The MAP1B gene  is located on chromosome 5q13.2 and the protein is expressed in neural tissues in areas of high plasticity. MAP1B is associated with neuronal migration and axonal guidance.  MAP1B is the binding partner of gigaxonin encoded by GAN. Mutations in GAN are responsible for giant axonal neuropathy. GAN mutations affecting MAP1B binding regions result in a toxic buildup of MAP1B. Mutations in MAP1B have not yt been associated  with human disorders (OMIM).

The index case was an 18-year-old man who was noted to have nystagmus walking difficulty that began at the age of 4. Subsequently he developed progressive lower extremity weakness and ataxia. He was born of a consanguineous union and had a similarly affected brother and sister. On examination the patient was cognitively intact but dysarthric. Nystagmus was present.  Distal weakness and sensory loss were present in the lower extremities to a greater degree than the upper and deep tendon reflexes were diminished. Cerebellar signs were present. He had wiry hair.  His 17-year-old brother was similarly affected. Both had body mass indexes of greater than 40.  His sister was not available for assessment. Routine laboratory investigations were not remarkable. MRI of the brain and cords were normal. Nerve conduction studies revealed a severe sensory motor polyneuropathy. The index case, his bother and parents underwent whole exome sequencing (Saudi Diagnostic Laboratory, Riyadh Saudi Arabia).

Whole exome sequencing revealed the brothers carried novel homozygous mutations in MAP1B:NM_005909:exon5:c.5521A>G:p.M1841V. Both parents harbored heterozygous mutations.

Mutations in the MAP1B gene have not been previously reported to be pathogenic. We report a consanguineous family with a giant axonal neuropathy like phenotype that harbor a mutation in MAP1B and suggest that this mutation is responsible for this syndrome.