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

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.

A total of 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1 gene (SPG42)

“…Analysis of MLPA data was carried out as described previously. 15 RESULTS AND DISCUSSION HRM analysis detected an aberrant melting profile caused by an A4G substitution at position 512 of the coding sequence that causes a p. D171G substitution in 16 index patients (Figure 1). This sequence abnormality represents the known single-nucleotide polymorphism (SNP) rs3804769 according to the SNP database.…”

Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis

“…Cases 3 and 4 are nonconsanguineous siblings of Italian origin ( 3 ). Case 3 is a 42-year-old male who has suffered from pure HSP since the age of 11.…”

CYP7B1 Mutations in French-Canadian Hereditary Spastic Paraplegia Subjects

“…Moreover, additional family members were screened, when available, and there was no segregation of this variant with the disease. This mutation was considered by Schüle et al as a phenotype modifier of complex HSP phenotypes 5 ; we have no data to support this contention.…”