||Hereditary sensory neuropathy, type 1
||common in clinvar
rs119482081, also known as c.398G>A, p.Cys133Tyr and C133Y, represents a rare mutation in the SPTLC1 gene on chromosome 9.
Inherited in a dominant manner, the rs119482081(A) mutation causes hereditary sensory neuropathy, type 1. This particular mutation is best known as the one carried by the Deater family, a large extended kindred originally from Germany but now living primarily in Pennsylvania and adjacent states of the US. This family has established the Deater Foundation, dedicated to research and treatment of hereditary neuropathies such as those caused by their and other SPTLC1 gene mutations.[PMID 11242106]; news article
As reported in [PMID 12417569], in this family, the age of onset of the disease is usually in the second or third decade. The symptoms begin with subtle loss of pain and temperature perception and are followed by ulcers in the toes and fingers. Symptom onset is earlier and progresses faster in men than in women. Absence of a pinprick response is observed in the early teens, even in asymptomatic patients carrying the disease haplotype. Muscle weakness and atrophy are eventually evident in most patients and may be very severe, requiring mechanical assistance such as the use of splints and crutches. In the advanced cases, sensory potentials are absent, and motor nerve conduction velocities are decreased in the lower extremities.