A de novo c.113 T > C: p.L38R mutation of SPTLC1: case report of a girl with sporadic juvenile amyotrophic lateral sclerosis

Abstract

SPTLC1 has been implicated in hereditary sensory and autonomic neuropathy type 1 (HSAN1) and macular telangiectasia type2. Recent studies have reported mutations in SPLTC1 may cause juvenile amyotrophic lateral sclerosis (JALS), especially in the first transmembrane domain of SPTLC1(exon 2). In this study, we identified a novel heterozygous variant in exon 2, c.113 T > C: p. Leu38Arg, of SPTLC1 in a 12-year-old girl with sporadic JALS who experienced early-childhood-onset lower extremity spasticity followed by slowly progressive lower motor weakness and atrophy without sensory symptoms or signs. SPLTC1 is the first monogenic lipid metabolic disturbance that has been linked to ALS. The variant in exon 2 may impact on negative regulation of sphingolipid biosynthesis.

Keywords:

• Genetics
• genotype
• juvenile amyotrophic lateral sclerosis
• phenotype
• SPTLC1

Acknowledgments

We thank the family for their consent and participation in this study. We thank Running Gene Inc, (Beijing, China) for genetic sequencing and proofreading.

Authors contributions

Xiaoxuan Liu and Dongsheng Fan conceived and designed the study. Ji he provided valuable clinical materials. Xiaoxuan Liu and Weiyi Yu performed the genetic testing. Xiaoxuan Liu and Ji he wrote the paper. Dongsheng Fan reviewed and edited the manuscript. All authors read and approved the manuscript.

Ethics approval

The Institutional Ethics Committee of Peking University Third Hospital (PUTH) approved this study (IRB 00006761).

Consent for publication

A consent to publish form was signed by all patients included in our study.

Declaration of interest

The authors declare that they have no conflicts of interest.

Data availability statement

All the data and material in this article are publicly available and can be found at http://www.mono-mybg.com/jzjy-cmt.

Additional information

Funding

This study was supported by the Key R & D plan of Department of Science and Technology (No. XZ202001ZY0005G). This study was supported by Peking University Clinical + X youth program (2021–2022): PKU2021LCXQ019. This study was supported by National natural science foundation of China: 81873784,82071426.