Background Huntington’s disease (HD) is caused by an unstable expanded trinucleotide (CAG) repeat in the huntingtin (HTT) gene. Presentation involves a clinical triad of symptoms: behavioural problems, movement disorder and cognitive decline. Elsewhere, between 1 and 7% of individuals diagnosed do not carry the mutation and are said to have an HD phenocopy; a term used to describe any syndrome that manifests HD-like symptoms in the absence of an HTT expansion.

In South Africa, direct mutation testing is performed in the public sector by the National Health Laboratory Service. Approximately 30% of patients referred for confirmation of an HD diagnosis do not carry an HTT expansion. Huntington’s disease-like 2 (HDL2) has recently been incorporated into routine diagnostic testing for HD referrals as up to one third of patients negative for the HTT expansion were found to carry an expansion in the underlying junctophilin-3 (JPH3) gene.

Aim To investigate the occurrence of mutations associated with HD phenocopies in a cohort of black South African individuals.

Methods Records revealed 105 individuals with negative results for the HTT and JPH3 expansions. Molecular screening was performed for: Spinocerebellar ataxia (SCA) subtypes: 1, 2, 7, 17; Dentatorubral-palidolluysian atrophy (DRPLA) and C9orf72 hexanucleotide expansions.

Results Thus far a single expansion has been identified confirming SCA2 and results are pending for the C9orf72 screen.

Conclusions Mutations associated with HD phenocopies appear to be absent in this cohort and may indicate the presence of novel genes and/mutations causing the HD-like phenotype.