Genetic localization of a new locus for recessive familial spastic paraparesis to 15q13-15

Objective: To characterize a new gene locus for familial spastic paraparesi s (FSP), Background: FSP is a genetically heterogeneous group of upper moto r neuron syndromes. It can be inherited as an autosomal dominant, autosomal recessive, or X-linked disorder. Four loci for autosomal dominant FSP have been genetically mapped, and two genes have been shown responsible for the X-Linked type. In addition, two loci for autosomal recessive type have bee n reported and mapped to chromosomes 8q and 16q. The gene for the 16q locus has been characterized as a mitochondrial protein. Methods: Eight recessiv e FSP families from America and Europe were used for genetic linkage analys is. The known recessive loci (8q and 16q) and the X-linked loci (PLP and L1 CAM genes) were screened through PCR amplification, followed by Linkage ana lysis, single-strand conformational polymorphism, or both. Results: All the families except one revealed lack of linkage to the known loci for recessi ve and X-linked types of FSP, One of the eight families showed data consist ent with linkage to the previously characterized 8q locus. Analysis of all the families for possible linkage to other candidate loci revealed signific ant positive lod scores for markers in chromosome 15q. The maximum multipoi nt combined lod score for the non-8q families was Z = 3.14 for markers D15S 1007, D15S971, D15S118, and D15S1012, at a distance of 6.41 cM from the mar ker D15S1007, in between D15S971 and D15S118. Conclusions: Our data suggest a new locus for recessive FSP linked to chromosome 15q, and that this may be the most common one.