Genome-widely significant evidence of linkage of schizophrenia to chromosomes 2p24.3 and 6q27 in an SNP-Based analysis of Korean families.

The present study reports the results of a genome-wide SNP linkage scan for schizophrenia in the Korean population. Fifty-six multiplex schizophrenia families were analyzed. Clinical evaluations on all subjects were consistently performed by raters in a single research team. Multipoint non-parametric linkage analysis was performed, and empirical simulations were generated to determine genome-wide significance. The authors found genome-widely significant evidence of linkage for schizophrenia to chromosomes 2p24.3 (NPL Z = 3.18) and 6q27 (NPL Z = 2.90). Six other chromosomal regions, that is, 3q24, 13q12.3, 18q22.3, 20p12.2, 4p14, and 1p36.12, yielded NPL Z scores of above 2.0 for either broad or narrow phenotype classes. Although linkage to these loci has not received prominent attention in studies on Caucasian families, multiple overlaps were observed between our loci (on 2p, 3q, and 13q) and linkage peaks generated from extended families in various isolated populations. Fine mappings and the detection of candidate genes within these regions are warranted.

A novel missense mutation (I344K) in the SPG4gene in a Korean family with autosomal-dominant hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower extremities. Among eight loci linked with autosomal-dominant (AD)-HSP, the SPG4 locus on chromosome 2p22 accounts for about 40% of all patients. Recently, mutations in a new member of the AAA protein family, called spastin, have been identified as responsible for SPG4-linked AD-HSP. Here, we describe a novel missense mutation (c.1031T>A; I344K) in exon 7 of the SPG4 gene identified in a Korean family with typical clinical features of pure AD-HSP. The mutation affects the third amino acid of the highly conserved AAA cassette domain, which is the most fore part of the domain altered by a missense mutation reported so far. Clinical presentations of affected individuals carrying the I344K mutation were not different from those of pure AD-HSP with SPG4 mutations reported previously. However, it is noteworthy that neither urinary dysfunction nor involvement of upper extremities was noticed in this family. To our knowledge, this is the first report of genetically confirmed AD-HSP in Korea.