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Neuronal Ceroid Lipofuscinoses Type 5, Genetic Testing

Neuronal Ceroid Lipofuscinoses type 5 (NCL5), also known as CLN5 disease, is a rare neurodegenerative disorder that falls under the category of Batten disease, a group of inherited conditions characterized by the accumulation of lipopigments in the cells of the nervous system. Mutations in the CLN5 gene cause CLN5 disease.

Neuronal ceroid lipofuscinoses type 5 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 5 (CLN5 disease) include:

  • Onset: CLN5 disease typically begins in childhood, often between the ages of 4 and 7.
  • Seizures: Seizures are a common feature of CLN5 disease and may be one of the initial symptoms.
  • Cognitive Decline: Progressive decline in cognitive abilities occurs, leading to intellectual disability.
  • Motor Dysfunction: Individuals with CLN5 disease may experience a gradual decline in motor skills, including coordination and balance.
  • Visual Impairment: Vision loss is a characteristic feature, and affected individuals may experience difficulty with visual tasks.
  • Speech and Language Regression: Speech and language skills loss may occur over time.
  • Behavioral Changes: Changes in behavior, including irritability and aggression, may be observed.
  • Movement Abnormalities: Some individuals may develop movement abnormalities such as tremors and myoclonic jerks.
  • Brain Atrophy: Imaging studies may reveal progressive brain atrophy.
  • Autosomal Recessive Inheritance: CLN5 disease follows an autosomal recessive inheritance pattern, meaning that affected individuals inherit mutated CLN5 genes from both parents.

The CLN5 gene provides instructions for making a protein involved in lysosomal function. Lysosomes are cellular structures responsible for breaking down and recycling various substances. Mutations in the CLN5 gene result in impaired lysosomal function, accumulating lipopigments, and subsequent cell damage in the nervous system.

There is currently no cure for CLN5 disease, and management is primarily supportive, focusing on symptom relief and improving the quality of life for affected individuals. Seizures may be treated with antiepileptic medications, and other supportive measures, such as physical and occupational therapy, may be employed.

Genetic counseling is essential for families affected by CLN5 disease to understand the inheritance pattern, assess the risk of having affected children, and discuss available reproductive options. Due to the progressive and debilitating nature of the condition, early diagnosis is crucial for initiating appropriate supportive care and interventions.

More Information

Ceroid lipofuscinosis type 5 is caused by mutations in the CLN5 gene, which encodes for the neuronal ceroid lipofuscinosis 5 protein expressed in most tissues. In the brain, the CLN5 protein is found in neurons and glial cells. At the cellular level, it is localized in the lysosome, and its function is not yet well understood. However, it is thought to play a key role in maintaining lysosomal pH.

Mutations in the CLN5 gene are associated with accumulating storage material in lysosomes. More than 58 different mutations have been described in patients with ceroid lipofuscinosis that can produce the disease in both homozygosis and compound heterozygosis. Among these, the most prominent is the c.1175_1176delAT variant, also known as Y392*, first identified in Finnish patients in the 1990s and may have a high frequency in some regions of Finland. Several variants in CLN5 have been detected distributed throughout different European countries, in the United States, Canada, South America, and Asia.

The c.1175_1176delAT variant causes deletion of two nucleotides and causes a reading frame shift that results in the appearance of an early stop codon. Functional studies suggest that it results in an unstable protein that cannot reach the lysosome.

Neuronal ceroid lipofuscinoses type 5 genetic testing analyzes the 5 most frequent pathogenic mutations of the CLN5 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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