Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia

作者：Schuele Rebecca; Brandt Elisabeth; Karle Kathrin N; Tsaousidou Maria; Klebe Stephan; Klimpe Sven; Auer Grumbach Michaela; Cro**y Andrew H; Huebner Christian A; Schoels Ludger; Deufel Thomas; Beetz Christian^*

来源：Neurogenetics, 2009, 10(2): 97-104.

DOI：10.1007/s10048-008-0158-9

• CYP7B1
• Hereditary spastic paraplegia
• Polymorphism
• SPG5

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.

• 出版日期2009-4