Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia |
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Authors: | Rebecca Schüle Elisabeth Brandt Kathrin N. Karle Maria Tsaousidou Stephan Klebe Sven Klimpe Michaela Auer-Grumbach Andrew H. Crosby Christian A. Hübner Ludger Schöls Thomas Deufel Christian Beetz |
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Affiliation: | Sektion Klinische Neurogenetik, Hertie Institut für Klinische Hirnforschung, Tübingen, Germany. |
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Abstract: | Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness. Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP patients (n = 12) as well as index patients from non-consanguineous families with recessive (n = 8) and dominant (n = 8) transmission of HSP. One sporadic patient showing HSP as well as optic atrophy carried a homozygous nonsense mutation. Compound heterozygosity was observed in a recessive family with a clinically pure phenotype. A heterozygous missense change segregated in a small dominant family. We also found a significant association of a known coding polymorphism with cerebellar signs complicating a primary HSP phenotype. Our findings suggest CYP7B1 alterations to represent a rather frequent cause of HSP that should be considered in patients with various clinical presentations. |
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Keywords: | CYP7B1 Hereditary spastic paraplegia Polymorphism SPG5 |
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