The first case of spastic ataxia type 4 associated with heterozygous mutations in MTPAP gene

Objective MTPAP is a nuclear-encoded polymerase that synthesizes homopolymeric poly(A) tails on mitochondrial mRNAs which is important to maintain mitochondrial gene expression.MTPAP gene mutations are related with spastic ataxia type 4 which is first described in Old Amish family members who have homozygous MTPAP mutation.This is a neurodegenerative condition with cerebral ataxia(limb and truncal),spastic paraparesis,cerebellar and spastic dysarthria,learning difficulties and optic atrophy.Autosomal recessive perinatal encephalopathy with lethality in the first year of life related with homozygous MTPAP mutation was described recently. Method Here,we describe the first case of a child carrying heterozygous mutation in MTPAP gene and presenting with only spastic paraparesis. Results A seven-year-old male who is the second child of healthy and non-consanguineous parents.His complaints are tip toe walking and pain in the legs after walking for a while and being tired quickly on slope.The family history was unremarkable.His mental development is normal.He had no dysmorphic features,mild pes cavus deformity,spasticity,hyperreflexia in lover limb.Laboratory testing,including complete blood count,creatine kinase,metabolic screening tests were normal.Electroencephalography,Denver developmental scale score,brain and spinal MRI were also normal.Whole exome sequencing showed heterozygous p.L285fs*4(c.853delC) mutation in MTPAP gene. Conclusion Up-to-date all reported 6 cases with MTPAP mutations related with spastic ataxia are always seen as a homozygous form but,in this case,heterozygous MTPAP gene mutation caused mild form of spastic ataxia.We thought that heterozygous MTPAP mutation may cause autosomal dominant form spastic ataxia type 4 with mild clinical findings.However the mother has also the same variant in heterozygous state,there has been still an unclarified genetic situations such as incomplete penetrance or variable expression patterns.
Keywords: MTPAP,spastic ataxia type 4, paraparesis, CK, gait disturbances