of PEPD in four Amish children with prolidase deficiency
| Autor: | Douglas S S Kerr, Kenneth M. Kaufman, Sadamu Kurono, Vera Hupertz, Anil D'Souza, Hiroyuki Matsumoto, David L. Miller, Biji T. Kurien, David W. Lundgren, Heng Wang, Nisha C. Patel, Leah Nye, R. Hal Scofield, Andrew C. Porter, John Tumbush |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Dipeptidases Population Nonsense mutation DNA Mutational Analysis Hepatosplenomegaly Aspartate transaminase Gene mutation Biology Exon Skin Ulcer Genetics medicine Ethnicity Humans Abnormalities Multiple education Child Genetics (clinical) Family Health education.field_of_study Prolidase deficiency Base Sequence PEPD medicine.disease Pedigree Codon Nonsense Immunology Splenomegaly biology.protein Female medicine.symptom Hepatomegaly |
| Zdroj: | American journal of medical genetics. Part A. 140(6) |
| ISSN: | 1552-4825 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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