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Download Neuronal Ceroid-Lipofuscinosis type 3 (NCL3)
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Version 5 (October 2012) NE THAMES REGIONAL MOLECULAR GENETICS SERVICE Neuronal Ceroid-Lipofuscinosis type 3 (NCL3) (Juvenile Batten disease (JNCL)) Contact details Molecular Genetics GOSH NHS Trust Level 6 York House 37 Queen Square London WC1N 3BH Telephone +44 (0) 20 7762 6888 Fax +44 (0) 20 7813 8196 Introduction Neuronal ceroid-lipofuscinosis type 3 (NCL3; MIM #204200) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CLN3 gene. NCL3 is one of at least eight genetically distinct diseases associated with the NCL disease spectrum. NCL3 is generally referred to as juvenile NCL (JNCL) due typical onset of symptoms between the ages of 4 and 7 years. A rare variant form of JNCL (vJNCL) has been associated with mutations in the CLN1 gene (usually associated with the infantile form of the disease). NCL3 is typically characterised by normal development until the onset of visual failure due to retinal degeneration between 4 and 7 yrs. Progression of visual loss is usually rapid. Other clinical features include seizures and psychomotor deterioration; prognosis is poor. The differential diagnosis of NCL3 from the other NCL types is based on age of onset, clinical phenotype and ultra structural characterisation of the storage material. NCL3 is characterised by the accumulation of auto fluorescent lipopigment with a fingerprint profile in neurones and other cell types and the presence of vacuolated lymphocytes on a blood smear. The CLN3 gene (16p12) consists of 15 exons spanning 15kb of genomic DNA. A 1.02kb deletion (introns 6-8) is reported to account for ~69% of JNCL alleles (~85% in Finnish population). Other disease causing mutations are family specific and found throughout the gene. Samples required 5ml venous blood in plastic EDTA bottles (>1ml from neonates) Prenatals must be arranged in advance, through a Clinical Genetics department if possible. Amniotic fluid or CV samples should be sent to Cytogenetics for dissecting and culturing, with instructions to forward the sample to the Regional Molecular Genetics laboratory for analysis A completed DNA request card should accompany all samples. Referrals Clinical and histopathological review of the affected patient is recommended to indicate a diagnosis of NCL3. Please supply details of biochemical and histopathological testing undertaken, clinical details and any relevant pedigree. If the necessary patient samples are unavailable genetic testing can be undertaken in the parents of an affected child. Carrier testing can be offered to the adult relatives of NCL3 patients once a disease causing mutation has been identified. Prenatal testing Prenatal testing is available for families in which the diagnosis of NCL3 has been confirmed by mutation analysis. Please contact the laboratory to discuss. Service offered Level 1: Testing for the common 1.02kb deletion. Level 2: Screening of the CLN3 gene by direct sequence analysis. Target reporting time 2 weeks for routine 1.02kb deletion mutation test in the index case. 8 weeks for sequence analysis of the gene in the index case. 2 weeks for family member carrier testing. For urgent samples please contact the laboratory. Contact details for histopathology laboratory: Histopathology, Level 3, Camelia Botnar Laboratories, Great Ormond Street Hospital, London WC1N 3JH. Tel: +44 (0) 20 7405 9200 (x7907) Patient details To facilitate accurate testing and reporting please provide patient demographic details (full name, date of birth, address and ethnic origin), details of any relevant family history and full contact details for the referring clinician