Two Novel Variants in PI4KA in a Family Presenting With Hereditary Spastic Paraparesis: A Case Report

Jevin Parmar, Elyshia Rowles, Phillipa Lamont, Kishore R. Kumar, Marion Stoll, Audrey Rick V, Pak Leng Cheong, Gina Ravenscroft

Research output: Contribution to journalArticlepeer-review


To report novel biallelic PI4KA variants in a family presenting with pure hereditary spastic paraparesis.

Two affected sisters presented with unsolved hereditary spastic paraparesis and underwent clinical and imaging assessments. This was followed by short-read next-generation sequencing.

Analysis of next-generation sequencing data uncovered compound heterozygous variants in PI4KA (NM_058004.4: c.[3883C>A];[5785A>C]; p.[(His1295Asn);(Thr1929Pro)]. Using ACMG guidelines, both variants were classified as likely pathogenic.

Here, next-generation sequencing revealed 2 novel compound heterozygous variants in the phosphatidylinositol 4-kinase alpha gene (PI4KA) in 2 sisters presenting with progressive pure hereditary spastic paraparesis. Pathogenic variants in PI4KA have previously been associated with a spectrum of disorders including autosomal recessive perisylvian polymicrogyria, with cerebellar hypoplasia, arthrogryposis, and pure spastic paraplegia. The cases presented in this study expand the phenotypic spectrum associated with PI4KA variants and contribute new likely pathogenic variants for testing in patients with otherwise unsolved hereditary spastic paraparesis.
Original languageEnglish
Number of pages6
JournalNeurology: Genetics
Issue number3
Publication statusPublished - Jun 2024


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