Abstract
Hereditary spastic paraplegia (HSP) refers to a group of genetic disorders characterized by progressive weakness and stiffness in the muscles of the legs. To date, more than 83 types of HSP exist, differing in their etiology, their degree of severity, and the nature of symptoms associated with each of these conditions. Owing to their genetic and clinical heterogeneity, the establishment of an accurate diagnosis can be very challenging, especially with the clinical overlap observed between those conditions and other neurogenetic diseases. A 7-year-old girl, born to a consanguineous Iraqi family, was referred to us for clinical and genetic evaluation. The patient presents with progressive difficulty in walking that started when she was 3 years old, lower limb predominant spastic paraparesis, and mild upper limbs involvement with slight tremor in the hands, all occurring in the absence of neurodevelopmental or growth delays. Whole exome sequencing revealed a novel homozygous missense variation in the RNF170 gene (NM_030954.3; p.Cys107Trp), thus establishing the diagnosis of HSP. Here, we report the second missense biallelic variation in RNF170 and we discuss thoroughly all previously reported cases with RNF170-linked HSP.
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The datasets used and analyzed during the current study are available from the corresponding author upon a reasonable request.
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We express our deepest gratitude and sympathy to the family for their full cooperation throughout the study.
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EC, CM, and AM conceived, designed the study, performed data interpretation, and wrote the manuscript. All authors have read and approved the manuscript.
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Approval to conduct the study was obtained from the Institutional Review Board of the Lebanese American University, Beirut, Lebanon. Parents signed an informed consent for participation and sample collection.
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Chouery, E., Mehawej, C. & Megarbane, A. A novel homozygous variant in RNF170 causes hereditary spastic paraplegia: a case report and review of the literature. Neurogenetics 23, 85–90 (2022). https://doi.org/10.1007/s10048-022-00685-6
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DOI: https://doi.org/10.1007/s10048-022-00685-6