A novel form of distal hereditary motor neuronopathy maps to chromosome 9p21.1-p12

Distal hereditary motor neuronopathies (dHMNs) form a heterogeneous group o f rare disorders characterized by distal weakness and wasting in the limbs with no significant sensory involvement. Harding has classified dHMNs into seven categories based on clinical and genetic criteria. We report a novel form of autosomal recessive dHMN in 7 consanguineous families located in th e Jerash region of Jordan. Onset of the disease is between 6 and 10 years o f age and is characterized by weakness and atrophy of the lower limbs assoc iated with pyramidal features. Within 2 years, symptoms progress to the upp er limbs. Neurophysiological studies typically show normal conduction veloc ities, reduced compound motor action potential amplitudes, normal sensory n erve action potentials, and chronic neurogenic changes on needle electromyo graphy. No significant abnormalities are seen on sural nerve biopsy. We cal l this novel form of dHMN Jerash hereditary motor neuronopathy. We studied the families at the molecular genetic level and mapped the Jerash hereditar y motor neuronopathy gene to an approximately 0.54-cM region on chromosome 9p21.1-p12, flanked by microsatellite polymorphic marker loci D9S1845 and D 9S1791. A maximum LOD score of 19.80 at theta = 0.001 was obtained between the disease and locus D9S1878.