Genetic and functional studies reveal a novel noncoding variant in GALT associated with a false positive newborn screening result for galactosemia.
Genetic and functional studies reveal a novel noncoding variant in GALT associated with a false positive newborn screening result for galactosemia.
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遗传和功能研究揭示了 GALT 中的一种新型非编码变异与新生儿半乳糖血症筛查结果假阳性相关。
DOI：
10.1016/j.cca.2015.04.030
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Fridovich-Keil,JudithL
中科院分区：
文献类型：
--
作者：
Liu,Ying;Sidhu,Alpa;Bean,LoraH;Conway,RobertL;Fridovich-Keil,JudithL
BackgroundClassic galactosemia (CG) is a potentially lethal genetic disorder that results from profound loss of galactose-1-phosphate uridylyltransferase (GALT). CG is detected by newborn screening (NBS) in many countries; however, conclusive diagnosis can be complex due to broad and overlapping ranges of GALT activity. Molecular studies can also be complex due to allelic heterogeneity at theGALTlocus.MethodsWe conducted both biochemical and molecular follow-up studies for an infant flagged by NBS for possible galactosemia. To clarify the diagnosis we also conducted biochemical and RNA studies of lymphoblasts prepared from the child and one parent.ResultsWe identified a novel noncodingGALTvariant, c.377+17C>T, that was homozygous in the child and heterozygous in both parents. The child and both parents also showed diminished GALT activity in red blood cells, and transformed lymphoblasts from the child and one parent further showed diminished GALT activity. However, qRT-PCR studies demonstrated apparently normalGALTmRNA levels in lymphoblasts, and Gal-1P values measured in the child following galactose exposure in infancy and at 1 year were normal.ConclusionsThese results highlight the existence of rare but apparently benign variants inGALTand underscore the need for functional studies to distinguish pathogenic from benign variants.
