Array CGH improves detection of mutations in the GALC gene associated with Krabbe disease

Orphanet Journal of Rare Diseases

Madhuri Hegde²  Patricia K Duffner¹  Ephrem L H Chin²  Alice K Tanner² 

[1]Hunter James Kelly Research Institute, Department of Neurology, School of Medicine, State University of New York at Buffalo, Buffalo, NY, USA

[2]Emory Genetics Laboratory, Department of Human Genetics, Emory University, Atlanta, GA, USA

关键词: Array CGH;    Duplication;    Deletion;    GALC;    Krabbe disease;   

Others  :  864353
DOI  :  10.1186/1750-1172-7-38

 received in 2012-01-17, accepted in 2012-06-15,  发布年份 2012

【 摘 要 】

Background

Krabbe disease is an autosomal recessive lysosomal storage disorder caused by mutations in the GALC gene. The most common mutation in the Caucasian population is a 30-kb deletion of exons 11 through 17. There are few other reports of intragenic GALC deletions or duplications, due in part to difficulties detecting them.

Methods and results

We used gene-targeted array comparative genomic hybridization (CGH) to analyze the GALC gene in individuals with Krabbe disease in whom sequence analysis with 30-kb deletion analysis identified only one mutation. In our sample of 33 cases, traditional approaches failed to identify two pathogenic mutations in five (15.2%) individuals with confirmed Krabbe disease. The addition of array CGH deletion/duplication analysis to the genetic testing strategy led to the identification of a second pathogenic mutation in three (9.1%) of these five individuals. In all three cases, the deletion or duplication identified through array CGH was a novel GALC mutation, including the only reported duplication in the GALC gene, which would have been missed by traditional testing methodologies. We report these three cases in detail. The second mutation remains unknown in the remaining two individuals (6.1%), despite our full battery of testing.

Conclusions

Analysis of the GALC gene using array CGH deletion/duplication testing increased the two-mutation detection rate from 84.8% to 93.9% in affected individuals. Better mutation detection rates are important for improving molecular diagnosis of Krabbe disease, as well as for providing prenatal and carrier testing in family members.

【 授权许可】

   
2012 Tanner et al.; licensee BioMed Central Ltd.

【 图 表 】

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