Clinical and molecular analysis of six novel GALC mutations identified in 7 Chinese children with Krabbe disease

Publication date: Available online 25 May 2017
Source:Brain and Development
Author(s): Lifang Dai, Tongli Han, Xinying Yang, Xu Wang, Jiuwei Li, Junlan Lu, Wuchang Zhang, Xiaotun Ren, Fang Fang
BackgroundKrabbe disease is an autosomal recessive leukodystrophy caused by the deficiency of the galactocerebrosidase (GALC). GALC deficiency results in abnormal accumulation of galactosylsphingosine (psychosine) which cause demyelination of the central and peripheral nervous systems.ObjectiveTo identify clinical manifestation and GALC mutations in Chinese Krabbe disease patients.MethodsWe used targeted next-generation sequencing to identify GALC mutations in Chinese patients with white matter disease.ResultsWe confirmed 7 Chinese patients having GALC gene mutations diagnosed as Krabbe disease, the largest subject number of Chinese patients to date, and found 14 mutations. Of these mutations, six were novel, including four missense mutations (c.1048T>G, c.1585A>C, c.461C>A, c.61G>C), one nonsense mutation (c.129C>G) and one splicing mutation (c.622-1G>A). 58% (4/7) patients had late infantile phenotype. One late infantile patient had a nonsense mutation c.129C>G and a missense mutation c.1048T>G had death at age 3years 5months. Six patients are survive until follow up after 1years 10months to 3years 9months of the disease.ConclusionTargeted next-generation sequencing may help diagnosis atypical symptoms Krabbe disease. Chinese Krabbe disease patients have their own genotype and phenotype.



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