A novel deletion creating a new terminal exon of the dihydrolipoyl transacylase gene is a founder mutation of Filipino maple syrup urine disease
A novel deletion creating a new terminal exon of the dihydrolipoyl transacylase gene is a founder mutation of Filipino maple syrup urine disease
复制标题
DOI：
10.1016/j.ymgme.2003.10.006
复制
发表时间：
2004-02-01
影响因子：
3.8
通讯作者：
Matsuo, M
中科院分区：
文献类型：
--
作者：
Silao, CLT;Padilla, CD;Matsuo, M
枫糖尿病（MSUD）是一种罕见的常染色体隐性支链氨基酸代谢疾病。在菲律宾，许多MSUD病例已被临床诊断。在这里，对来自菲律宾的13个不相关家庭的二氢硫酰基转酰基酶（E2）基因进行了分子分析。在13个家族中，有8个家族发现了10号内含子L1重复序列和11号外显子Alu重复序列之间的非同源重组导致的10号内含子4.1 kb和11号外显子601 bp的新缺失，其中5个家族为纯合突变，表明该突变是菲律宾MSUD的一个始发突变。由此产生的突变E2 mRNA在外显子10后含有239 bp的插入，从而产生一个新的终端外显子。对该缺失进行的大规模人群筛选显示，在100名正常菲律宾人中发现了一名突变携带者。这些发现表明，有限数量的突变可能是菲律宾人群中MSUD的基础，可能有助于该人群中MSUD的产前诊断和携带者检测。(C) 2003 Elsevier Inc.版权所有。
Maple syrup urine disease (MSUD) is a rare, autosomal-recessive disorder of branched-chain amino-acid metabolism. In the Philippines, many MSUD cases have been diagnosed clinically. Here, molecular analysis of the dihydrolipoyl transacylase (E2) gene was done in 13 unrelated families from the Philippines. A novel deletion spanning 4.1 kb of intron 10 and 601 bp of exon 11, caused by non-homologous recombination between an L1 repeat in intron 10 and an Alu repeat in exon 11, was found in 8 out of 13 families, with 5 of them being homozygous for the mutation, implicating it as a founder mutation of Filipino MSUD. The resulting mutant E2 mRNA contains a 239-bp insertion after exon 10, thereby producing a new terminal exon. Large-scale population screening of the deletion revealed that one carrier of the mutation was identified in 100 normal Filipinos. These findings suggest that a limited number of mutations might underlie MSUD in the Filipino population, potentially facilitating prenatal diagnosis and carrier detection of MSUD in this group. (C) 2003 Elsevier Inc. All rights reserved.