A Broad Spectrum of Developmental Delay in a Large Cohort of Prolidase Deficiency Patients Demonstrates Marked Interfamilial and Intrafamilial Phenotypic Variability
A Broad Spectrum of Developmental Delay in a Large Cohort of Prolidase Deficiency Patients Demonstrates Marked Interfamilial and Intrafamilial Phenotypic Variability
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DOI：
10.1002/ajmg.b.30945
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发表时间：
2010-01-01
影响因子：
2.8
通讯作者：
Mandel, Hanna
中科院分区：
文献类型：
--
作者：
Falik-Zaccai, Tzipora C.;Khayat, Morad;Mandel, Hanna
脯氨酸酶缺乏症（PD）是一种罕见的、泛民族的常染色体隐性遗传病，具有广泛的表型谱。在世界范围内，已经报道了17种PEPD基因的致病突变。本研究的目的是对居住在以色列北部的10种阿拉伯穆斯林和德鲁兹血统的20例增殖酶缺陷患者进行临床和分子特征分析。1例PD患者表现为发育迟缓和面部畸形。典型的PD皮肤症状，脾肿大，不同程度的反复呼吸道感染。2例患者为系统性红斑狼疮（SLE）， 1例为新型囊性纤维化表型。直接DNA测序发现了两个新的错义突变，A212P和L368R。此外，先前报道的S202F突变在来自7个德鲁兹族和3个阿拉伯穆斯林族的17名患者中被检测到。S202F纯合突变的患者表现出相当大的家族间和家族内表型变异性。这种突变在居住在以色列北部的阿拉伯穆斯林和德鲁兹人中非常普遍，并且在患者及其父母中存在相同的单倍型，沿500,000 bp，这表明在德鲁兹人从主流穆斯林社会分离之前发生了一个创始事件。(C) 2009 Wiley-Liss, Inc。
Prolidase deficiency (PD) is a rare, pan-ethnic, autosomal recessive disease with a broad phenotypic spectrum. Seventeen causative mutations in the PEPD gene have been reported worldwide. The purpose of this study is to characterize, clinically and molecularly, 20 prolidase deficient patients of Arab Moslem and Druze origin from 10 kindreds residing in northern Israel. An PD patients manifested developmental delay and facial dysmorphism. Typical PD dermatological symptoms, splenomegaly, and recurrent respiratory infections presented in varying degrees. Two patients had systemic lupus erythematosus (SLE), and one a novel cystic fibrosis phenotype. Direct DNA sequencing revealed two novel missense mutations, A212P and L368R. In addition, a previously reported S202F mutation was detected in 17 patients from seven Druze and three Arab Moslem kindreds. Patients homozygous for the S202F mutation manifest considerable interfamilial and intrafamilial phenotypic variability. The high prevalence of this mutation among Arab Moslems and Druze residing in northern Israel, and the presence of an identical haplotype along 500,000 bp in patients and their parents, suggests a founder event tracing back to before the breakaway of the Druze from mainstream Moslem society. (C) 2009 Wiley-Liss, Inc.