J Neurol (2004) 251 : 1085–1088 DOI 10.1007/s00415-004-0485-1 ORIGINAL COMMUNICATION Eleonora Cocco Maria Rita Murru Cristina Melis Lucia Schirru Elisabetta Solla Marina Lai Marcella Rolesu Maria Giovanna Marrosu PTPRC (CD45) C77G mutation does not contribute to multiple sclerosis susceptibility in Sardinian patients Introduction CD45 (protein-tyrosine phosphatase, receptor-type C) protein, encoded by a gene located on chromosome 1q31–32, is a major leukocyte cell surface molecule, in- volved in the activation of T and B cells and in integrin- mediated adhesion and migration of immune cells [17]. CD45 gene, encompassing 35 exons, is expressed in mul- tiple isoforms as a result of cell type-specific alternative splicing of exons 4, 5, 6 and 7 [18].Alternative splicing is regulated by at least two splicing enhancers and two splicing silencer elements within the exon 4 [10], al- though exon 6 significantly contributes to a correct splicing [23]. Both genetic and environmental factors make multi- ple sclerosis (MS) a complex disease. Recurrence risk and the lower risk found in adopted than in natural off- spring [4] demonstrate the importance of genetics. Sar- dinians are an insular Italian population genetically characterised by a low degree of large scale genetic het- erogeneity and by a distribution of alleles at multiple loci different from other Europeans [9]. In Sardinia, there is a very high incidence of MS (0.143 %) [6], which displays a peculiar HLA class II association [12].We re- cently reported that at the HLA-DR-DQ locus, five DRB1-DQB1 haplotypes, including the DRB1*0405- DQB1*0301 and DRB1*0301-DQB1*0201 haplotypes previously found in Sardinian MS [12] and the DRB1*1303-DQB1*0301 DRB1*1501-DQB1*0602 and DRB1*0405-DQB1*0302 haplotypes, were positively as- sociated with the disease [13]. It is likely that the high disease incidence on the island derives from the partic- ular genetic make-up of Sardinians and from the JON 1485 Received: 15 September 2003 Received in revised form: 22 December 2003 Accepted: 8 March 2004 E. Cocco · M. R. Murru · C. Melis · L. Schirru · E. Solla · M. Lai · M. Rolesu · M. G. Marrosu, M.D. () Dipartimento di Neuroscienze Centro Sclerosi Multipla Ospedale Binaghi Via Is Guadazzonis, 2 09126 Cagliari, Italy Tel.: +39-070/6092806 Fax. +39-070/6092929 E-Mail: gmarrosu@unica.it ■ Abstract A linkage and associa- tion of the CD45 (protein-tyrosine phosphatase, receptor-type C) C77G polymorphism and multiple sclerosis (MS) has been found in some studies but not in others.We analysed the C77G polymorphism in MS patients from the genetically homogeneous population of Sar- dinia. Using the transmission dis- equilibrium test, the mutation has been sought in 241 patients and 217 healthy sibs (HS) from single- ton MS families and it was found in 5 (2.07 %) affected and 3 (1.38 %) HS from 7 heterozygous parents (1.45%). Transmission of the G77 allele was 71.4 % (TDT = 1.3, P = 0.26) in patients and 50 % (TDT = 0, P = 1) in HS. Stratifying families according to carriage of MS-predisposing (DR+) or not- predisposing (DR–) HLA-DR-DQ genotype in patients, percentage of G77 transmission to DR+ patients was 33 (TDT = 0.33, P = 0.56, Pc = 1.12), while it was 100 (TDT = 4, P = 0.045, Pc = 0.09) in the DR-patients.We concluded that, despite the presence of CD45 G77 polymorphism in a few pa- tients who did not carry the HLA- DR-DQ MS-predisposing mole- cules, CD45 did not contribute to development of the disease in Sar- dinian MS. ■ Key words multiple sclerosis · CD45 · C77G point mutation