Hereditary spastic paraplegia with thin corpus callosum: reduction of the SPG11 interval and evidence for further genetic heterogeneity.
BACKGROUND
Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) is an autosomal recessive form of complicated HSP mainly characterized by slowly progressive spastic paraparesis and mental deterioration beginning in the second decade of life. The locus for HSP-TCC, designated SPG11, was mapped to chromosome 15q13-15 in some of the affected families from Japan, Europe, and North America, spanning an interval of 17.5 megabases (Mb).


OBJECTIVE
To perform a clinical and genetic study of HSP-TCC.


METHODS
Case series; multi-institutional study.


METHODS
Seven patients with HSP-TCC who belong to 3 consanguineous families of Arab origin residing in Israel.


RESULTS
The 7 patients manifested a relatively similar combination of adolescence-onset cognitive decline and spastic paraparesis with TCC on brain magnetic resonance imaging. After excluding the SPG7 locus, we tested the 3 families for linkage to the SPG11, SPG21/MAST, and ACCPN loci associated with autosomal recessive disorders with TCC. Two families showed evidence for linkage to SPG11 (Z(max) = 5.55) and reduced the candidate region to 13 Mb.


CONCLUSIONS
Our findings in HSP-TCC further confirm its worldwide distribution and genetic heterogeneity, and they significantly reduce the candidate SPG11 interval.
Lossos
Alexander
A
Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. alos@hadassah.org.il
Stevanin
Giovanni
G
Meiner
Vardiella
V
Argov
Zohar
Z
Bouslam
Naima
N
Newman
J P
JP
Gomori
John M
JM
Klebe
Stephan
S
Lerer
Israela
I
Elleuch
Nizar
N
Silverstein
Shira
S
Durr
Alexandra
A
Abramsky
Oded
O
Ben-Nariah
Ziva
Z
Brice
Alexis
A