ClinVar

Sleat et al. (1997) described compound heterozygosity in 2 sibs with late-infantile onset of neuronal ceroid lipofuscinosis-2 (CLN2; 204500). One allele of the CLN2 gene carried the R208X nonsense mutation (607998.0003); the other allele showed a splice site mutation, a G-to-C transversion of the consensus AG 3-prime splice acceptor site immediately preceding 523T of the cDNA sequence.

In affected members of a Dutch family with autosomal recessive spinocerebellar ataxia-7 (SCAR7; 609270), originally reported by Breedveld et al. (2004), Sun et al. (2013) identified compound heterozygous mutations in the TPP1 gene: a G-to-C transversion in intron 5 (c.509-1G-C) resulting in a frameshift and premature termination (Val170GlyfsTer29), and V466G (607998.0010). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. An unrelated Dutch woman with the disorder was also found to be compound heterozygous for these 2 mutations, although a founder effect could not be confirmed. Residual TPP1 activity in patient lymphocytes was 10 to 15% that of controls, with 5% activity in patient fibroblasts.

In an 11-year-old girl with SCAR7, Dy et al. (2015) identified compound heterozygous mutations in the TPP1 gene: c.509-1G-C, and a missense mutation (E343D; 607998.0011).