Backround: Congenital insensitivity to pain (CIP) is a rare monogenic disorder of absence of pain perception and anosmia. CIP can be caused by mutations in different genes. In the inbred consanguineous Bedouin population of southern Israel there are several large kindreds affected with CIP due to a common founder mutation in NTRK1. A consanguineous Bedouin family presented with cases of CIP yet with no NTRK1 mutations. One of the affected individuals had also clinical and MRI findings compatible with the diagnosis of multiple sclerosis.
Objective: To unravel the molecular basis of congenital insensitivity to pain in a Bedouin family.
Design: Following IRB approval and informed consent, blood samples were obtained from the affected offspring, two obligatory carriers and five unaffected siblings. Whole exome sequence analysis was performed followed by verification and segregation analysis.
Results: Whole exome sequencing unraveled a novel homozygous nonsense mutation in SCN9A exon 6: c.1242 A > T (p.K301X). Sanger sequencing verified the mutation and its appropriate segregation within the affected family. The individual affected by both CIP and multiple sclerosis was also homozygous for the SCN9A mutation.
Conclusions: We describe a novel SCN9A mutation causing CIP. Interestingly, one of the individuals homozygous for the mutation had clinical manifestations of multiple sclerosis in addition to CIP. It remains to be seen whether the association of the multiple sclerosis phenotype with the SCN9A mutation is random or of significance in disease pathogenesis.
