Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia.
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.
Schüle
Rebecca
R
Sektion Klinische Neurogenetik, Hertie Institut für Klinische Hirnforschung, Tübingen, Germany.
Brandt
Elisabeth
E
Karle
Kathrin N
KN
Tsaousidou
Maria
M
Klebe
Stephan
S
Klimpe
Sven
S
Auer-Grumbach
Michaela
M
Crosby
Andrew H
AH
Hübner
Christian A
CA
Schöls
Ludger
L
Deufel
Thomas
T
Beetz
Christian
C
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8; D000072474:Cytochrome P450 Family 7; D004252:DNA Mutational Analysis; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*; D055815:Young Adult
D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human