Homozygous variant, p.(Arg643Trp) in VAC14 causes striatonigral degeneration: report of a novel variant and review of VAC14-related disorders

Parneet Kaur, Gandham Sri Lakshmi Bhavani, Arun Raj, Katta Mohan Girisha, Anju Shukla

Research output: Contribution to journalArticle


VAC14-related disorders include two distinct phenotypes, striatonigral degeneration [MIM# 617054] and Yunis–Varon syndrome. Striatonigral degeneration is a recently described childhood onset dystonia caused by pathogenic variants in VAC14. It is characterized by a period of apparent normalcy followed by abrupt onset neuroregression, dystonia, involuntary movements and degenerative brain lesions involving caudate nucleus, putamen and substantia nigra. Yunis–Varon syndrome is a well described severe condition characterised by skeletal findings and dysmorphism along with neuronal degeneration. Pathogenic variants in FIG4 have been previously reported to cause Yunis–Varon syndrome. Recently, loss of function variants in VAC14 were also reported in an individual affected with Yunis–Varon syndrome. Total seven individuals from four families are reported to have VAC14-related disorders till date. Here, we report another individual with clinical and radiological features suggestive of striatonigral degeneration with homozygous missense variant in VAC14. The patient fibroblasts showed extensive vacuolization, characteristic of VAC14-related disorders. We also review the phenotype and genotype associated with these disorders.

Original languageEnglish
Pages (from-to)1237-1242
Number of pages6
JournalJournal of Human Genetics
Issue number12
Publication statusPublished - 01-12-2019


All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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