A novel PCFT gene mutation (p.Cys66LeufsX99) causing hereditary folate malabsorption
A novel PCFT gene mutation (p.Cys66LeufsX99) causing hereditary folate malabsorption
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DOI：
10.1016/j.ymgme.2009.11.004
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发表时间：
2010-03-01
影响因子：
3.8
通讯作者：
Maher, Eamonn R.
中科院分区：
文献类型：
--
作者：
Meyer, Esther;Kurian, Manju A.;Maher, Eamonn R.
遗传性叶酸吸收不良（HFM）是一种罕见的常染色体隐性遗传疾病，其特征是肠道叶酸吸收障碍和叶酸转运到中枢神经系统受损。先前仅在10名患有这种疾病的个体中报道了肠叶酸转运蛋白PCFT的突变。本研究的目的是描述一个有四个受影响个体的家族中这种疾病的临床表型并确定其分子基础。一个巴基斯坦血统的常染色体隐性遗传HFM的近亲家庭被确定和临床表型。遗传连锁研究后，所有编码外显子的PCFT基因进行了筛选突变的直接测序。四个受影响的患者的临床表型进行了描述。PCFT的直接测序揭示了一个新的纯合移码突变（c.194dupG）在一个单核苷酸重复在外显子I预测导致截短的蛋白质（p.Cys66LeufsX99）。本报告扩展了目前对HFM表型表现和PCFT突变谱的认识。(C)2009 Elsevier Inc. All rights reserved.
Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder which is characterized by impaired intestinal folate malabsorption and impaired folate transport into the central nervous system. Mutations in the intestinal folate transporter PCFT have been reported previously in only 10 individuals with this disorder. The purpose of the current Study was to describe the clinical phenotype and determine the molecular basis for this disorder in a family with four affected individuals. A consanguineous family of Pakistani origin with autosomal recessive HFM was ascertained and clinically phenotyped. After genetic linkage studies all coding exons of the PCFT gene were screened for mutations by direct sequencing.The clinical phenotype of four affected patients is described. Direct sequencing of PCFT revealed a novel homozygous frameshift mutation (c.194dupG) at a mononucleotide repeat in exon I predicted to result in a truncated protein (p.Cys66LeufsX99). This report extends current knowledge on the phenotypic manifestations of HFM and the PCFT mutation spectrum. (C) 2009 Elsevier Inc. All rights reserved.