TY  - JOUR
TI  - Clinical and molecular findings in 6 Turkish cases with Krabbe disease
AB  - Background. Krabbe disease is a rare lysosomal storage disorder with a neurodegenerative course that occurs because of the deficiency of the beta-galactocerebrosidase (GALC) enzyme activity. The genetic basis of Krabbe disease consists of biallelic mutations in the GALC gene, but the genetic spectrum in the Turkish population is poorly defined. We aimed to present a Turkish case-series with infantile-onset Krabbe disease, define the clinical and molecular findings and compare the genetic spectrum with the mutations previously reported in the literature. Methods. Six cases, who were referred to our clinic between 2015-2019, with a definite diagnosis of infantileonset Krabbe disease were included in the study. The family history, clinical information, biochemical and radiological examinations of the patients were screened and evaluated. All encoded exons and exon-intron regions of the GALC gene were sequenced using next generation sequencing technology. Multiplex ligationdependent probe amplification analysis was used for deletion type mutations that could not be detected by sequence analysis. Results. GALC gene sequence analysis revealed four known mutations including c.1394C>T (p.Thr465Ile), c.411_413delTAA (p.Lys139del), c.820G>C (p.Glu274Gln), and 30 kilobase deletion mutation among the exons 11-17 (IVS10del30kbp). Moreover, the c.1623G>A (p.Trp541Ter) variant, which was not previously reported in the literature, was detected in two cases. Conclusions. We believe that the demonstration of the genetic spectrum of infantile-onset Krabbe disease in Turkish patients will be an important contribution to the GALC mutation data in our country. More importantly, two novel variants were defined. This knowledge may enable early detection and treatment with the advent of a carrier or newborn screening tests.
AU  - sengenc, esma
AU  - Demiral, Emine
AU  - Kolemen, Ayse Betul
AU  - ALKAN, ALPAY
AU  - işcan, akın
AU  - Aslanger, Ayca
AU  - Yeşil, Gözde
DO  - 10.24953/turkjped.2020.3713
PY  - 2022
JO  - Turkish Journal of Pediatrics
VL  - 64
IS  - 1
SN  - 0041-4301
SP  - 69
EP  - 78
DB  - TRDizin
UR  - http://search/yayin/detay/1138114
ER  -