A study in Gene Encoding SLURP-1 Protein and Immunological Function in Taiwan Mal de Meleda Family
Date Issued
2008
Date
2008
Author(s)
Lin, Pei-Jung
Abstract
Mal de Meleda (MDM, OMIM 248300) is a rare autosomal recessive skin disorder characterized by glove- and sock-like erythrokeratosis on palms and soles with mutation of SLURP-1 gene. We reported a Taiwan MDM family and first found the association with impaired T cell activation in 1985. In the study, mutations of gene encoding SLURP-1 protein and lymphocytes proliferation tests were investigated in three generations of this family. We try to offer the genetic counseling to the members of MDM family and establish the ways for clinical diagnosis and therapy. CR-sequencing of SLURP-1 revealed 1764 (X99977) G to A mutation of exon 3 which changed the amino acid at number 86 from Glycine to Arginine (G86R). All of 4 affected members have homozygous mutation of 1764 A/A genotype On the other hand, among 15 members with normal skin phenotype were 7 of G/G genotype and 8 of G/A genotype.he T cell activation using anti-CD3/CD28 antibodies as stimulant is impaired in all 12 family members with heterozygous (G/A) or homozygous (A/A) 1764G>A mutation genotype. On the contrast, only 2 of 7 members with normal G/G genotype have impaired T-cell activation. (Chi-Square test with Yate’s correction, p=0.003)LURP-1 was induced in PBMBs of normal subjects with normal proliferation response to anti-CD3/CD28 antibodies stimulation, while the MDM family members with A/A or G/A genotype exhibit low proliferation response. Treatment with 0.5ug/ml recombinant-human SLURP-1 protein recovered T cell activation in patient with A/A genotype. This finding supports that SLURP-1 protein play a crucial role in T cell activation. or clinical diagnosis, the genetic consulting flow chart is an easy and directed screen to facing the new Mal de Meleda (MDM) or other recessive palmar plantar erythyrokeratodermia (PPK) families. Regarding the MDM affected members, progressive of erythema and hyperkeratosis on feet and soles is led them incapable wear shoes and walk after 50 years old. Sometimes, other skin infections of MDM affected members have been reported. The conditions of MDM affected members indeed should be paid attention to the team of social and medical work cooperation. In addition, for the Mal de Meleda (MDM) family members, it is important to keep on going with heterozygous 1764G>A mutation members and provide them genetic consultations and prenatal diagnosis plan to pregnancy.
Subjects
SLURP-1
G86A
anti-CD3/CD28
T cell activation
genetic consulting
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