Complete APTX deletion in a patient with ataxia with oculomotor apraxia type 1

BMC Medical Genetics

Ans M.W. van den Ouweland¹  Raoul van de Graaf¹  Robert van der Helm¹  Galhana M. Bolman¹  Peter Elfferich¹  Grace Yoon²  Conxita Escofet³  Miriam Guitart³  Rick van Minkelen¹ 

[1] Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands;Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Canada;Genetic Laboratory, UDIAT-Centre Diagnòstic, Neuropediatrics Unity, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain

关键词: Genetic testing;    Breakpoint mapping;    SNP array analysis;    MLPA;    Homozygous;    Deletion;    Ataxia with oculomotor apraxia type 1;    APTX;   

Others  :  1223193
DOI  :  10.1186/s12881-015-0213-y

 received in 2014-12-12, accepted in 2015-08-11,  发布年份 2015

【 摘 要 】

Background

Ataxia with oculomotor apraxia type 1 is an autosomal-recessive neurodegenerative disorder characterized by a childhood onset of slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. Ataxia with oculomotor apraxia type 1 is caused by bi-allelic mutations in APTX (chromosome 9p21.1).

Case presentation

Our patient has a clinical presentation that is typical for ataxia with oculomotor apraxia type 1 with no particularly severe phenotype. Multiplex Ligation-dependent Probe Amplification analysis resulted in the identification of a homozygous deletion of all coding APTX exons (3 to 9). SNP array analysis using the Illumina Infinium CytoSNP-850 K microarray indicated that the deletion was about 62 kb. Based on the SNP array results, the breakpoints were found using direct sequence analysis: c.-5 + 1225_*44991del67512, p.0?. Both parents were heterozygous for the deletion. Homozygous complete APTX deletions have been described in literature for two other patients. We obtained a sample from one of these two patients and characterized the deletion (156 kb) as c.-23729_*115366del155489, p.0?, including the non-coding exons 1A and 2 of APTX. The more severe phenotype reported for this patient is not observed in our patient. It remains unclear whether the larger size of the deletion (156 kb vs 62 kb) plays a role in the phenotype (no extra genes are deleted).

Conclusion

Here we described an ataxia with oculomotor apraxia type 1 patient who has a homozygous deletion of the complete coding region of APTX. In contrast to the patient with the large deletion, our patient does not have a severe phenotype. More patients with deletions of APTX are required to investigate a genotype-phenotype effect.

【 授权许可】

   
2015 van Minkelen et al.

【 图 表 】

Fig. 1.

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