A De Novo Variant in Galactose-1-P Uridylyltransferase (GALT) Leading to Classic Galactosemia.
A De Novo Variant in Galactose-1-P Uridylyltransferase (GALT) Leading to Classic Galactosemia.
复制标题
半乳糖-1-P 尿苷酰转移酶 (GALT) 的新变体导致经典半乳糖血症。
DOI：
10.1007/8904_2014_349
复制
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：
Tran,Thanh-ThanhClaireV;Liu,Ying;Zwick,MichaelE;Ramachandran,Dhanya;Cutler,DavidJ;Huang,Xiaoping;Berry,GerardT;Fridovich-Keil,JudithL
Classic galactosemia (CG) is a potentially lethal genetic disease that results from profound impairment of galactose-1-P uridylyltransferase (GALT), the middle enzyme in the Leloir pathway of galactose metabolism. Patients with CG carry pathogenic loss-of-function mutations in both of theirGALTalleles; the parents of patients are considered obligate carriers. We report here a first exception to that rule – ade novoGALTvariant in a patient with classic galactosemia. The new variant, c.563A>C (p.Q188P), which introduces a missense substitution near the active site of the GALT enzyme, was found in the compound heterozygous state in a child with classic galactosemia, but not in either of her parents. Extensive genomic studies of DNA from the child and both parents confirmed the expected degrees of relationship in the trio as well as inheritance of a common c.563A>G (p.Q188R)GALTmutation from the mother. This result demonstrates that not all pathogenicGALTmutations are inherited and raises concern thatGALTmay have a higher new mutation rate than previously believed.
