A nonsense mutation of PEPD in four Amish children with prolidase deficiency.
A nonsense mutation of PEPD in four Amish children with prolidase deficiency.
复制标题
四名患有脯氨酸酶缺乏症的阿米什儿童的 PEPD 无义突变。
DOI：
10.1002/ajmg.a.31134
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Scofield,RHal
中科院分区：
文献类型：
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作者：
Wang,Heng;Kurien,BijiT;Lundgren,David;Patel,NishaC;Kaufman,KM;Miller,DavidL;Porter,AndrewC;D'Souza,Anil;Nye,Leah;Tumbush,John;Hupertz,Vera;Kerr,DouglasS;Kurono,S;Matsumoto,H;Scofield,RHal
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 thePEPDgene mutation. © 2006 Wiley‐Liss, Inc.
