PNKP Mutations Identified by Whole-Exome Sequencing in a Norwegian Patient with Sporadic Ataxia and Edema

Cerebellum. 2017 Feb;16(1):272-275. doi: 10.1007/s12311-016-0784-y.

Abstract

We identified PNKP mutations in a Norwegian woman with AOA. This patient had the typical findings with cognitive dysfunction, peripheral neuropathy, cerebellar dysarthria, horizontal nystagmus, oculomotor apraxia, and severe truncal and appendicular ataxia. In addition, she had hypoalbuminemia and massive lower limb edema which showed some improvement with treatment. Exome sequencing identified two heterozygous mutations, one in exon 14 (c.1196T>C, p.Leu399Pro) and one in exon 16 (c.1393_1396del, p.Glu465*). This is the first non-Portuguese patient with AOA due to PNKP mutations and provides independent verification that PNKP mutations cause AOA.

Keywords: AOA4; Ataxia; Edema; Hypoalbuminemia; Oculomotor apraxia.

Publication types

  • Case Reports

MeSH terms

  • Apraxias / congenital*
  • Apraxias / diagnostic imaging
  • Apraxias / genetics
  • Apraxias / pathology
  • Ataxia / diagnostic imaging
  • Ataxia / genetics*
  • Ataxia / pathology
  • Cogan Syndrome / diagnostic imaging
  • Cogan Syndrome / genetics*
  • Cogan Syndrome / pathology
  • DNA Repair Enzymes / genetics*
  • Edema / genetics*
  • Edema / pathology
  • Female
  • Humans
  • Leg / pathology
  • Middle Aged
  • Mutation*
  • Norway
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • White People / genetics

Substances

  • PNKP protein, human
  • Phosphotransferases (Alcohol Group Acceptor)
  • DNA Repair Enzymes

Supplementary concepts

  • Apraxia, oculomotor, Cogan type