A novel homozygous GALC variant has been associated with Krabbe disease in a consanguineous family

Neurological Sciences - Tập 39 - Trang 2123-2128 - 2018
Feyza Nur Tuncer1, Sibel Aylin Ugur Iseri1, Zuhal Yapici2, Mahmut Demir3, Meryem Karaca4, Mustafa Calik5
1Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Fatih/Istanbul, Turkey
2Division of Child Neurology, Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
3Department of Pediatrics, Harran University Faculty of Medicine, Sanliurfa, Turkey
4Pediatric Metabolism Disorder Department, Harran University Faculty of Medicine, Sanliurfa, Turkey
5Department of Pediatric Neurology, Harran University Faculty of Medicine, Sanliurfa, Turkey

Tóm tắt

Krabbe disease (KD) or globoid cell leukodystrophy is an autosomal recessive lysosomal storage disorder involving the white matter of the peripheral and the central nervous systems. It is caused by a deficiency of galactocerebrosidase enzyme activity. The most common manifestation is the classical early onset KD that leads to patient’s loss before the age of 2. Herein, we report the evaluation of a consanguineous family with three affected children manifesting severe neurological findings that ended with death before the age of 2, in an attempt to provide genetic diagnosis to the family. One of the children underwent detailed physical and neurological examinations, including brain magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) evaluations. GALC genetic testing on this child enabled identification of a novel homozygous variant (NM_000153.3: c.1394C>T; p.(Thr465Ile)), which confirmed diagnosis as KD. Familial segregation of this variant was performed by PCR amplification and Sanger sequencing that revealed the parents as heterozygous carriers. We believe this novel GALC variant will not only help in genetic counseling to this family but will also aid in identification of future KD cases.

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Neurological Sciences

Tập 39

2123-2128

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