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Neuronal Ceroid Lipofuscinoses Type 1, Genetic Testing

Neuronal Ceroid Lipofuscinoses (NCLs), or Batten disease, represent a group of rare inherited neurodegenerative disorders primarily affecting the nervous system. Several subtypes of NCLs are associated with mutations in different genes. NCL type 1, also known as CLN1 disease or infantile NCL, is caused by mutations in the PPT1 gene.

Neuronal ceroid lipofuscinoses genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).

Critical features of Neuronal Ceroid-Lipofuscinoses type 1 (CLN1 disease) include:

  • Onset in Infancy: CLN1 disease typically manifests in infancy, often between 6 months and 2 years of age.
  • Motor and Cognitive Decline: Affected individuals experience a progressive decline in motor skills and cognitive abilities. Developmental milestones are often lost.
  • Seizures: Seizures are a common feature of CLN1 disease and may be one of the earliest signs.
  • Visual Impairment: Visual impairment, including blindness, is a characteristic feature. Vision loss is often severe.
  • Hypotonia: Hypotonia, or low muscle tone, is observed, contributing to difficulties with movement and coordination.
  • Speech and Language Regression: Loss of speech and language skills is ordinary as the disease progresses.
  • Myoclonic Jerks: Jerky, involuntary movements (myoclonic jerks) may occur.
  • Brain Atrophy: Progressive brain atrophy is evident in imaging studies.
  • Loss of Motor Function: As the disease advances, individuals with CLN1 disease may lose the ability to walk and become wheelchair-bound.
  • Shortened Lifespan: Unfortunately, CLN1 disease is associated with a significantly shortened lifespan, often leading to death in childhood or adolescence.

CLN1 disease is inherited in an autosomal recessive manner, meaning that affected individuals inherit a mutated PPT1 gene from both parents. The PPT1 gene provides instructions for making the enzyme palmitoyl-protein thioesterase 1, which breaks specific proteins in the lysosomes.

There is currently no cure for CLN1 disease, and treatment is primarily supportive, focusing on managing symptoms and improving the quality of life. Seizures may be treated with antiepileptic medications, and supportive therapies such as physical and occupational therapy can help manage motor difficulties.

Genetic counseling is essential for families affected by CLN1 disease to understand the inheritance pattern, assess the risk of having affected children, and explore reproductive options. Due to the severity of the condition, early diagnosis is crucial for providing supportive care and addressing specific needs.

More Information

PPT1-associated NCL, or ceroid lipofuscinosis type 1, is an autosomal recessive lysosomal storage disease characterized by the ubiquitous accumulation of ceroid-lipofuscin lipopigmentation material. It is caused by pathogenic variants in the PPT1 gene encoding for palmitoyl protein thioesterase 1, a lysosomal enzyme.

The c.451C>T (p.Arg151Ter) variant is globally the most frequent variant in the PPT1 gene and produces an afunctional truncated protein. It has been observed both in the homozygous state, in patients with severe symptoms, and the compound heterozygous state.

The c.223A>C (p.Thr75Pro) substitution in the PPT1 gene is a relatively common pathogenic variant that has been detected in multiple individuals with juvenile neuronal ceroid lipofuscinosis in compound heterozygosity with a second mutation. This variant accounts for 13% of alleles detected in the US and Canada and is associated with late disease onset.

The c.364A>T (p.Arg122Trp) variant in the PPT1 gene is the predominant variant in patients in the Finnish population and has also been observed in other populations. This variant significantly affects the enzyme's activity.

Neuronal ceroid lipofuscinoses type 1 genetic testing analyzes the 11 most frequent pathogenic mutations of the PPT1 gene.

The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).

Additional information
Results Time4 - 5 Weeks
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