title: A novel homozygous GALC mutation: very early onset and rapidly progressive Krabbe disease.
abstract: A clear cut genotype-phenotype correlation for Krabbe disease is not available. Therefore, it is important to identify new mutations and their associated phenotypes to predict the prognosis of the disease. The aim of this study is to identify the causative mutation(s) in a family with Krabbe disease. After a clinical evaluation and suspicion of Krabbe disease galactocerebrosidase activity was analyzed and GALC gene mutation analysis was performed. The galactocerebrosidase enzyme activity was 0.01 nmol/mg/h protein (normal range 0.8-4). For further investigation mutation screening was performed by Sanger sequencing across the 17 exons of GALC gene. A novel homozygous mutation c.727delT (p.S243QfsX7) was found. In this study we present the clinical findings along with a novel GALC mutation in a consanguineous Turkish family. Although the relationship between the various genotypes and phenotypes in Krabbe disease has not been fully elucidated an accurate genetic family study is helpful for genetic counseling follow-up and therapy of Krabbe disease. Also, it is important to identify new mutations in order to clarify their clinical importance, to assess the prognosis of the disease, and to suggest either prenatal diagnosis or preimplantation genetic diagnosis to the effected families.
authors.affiliation: Department of Pediatric Nutrition and Metabolism, Erciyes University School of Medicine, Kayseri 38039, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Kardas
authors.forename: Asli Subasioglu
authors.initials: AS
authors.lastname: Uzak
authors.forename: Mohammad Arif
authors.initials: MA
authors.lastname: Hossain
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
authors.forename: Mehmet
authors.initials: M
authors.lastname: Canpolat
authors.forename: Ali
authors.initials: A
authors.lastname: Yıkılmaz
mesh_terms: D017668:Age of Onset; D018450:Disease Progression; D005698:Galactosylceramidase / Q000235:genetics*; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D007223:Infant; D007965:Leukodystrophy, Globoid Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D014421:Turkey
chemical_list: D005698:Galactosylceramidase