Premium
Hereditary spastic paraplegia caused by compound heterozygous mutations outside the motor domain of the KIF1A gene
Author(s) -
Krenn M.,
Zulehner G.,
Hotzy C.,
Rath J.,
Stogmann E.,
Wagner M.,
Haack T. B.,
Strom T. M.,
Zimprich A.,
Zimprich F.
Publication year - 2017
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13279
Subject(s) - hereditary spastic paraplegia , paraplegia , compound heterozygosity , genetics , medicine , sanger sequencing , exome sequencing , spastic , mutation , genetic heterogeneity , gene , phenotype , bioinformatics , biology , physical medicine and rehabilitation , cerebral palsy , spinal cord , psychiatry
Background and purpose Hereditary spastic paraplegia is a clinically and genetically heterogeneous group of rare, inherited disorders causing an upper motor neuron syndrome with (complex) or without (pure) additional neurological symptoms. Mutations in the KIF 1A gene have already been associated with recessive and dominant forms of hereditary spastic paraplegia ( SPG 30) in a few cases. Methods All family members included in the study were examined neurologically. Whole‐exome sequencing was used in affected individuals to identify the responsible candidate gene. Conventional Sanger sequencing was conducted to validate familial segregation. Results A family of Macedonian origin with two affected siblings, one with slowly progressive and the other one with a more complex and rapidly progressing hereditary spastic paraplegia is reported. In both affected individuals, two novel pathogenic mutations outside the motor domain of the KIF 1A gene were found ( NM _001244008.1:c.2909G>A, p.Arg970His and c.1214dup, p.Asn405Lysfs*40) that segregate with the disease within the family establishing the diagnosis of autosomal recessive SPG 30. Conclusions This report provides the first evidence that mutations outside the motor domain of the gene can cause (recessive) SPG 30 and extends the genotype−phenotype association for KIF 1A ‐related diseases.