Distal Hereditary Motor Neuropathy, Type 7A via the SLC5A7 Gene

Distal hereditary motor neuropathy type 7A (HMN 7A, OMIM 158580) was described by Young and Harper (J Neurol Neurosurg Psychiatry 43(5):413-418, 1980) in a 5 generation family presenting with a unique form of spinal muscular atrophy characterized by onset in the teens and vocal cord involvement. Progression of the disease was slow and unrelenting, leading to significant loss of function of the hands and impaired ambulation. Muscles of the upper distal extremities were affected first, followed by wasting and weakness of muscles of the lower extremities. Toe walking and high arched feet were noted and sensory involvement was absent. Affected family members experienced stiffness and curling of the fingers, painful cramps, and shortness of breath. Vocal cord paralysis was an almost universal finding. Vocal cord involvement ranged from hoarse voice to bilateral cord palsy to bilateral paralysis (Young, I.D. and Harper, P.S., 1980).

Distal hereditary motor neuropathy type 7A is inherited as an autosomal dominant disorder. The SLC5A7 gene encodes a choline transporter which functions to supply choline at the neuromuscular junction. To date, only one mutation of the SLC5A7 gene (OMIM 608761) has been reported in one multigenerational family (Barwick, K.E. et al. Am J Hum Genet 91(6):1103-1107, 2012). The reported mutation imparts a dominant negative effect resulting in reduced choline uptake at the neuromuscular junction.

Too few cases of HMN 7A have been reported to estimate clinical and analytical sensitivity.

This test provides full coverage of all coding exons of the SLC5A7 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).