In a French Gypsy with hereditary sensory and autonomic neuropathy type I (HSAN1A; 162400), Rotthier et al. (2009) identified a de novo heterozygous 992C-T transition in the SPTLC1 gene, resulting in a ser331-to-phe (S331F) substitution in a conserved residue. The patient had an unusually severe phenotype, with congenital onset, insensitivity to pain with eschar and foot ulceration, pes cavus/equinovarus, vocal cord paralysis, and gastroesophageal reflux. The patient also had severe growth and mental retardation, microcephaly, hypotonia, amyotrophy, and respiratory insufficiency. Nerve conduction studies showed absent sensory and motor responses in the upper and lower limbs. The mutation was absent from 600 control chromosomes. The phenotype expanded the clinical spectrum of HSAN1.
Auer-Grumbach et al. (2013) reported that a patient with a severe form of HSAN1, originally described by Huehne et al. (2008) (patient ER-CIPA-20374), was found to be heterozygous for the S331F mutation in the SPTLC1 gene. The authors noted that another patient with a severe form of HSAN1 was heterozygous for a different mutation at ser311 in the SPTLC1 gene (S311Y; 605712.0007). Auer-Grumbach et al. (2013) confirmed increased 1-deoxySL formation in HEK293 cells expressing the S331F or the S331Y mutant. Canonical serine activity was reduced by 60% in both mutants.
