Three novel mutations in 20 patients with hereditary spastic paraparesis
Hereditary spastic paraparesis (HSP) constitutes both genetic and clinically heterogeneous group of upper motor neuron diseases. Half of the individuals with autosomal dominant (AD) HSP have mutations in SPAST, ATL1, and REEP1 genes. This study was conducted to elucidate the genetic etiology of patients with the pure type AD-HSP diagnosis. The patient group consisted of 23 individuals from 6 families in Turkey. In the first step of work, Sanger sequencing (SS) was performed in ATL1, SPAST, and REEP1 genes and the second phase whole-exome sequencing (WES) was performed following SS analysis for the patients with no detected mutations in these genes. The results of this study revealed that in ATL1, 6 patients have previously reported c.776C > A mutation and 6 patients have novel c.470 T > C mutation. In SPAST, 3 patients have novel c.1072G > C mutation and 2 patients have novel c.1099-1G > C mutation. WES was performed in three patients, who had no detected mutation in these genes with SS analysis. In this approach, as previously reported c.1859 T > C mutation in KIAA0196 was detected, and it was confirmed with the patient’s relatives by SS. In three of patients, no HSP-associated variant could be identified in SS and WES. With this study, the molecular genetic etiology in 20 of 23 (87%) individuals that were included in this study with the utilization of SS and WES was elucidated. Utilization of SS and WES methods have enabled the identification of genetic etiology of HSP further with appropriate genetic counseling that was provided to the patients.
KeywordsHereditary spastic paraparesis Novel mutation Whole-exome sequencing Genetic heterogeneity
We are grateful to the families and individuals for their participation in this study and to the physicians and staff members of the Department of Medical Genetics and Neurology, Cerrahpaşa Medical School, Istanbul University-Cerrahpaşa, for their involvement in the management of the patients. Also, we thank Dr. Selcuk Sozer Tokdemir for the valuable inputs and reviews.
This work was supported by the Istanbul University Scientific Research Projects Unit. (Grant number: 22323).
Compliance with ethical standards
The study protocol was approved by the Istanbul University Institutional Review Board for Research with Human Participants. Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare that they have no conflict of interest.
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