Biallelic PIGB Variants Cause Motor Neuropathy with Conduction Blocks and Peripheral Nerve Hyperexcitability.

PIGB

Biallelic PIGB variants impairing GPI-anchored protein expression; consistent reduction of free GPI in blood cells

Inherited glycosylphosphatidylinositol (GPI) deficiencies are known as early-onset multisystem disorders. The authors describe 12 patients (median age 32 years) from 9 independent families carrying biallelic PIGB variants (15 variants, 13 of them novel, including a de novo inversion generating a PIGB::RAB27A fusion). Ten patients had distal lower-limb weakness, with a motor-predominant neuropathy and conduction blocks in all, and signs of nerve hyperexcitability in 9. Three patients showed a decremental response on repetitive stimulation, 2 of them symptomatic and responding to pyridostigmine, and the novel variants impaired GPI-anchored protein expression in vitro.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The practical message is to consider PIGB and the other GPI-pathway genes in motor neuropathy with conduction blocks, an adult phenotype very different from the known multisystem presentations. The pyridostigmine response concerns only 2 patients and remains an observation to confirm. The PIGB::RAB27A fusion from an inversion illustrates the value of genome sequencing in such cases.

Analysis by Dr Thibaut Benquey