Two Cases of PNPLA6‑Associated Ataxia with Novel Mutations

Evgenii P Nuzhnyi, Ekaterina Y Fedotova, Natalya Y Abramycheva, Zoya V Surnina, Anna S Vetchinova, Maksim N Andreev, Sergei N Illarioshkin

Neurology India ():10.4103/neuroindia.NI_190_20, June 18, 2025. | DOI: 10.4103/neuroindia.NI_190_20

Autosomal recessive cerebellar ataxias (ARCA) are a highly heterogeneous group of hereditary disorders with a wide spectrum of symptoms (peripheral neuropathy, movement disorders, pyramidal tract dysfunction, cognitive impairment, epilepsy, etc.). Most ARCAs represent very rare disorders, such as ataxias with hypogonadotropic hypogonadism (HH).

Application of the next-generation sequencing (NGS) allows the confirmation of heterogeneity of this group of disorders and the identification of several responsible genes, including PNPLA6. Mutations in this gene may lead to a wide spectrum of phenotypes, including Boucher–Neuhäuser syndrome (BNS, MIM 215470) and Gordon Holmes syndrome (GHS). The number of described cases of these diseases worldwide is poor: about 55 patients with BNS (cerebellar ataxia, retinopathy, and HH) and about 10 cases of GHS because of PNPLA6 mutations (cerebellar ataxia, HH, and pyramidal signs). We did not find any reports of these syndromes in Russian or Slavic patients.

Here, we present two cases of BNS and GHS. Four novel mutations in the PNPLA6 gene were detected using targeted NGS panel (Illumina MiSeq).