Cln3

Cln3, also known as CLN3, is a gene that encodes a lysosomal membrane protein commonly referred to as battenin. The CLN3 gene is located on chromosome 16 in humans and is expressed in many tissues, with higher levels in the brain. The precise function of battenin is not fully understood, but it is believed to participate in lysosomal homeostasis, endosomal-lysosomal trafficking, and possibly autophagy. Mutations in CLN3 cause Batten disease, specifically the juvenile form of neuronal ceroid lipofuscinosis (JNCL).

Inheritance of CLN3-related disease is autosomal recessive. Individuals with two mutated copies develop the disorder, while carriers have one mutated copy and typically do not show the full disease phenotype. Although CLN3 mutations are rare, they are a major cause of juvenile NCL in many populations.

Clinical presentation usually begins in childhood, commonly between ages 4 and 7. Early signs include progressive vision loss due to retinal degeneration, followed by seizures, cognitive decline, and motor deterioration. Neurodegeneration leads to ataxia, behavioral changes, and loss of independent ambulation. A hallmark feature is the accumulation of lipofuscin-like storage material in neurons and other cell types, reflected in tissue analyses.

Diagnosis is based on clinical features supported by imaging and laboratory tests. Brain MRI often shows cerebral and cerebellar atrophy; EEG may reveal epileptiform activity. Definitive diagnosis is established by genetic testing identifying pathogenic CLN3 variants, with supporting histopathology showing autofluorescent ceroid-lipofuscin in tissues.

Management is supportive and multidisciplinary, addressing vision, seizures, motor decline, and life planning. There is no approved disease-modifying therapy for CLN3-related Batten disease; research into gene therapy and other approaches is ongoing. Prognosis is variable but generally involves progressive neurological deterioration, with survival typically into adolescence or early adulthood.