ClinVar

In affected members of 3 Jewish Bukharian families with hereditary sensory and autonomic neuropathy type IX with developmental delay (HSAN9; 615031), who were originally diagnosed with autosomal recessive spastic paraplegia-49 (SPG49), Oz-Levi et al. (2012) identified a homozygous 1-bp deletion (c.3416delT) in exon 16 of the TECPR2 gene, resulting in a frameshift and premature termination (Leu1139ArgfsTer75). The mutation was found by exome sequencing and segregated with the disorder in each family. The mutation was not present in 2,007 non-Bukharian controls, but was found in 4 of 300 Jewish Bukharian control chromosomes, yielding an allele frequency of 0.013 in that ethnic group. In vitro cellular expression assays indicated that the mutant protein was degraded by the proteosome.

In a patient with HSAN9 (patient 3), Heimer et al. (2016) identified compound heterozygosity for 2 mutations in the TECPR2 gene: c.3416delT (c.3416delT, NM_001172631) and a 1-bp deletion (c.1319delT; 615000.0002) in exon 8, predicted to result in a frameshift and premature termination (Leu440ArgfsTer19). The mutations were identified by Sanger sequencing of the TECPR2 gene, and both parents were shown to be mutation carriers.

In 2 patients with HSAN9, Neuser et al. (2021) identified homozygosity for the c.3416delT mutation in the TECPR2 gene. They noted that the minor allele frequency of the c.3416delT variant was 2/247,472 in only heterozygous state in the gnomAD database.