VARIANT LATE INFANTILE NEURONAL CEROID LIPOFUSCINOSIS – A NOVEL C>G MISSENSE MUTATION AT THE CLN8 GENE – THE FIRST CASE OUTSIDE FINLAND OR TURKEY

Objectives: The clinical picture of the neuronal ceroid lipofiscinoses (NCL) is diverse and in addition to the main categories there are many variants that are determined by the clinical picture, ultra-structural morphology and genetic analysis. To further delineate the phenotypic and mutational spectrum of NCL we investigated a patient with an atypical form of NCL, whose clinical picture could fit a variant form of late infantile NCL.

Methods: Our investigation included clinical evaluation, electron microscopy examination and a molecular genetic study of skin fibroblasts. This study included linkage analysis to check for the main variants of the NCL spectrum, haplotype analysis with markers 140CA, 159CA and D8S264 and gene sequencing.

Results: The clinical picture of the patient (a 10 year old male of Palestinian origin) was characterized by progressive visual loss, ataxia, mental decline, and myoclonic seizures with onset at 5.3 years of age and rapid deterioration. Ultrastructural analysis of skin cells revealed cellular curvilinear structures, granular osmophilic bodies and fingerprint stacks. Linkage analysis ruled out CLN6 but was positive for CLN8. Sequencing of exons 2 and 3 of the CLN8 gene revealed a C>G missense mutation at a conserved amino acid glutamine 256 to glutamic acid.

Conclusion: The above findings indicate that in addition to clustering of CLN8 in Finland (northern epilepsy) and Turkey (a subset of variant late infantile NCL) variant, late infantile NCL allelic to CLN8 occurs in other Middle-Eastern countries.