ClinVar

Hereditary Sensory and Autonomic Neuropathy, Type IA

In a girl, born of nonconsanguineous parents, with hereditary sensory and autonomic neuropathy type I (HSAN1A; 162400), Auer-Grumbach et al. (2013) identified a de novo heterozygous c.922G-T transversion in the SPTLC1 gene, resulting in a ser311-to-tyr (S311Y) substitution. The mutation segregated with the disorder in the family and was not found in 1,969 individuals in an in-house database. The girl had a severe form of the disorder, with onset at age 4 years of unsteady gait, hand tremor, progressive sensory disturbances, and a pes cavus foot deformity necessitating triple arthrodesis at age 5. Disease progression was rapid and led to severe scoliosis, respiratory problems, and wheelchair dependence at age 14. She had prominent growth retardation but normal intellectual development. The level of 1-deoxySL was significantly elevated in the patient's plasma. Auer-Grumbach et al. (2013) noted that a different mutation at ser331 in the SPTLC1 gene (S331F; 605712.0005) resulted in a severe form of the disorder in 2 patients with HSAN1. They confirmed increased 1-deoxySL formation in HEK293 cells expressing the S331Y or the S331F mutant. Canonical serine activity was reduced by 60% in both mutants.

Juvenile Amyotrophic Lateral Sclerosis 27

In a patient (patient 3) with juvenile amyotrophic lateral sclerosis-27 (ALS27; 620285), Johnson et al. (2021) identified heterozygosity for the S331Y mutation. The mutation was identified by whole-exome sequencing and shown to be de novo. The patient had prominent motor symptoms and modest sensory autonomic symptoms.