Objective: The objective was to describe the genetic and clinical findings in a Turkish girl, her father and paternal uncle carrying a novel homozygous HPCA mutation.

Background: Recent research has highlighted the role of HPCA in autosomal recessive torsion dystonia (DYT2). However, knowledge about genotypes and phenotypes in this HPCA‐related dystonia is still scarce.

Method: Whole-exome sequencing of the affected girl was performed after clinical, laboratory and MR radiological work-up without indicative results.

Results: The affected girl presented at the age of 2 years with gross motor unsteadiness, since then she developed dysarthria and dystonic posturing of the neck and lower limbs. Her father and paternal uncle are presenting different dystonic and choreatic features since childhood.Whole-exome sequencing revealed a novel homozygous mutation in the HPCA gene, c.182C>T p.(Ala61Val), affecting an evolutionarily highly conserved alanine residue within the EF-hand 2 domain of the neuron-specific calcium-binding protein hippocalcin. The unaffected mother was found to be a heterozygous carrier of the mutation, whereas the mutation was also homozygous in the father and his brother.

Conclusion: The family presenting with dystonia, dysarthria and a novel familial HPCA mutation phenomenological resembles the previously reported DYT-HPCA families thus expanding the genetic spectrum of DYT-HPCA dystonia described by Charlesworth et al. in 2015. Hence our findings support the role of HPCA mutations in autosomal recessive dystonia and highlight the need for further HPCA gene studies in cohorts with isolated and combined early onset recessive dystonia.

References: Charlesworth G, Angelova PR, Bartolomé-Robledo F, Ryten M, Trabzuni D et al. Mutations in HPCA cause autosomal-recessive primary isolated dystonia. Am J Hum Genet. 2015 Apr 2;96(4):657-65.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-familial-hpca-mutation-associated-with-autosomal-recessive-dystonia-strengthening-the-role-of-hpca-in-hereditary-movement-disorders/