Cause

This autosomal recessive condition trait to chromosome 2q24.3. This region contains the gene SCN9A, encoding the α-subunit of the voltage gated sodium channel, Na_v1.7, which is strongly expressed in nociceptive neurons. Sequence analysis of SCN9A in affected individuals revealed 3 distinct homozygous nonsense mutations:

ü W897X: Located in the P-loop of domain 2

ü 1767X: Located in the S2 segment of domain 2

ü S459X: Located in the linear region between 1 &2

This results in a truncated non-functional protein. Na_v1.7 channels are expressed at high levels in nociceptive neurons of the ‘dorsal root ganglia’. As these channels are likely involved in the formulations and propagation of action potentials in such neurons, it is expected that loss of function mutation in SCN9A will lead to abolished nociceptive pain propagation.