TY  - JOUR
AU  - Rydning, S. L.
AU  - Dudesek, A.
AU  - Rimmele, F.
AU  - Funke, C.
AU  - Krüger, S.
AU  - Biskup, Saskia
AU  - Vigeland, M. D.
AU  - Hjorthaug, H. S.
AU  - Sejersted, Y.
AU  - Tallaksen, C.
AU  - Selmer, K. K.
AU  - Kamm, C.
TI  - A novel heterozygous variant in ERLIN2 causes autosomal dominant pure hereditary spastic paraplegia.
JO  - European journal of neurology
VL  - 25
IS  - 7
SN  - 1351-5101
CY  - Oxford
PB  - Blackwell Science78889
M1  - DZNE-2020-06331
SP  - 943-e71
PY  - 2018
AB  - Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous monogenic disorders. To date, nearly 70 genes are known to be causative. The aim of this project was to identify the genetic cause of autosomal dominantly inherited pure HSP in two large, unrelated non-consanguineous families.The two families were characterized clinically and selected members underwent whole exome sequencing. Potentially disease-causing variants were confirmed by Sanger sequencing and their functional consequences on protein function were predicted by bioinformatic prediction tools.The patients presented with pure spastic paraplegia with age of onset between 9 and 46 years. In both families, a novel heterozygous missense variant in ERLIN2, c.386G>C; p.Ser129Thr, was the only potentially pathogenic variant identified that segregated with the disease.Biallelic variants in ERLIN2 are known to cause recessive HSP type SPG18. Here, the first two families with an autosomal dominant, pure form of HSP caused by a novel ERLIN2 heterozygous missense variant are described. These findings expand the mutational and inheritance spectrum of SPG18. ERLIN2 variants should also be considered in the diagnostic evaluation of patients with autosomal dominant HSP.
KW  - Adult
KW  - Female
KW  - Heterozygote
KW  - Humans
KW  - Male
KW  - Membrane Proteins: genetics
KW  - Middle Aged
KW  - Mutation
KW  - Pedigree
KW  - Spastic Paraplegia, Hereditary: genetics
KW  - ERLIN2 protein, human (NLM Chemicals)
KW  - Membrane Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:29528531
DO  - DOI:10.1111/ene.13625
UR  - https://pub.dzne.de/record/140009
ER  -