对来自印度的五名患有泰-萨克斯病儿童的己糖胺酶A基因缺失-重复的鉴定。
Identification of deletion-duplication in HEXA gene in five children with Tay-Sachs disease from India.
作者信息
Sheth Jayesh, Mistri Mehul, Mahadevan Lakshmi, Mehta Sanjeev, Solanki Dhaval, Kamate Mahesh, Sheth Frenny
机构信息
Biochemical and Molecular Genetics, FRIGE's Institute of Human Genetics, FRIGE House, Satellite, Ahmedabad, Gujarat, 380 015, India.
Medgenome Labs Pvt Ltd, Bangalore, India.
出版信息
BMC Med Genet. 2018 Jul 4;19(1):109. doi: 10.1186/s12881-018-0632-7.
BACKGROUND
Tay-Sachs disease (TSD) is a sphingolipid storage disorder caused by mutations in the HEXA gene. To date, nearly 170 mutations of HEXA have been described, including only one 7.6 kb large deletion.
METHODS
Multiplex Ligation-dependent Probe Amplification (MLPA) study was carried out in 5 unrelated patients for copy number changes where heterozygous and/or homozygous disease causing mutation/s could not be identified in the coding region by sequencing of HEXA gene.
RESULTS
The study has identified the presence of a homozygous deletion of exon-2 and exon-3 in two patients, two patient showed compound heterozygosity with exon 1 deletion combined with missense mutation p.E462V and one patient was identified with duplication of exon-1 with novel variants c.1527-2A > T as a second allele.
CONCLUSION
This is the first report of deletion/duplication in HEXA gene providing a new insight into the molecular basis of TSD and use of MLPA assay for detecting large copy number changes in the HEXA gene.
背景
泰-萨克斯病（TSD）是一种由HEXA基因突变引起的鞘脂贮积症。迄今为止，已描述了近170种HEXA突变，其中仅一种7.6 kb的大片段缺失。
方法
对5例无亲缘关系的患者进行多重连接依赖探针扩增（MLPA）研究，以检测拷贝数变化，这些患者通过HEXA基因测序在编码区未鉴定出杂合和/或纯合致病突变。
结果
该研究在两名患者中鉴定出存在外显子2和外显子3的纯合缺失，两名患者表现为外显子1缺失与错义突变p.E462V的复合杂合性，一名患者被鉴定为外显子1重复，第二个等位基因为新变异c.1527-2A>T。
结论
这是关于HEXA基因缺失/重复的首次报道，为TSD的分子基础以及使用MLPA检测HEXA基因的大片段拷贝数变化提供了新的见解。
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