Neuronal ceroid-lipofuscinosis type 1 (NCL1; MIM #256730) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the PPT1 gene which encodes the enzyme palmitoyl�protein thioesterase-1 (PPT1; MIM 600722). NCL1 is one of at least eight genetically distinct diseases associated with the NCL disease spectrum. Onset is typically infantile (INCL) however juvenile and adult (1) onset cases have also been described. The differential diagnosis of NCL1 from other NCL types is based on age of onset, clinical phenotype, ultra structural characterisation of the storage material and PPT1 enzyme activity. NCL1 is characterised by the accumulation of auto fluorescent lipopigment in granular osmiophilic deposits (GROD) in neurones and other cell types using electron microscopy and loss of palmitoyl protein thioesterase-1 (PPT1) enzyme activity in leucocytes and fibroblasts. Typical clinical features of INCL are retarded head growth from about 5 months, hyper excitability (including sleep problems), muscular hypotonia and reduced development of fine motor skills between 10-18 months of age. INCL usually progresses with visual loss (by 18 months - 2 yrs), loss of motor skills, and premature death between 8-13 yrs.
Also known as
Infantile Batten disease, Santavuori disease, Santavuori-Haltia disease, CLN1, Batten
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Clinically affected patients should, wherever possible, have their diagnosis confirmed by analysis of PPT1 enzyme activity in leucocytes and fibroblasts. This should be arranged locally or with the Enzyme Unit at Great Ormond Street Hospital. Such patients may then be referred for mutation analysis. If the necessary patient samples are unavailable genetic testing can be undertaken in the parents of a child. The PPT1 gene (1p32) consists of 9 exons and mutations have been found throughout the gene. The four most common PPT1 mutations are p.Arg122Trp (Finnish-specific), p.Arg151X, p.Thr75Pro and p.Leu10X. The p.Arg151X and p.Leu10X mutations may account for up to 75% of mutations in certain populations. Level 1 Mutation Analysis: Detection of recurrent mutations p.Arg151X, p.Thr75Pro and p.Leu10X by direct sequencing analysis. Level 2 Mutation Analysis: Direct sequencing of all 9 coding exons and intron-exon boundaries.
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Great Ormond Street Hospital NE Thames Regional Genetics Service Laboratories
Great Ormond Street Hospital for Children
37 Queen Square
1ml EDTA neonates, 5ml EDTA adults
Common mutations - 20 days; gene screen - 40 days
Disease / group
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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