ClinVar

In 2 unrelated patients with juvenile-onset neuronal ceroid lipofuscinosis-2 (CLN2; 204500), Sleat et al. (1999) identified a rare monoallelic mutation that resulted in an arg447-to-his (R447H) substitution in the CLN2 gene. Both of these patients were compound heterozygous, with either a monoallelic common splice junction mutation (607998.0004) or the arg208-to-ter mutation (R208X; 607998.0003). Both patients were originally diagnosed with juvenile-onset CLN3 (204200) on the basis of age at onset, age at death, and inclusion morphology. Sleat et al. (1999) considered it likely that the R447H mutation caused incomplete loss of function of the CLN2 protease, resulting in the protracted phenotype. The findings indicated that an attenuated form of CLN2 (i.e., with juvenile onset) may not be correctly diagnosed or may be confused with other later-onset neurodegenerative disorders. Such observations are not uncommon with other lysosomal storage diseases, in which missense mutations result in a partial dysfunction and subsequent mild or protracted phenotype. The possible phenotype of an individual homozygous for the R447H allele remained unknown.