Compound heterozygous P67S/D91A SOD1 mutations in an ALS family with apparently sporadic case

Abstract

Objectives: To describe a family with heterozygous P67S and D91A SOD1 mutations. Methods: The ALS profile of the proband was described. SOD1 gene sequencing was performed in the proband and his children. Results: The affected individual presented with progressive left peripheral facial palsy and slow progression with late limb involvement. Unequivocal upper and lower motor neuron signs were present, together with diffuse denervation at myography. The absence of trigeminal involvement excluded a FOSMN syndrome. Pedigree analysis did not show any other ALS case in the family. Genetic analysis of this patient showed P67S and D91A SOD1 mutations. The genetic analysis of the children showed that the mutations were each one carried by a different chromosome. Conclusions: P67S SOD1 mutation has been described in several ALS cases, either with familial or apparently sporadic ALS. The mutation is located in a mutational hotspot and was predicted pathogenic by in silico prediction software. The study of phylogenetic data show that at this codon, the proline is highly conserved throughout species reinforcing causality. Conversely, the D91A variant is known to have a recessive influence. Unilateral motor facial involvement, even after several years, in an ALS patient is unusual. The present case with compound heterozygosity and unusual onset in a patient with apparently sporadic ALS, widens the clinical spectrum of the disease and adds further arguments to support the systematic genetic screening of all ALS cases in referral ALS clinics.

Keywords:

• ALS
• SOD1
• mutation
• compound heterozygous
• peripheral facial palsy

Ethical approval

This work was approved by the Institutional Review Board of the CHU of Montpellier, number: IRB-MTP_2021_05_202100837.

Declaration of interest

The authors report no conflicts of interest.

Author contributions

Clinical data: ED, WC. Genetic analysis: AP, CG, KM, SL. Writing of the manuscript: WC, ED, KM, SL, CG. Critical revision of the manuscript: AP, CG, ED, FE, KM, NP, SL, WC.

Data availability statement

Data are available on request to the corresponding.