Two novel homozygous mutations of CAPN1 in Chinese patients with hereditary spastic paraplegia and literatures review

Fang Peng†,
Yi-Min Sun†,
Chao Quan,
Jian Wang and
Jian-Jun WuEmail author View ORCID ID profile

†Contributed equally

Orphanet Journal of Rare Diseases201914:83

https://doi.org/10.1186/s13023-019-1053-1

Received: 28 August 2018
Accepted: 25 March 2019
Published: 25 April 2019

Abstract

Background

Hereditary spastic paraplegias (HSP) are of great clinical and genetic heterogeneity. According to the clinical features, HSP can be divided into pure or complicated subtypes which combined with other neurological symptoms including cerebellar ataxia. Up to date, 78 loci or genes have been implicated in HSP. CAPN1 was a novel gene detected recently for spastic paraplegia 76 (SPG76).

Methods

Patients referred to our clinic with spastic or spastic-ataxic gait were collected. Genetic testing of the probands were performed by target sequencing of a panel containing over 4000 known virulence genes. And the candidate mutations were further confirmed by polymerase chain reaction (PCR) and Sanger sequencing. The clinical materials of these patients were demonstrated retrospectively.

Results

Two Chinese patients, both from consanguineous families, each carried a novel homozygous mutation of CAPN1, p.R48X and p.R339X. The male proband presented pure HSP subtype while the female proband presented complicated HSP symptoms with cerebellar ataxia. We then reviewed all the literatures of HSP patients carrying CAPN1 mutations and summarized the molecular spectrum and clinical characteristics of CAPN1-related SPG76.

Conclusion

These two SPG76 patients carrying CAPN1 mutations were the first reported in China. By reviewing the clinical manifestations of SPG76 patients, we validated the “spastic-ataxia” phenotype and emphasized the association between spasticity and ataxia, indicating the importance of CAPN1 screening in HSP patients.