Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene

Caroline Sevin,Sacha Ferdinandusse,Ronald J Wanders,Patrick Aubourg,Hans R Waterham

doi:10.1186/1750-1172-6-8

Caroline Sevin, Sacha Ferdinandusse + Show 3 more

Open Access

https://doi.org/10.1186/1750-1172-6-8

Copy DOI

Abstract

ObjectiveTo expand the spectrum of genetic causes of autosomal recessive cerebellar ataxia (ARCA).Case reportTwo brothers are described who developed progressive cerebellar ataxia at 3 1/2 and 18 years, respectively. After ruling out known common genetic causes of ARCA, analysis of blood peroxisomal markers strongly suggested a peroxisomal biogenesis disorder. Sequencing of candidate PEX genes revealed a homozygous c.865_866insA mutation in the PEX2 gene leading to a frameshift 17 codons upstream of the stop codon. PEX gene mutations usually result in a severe neurological phenotype (Zellweger spectrum disorders).ConclusionsGenetic screening of PEX2 and other PEX genes involved in peroxisomal biogenesis is warranted in children and adults with ARCA.

Highlights

Main causes of autosomal recessive cerebellar ataxia (ARCA) include Friedreich ataxia, ataxia telangiectasia and oculomotor apraxia type 1 and 2 [1,2]
Genetic screening of PEX2 and other PEX genes involved in peroxisomal biogenesis is warranted in children and adults with ARCA
The adult form of X-adrenoleukodystrophy, or adult Refsum disease often develop cerebellar ataxia but have always associated neurological symptoms [5,6]

Summary

Background

Main causes of autosomal recessive cerebellar ataxia (ARCA) include Friedreich ataxia, ataxia telangiectasia and oculomotor apraxia type 1 and 2 [1,2]. On the Wechsler Intelligence Scale for Children (WISC-III), his full, verbal and performance IQ were 75, 84 and 79 He had truncal ataxia, moderate cerebellar tremor, mild scanning dysarthria, nystagmus, slow saccades without oculo-motor apraxia and hyporeflexia. Moderate cerebellar tremor, mild scanning dysarthria, nystagmus, slow saccades without oculo-motor apraxia and hyporeflexia His total ataxia score evaluated by the International Cooperative Ataxia Rating Scale (ICARS) was 17/100. Molecular studies of frataxin and aprataxin genes ruled out Friedrich ataxia and cerebellar ataxia with oculomotor apraxia 1 (AOA1) His older brother (P2) had normal neurologic examination at 14 years, but at the age of 18 years he started to develop cerebellar signs with impaired gait, dysmetria, ataxia of the trunk, dysarthria, hyporeflexia and slow saccades with oculomotor apraxia. No mutation was found in P1 and P2 asymptomatic siblings, who had normal peroxisomal parameters in plasma and no neurologic symptoms

Discussion

Conclusion