Biomedical subjects

David C W Russo

Publications and source records attributed to David C W Russo.

2 recordsLinked to original sources

PubMed2003

Mutations that diminish expression of Kell surface protein and lead to the Kmod RBC phenotype.

BACKGROUND: Kmod is an inherited rare RBC phenotype characterized by weak but detectable expression of high-incidence Kell antigens. STUDY DESIGN AND METHODS: The 19 exons and the intron-exon regions of the KEL gene from four unrelated Kmod individuals were sequenced and compared to wild-type KEL. To study the mechanisms by which the mutations result in depression of Kell antigens, mutant and wild-type Kell proteins were expressed in 293T cells and the amounts of protein present on the cell surface were determined. RESULTS: The following point mutations were identified: Kmod-1, homozygous 1208G>A, S363N; Kmod-2, heterozygous, 1208G>A, S363N and 2150 A>G, Y677C; Kmod-3 (previously classified as KEL:-13), heterozygous 1106T>C, L329P and 1716G>A, W532Stop; Kmod-4, heterozygous, 2227G>A, G703R and a silent 1839C>T mutation. In transfected 293T cells, fewer G703R and L329P mutant Kell proteins were transported to the cell surface compared with wild-type Kell protein, and there was no detectable Y677C mutant Kell protein. Previously, it was shown that that S363N Kell protein was not detected on the cell surface. CONCLUSION: Different point mutations, causing amino acid substitutions and presumably altering protein conformation, inhibit transport of the mutant Kell proteins to the cell surface. The different mutations leading to the Kmod phenotype explain why anti-Ku made by persons with the Kmod phenotype are not mutually compatible.

Amino Acid Substitution↗

PubMed2002

Point mutations causing the McLeod phenotype.

BACKGROUND: The McLeod phenotype is defined by absence of Kx, weakening of Kell system antigens, and acanthocytosis. Individuals with the McLeod phenotype usually develop late-onset neuromuscular abnormalities. Gene deletions, insertions, and point mutations that affect RNA splicing or that lead to premature stop codons have been reported to cause the McLeod phenotype. The McLeod phenotype may also be caused by mutations at a different splice site and by a novel mutation encoding an amino acid substitution that prevents transport to the cell surface. STUDY DESIGN AND METHODS: The coding and flanking intron regions of XK from four male, unrelated individuals with the McLeod phenotype and non-chronic granulomatous disease were sequenced and compared with the wild type sequence. Genomic DNA was amplified by PCR, and the products were sequenced. In one case, the mutant cDNA was expressed in a heterologous cell, and cell surface expression was determined. RESULTS: Three individuals with the McLeod phenotype had mutations that disrupted conserved GT sequences present at RNA splice sites. Two of them had G>C mutations at the 5' splice site of intron 1, and one had a G>A mutation at the 5' splice site of intron 2. One person with the McLeod phenotype had a 746C>G mutation in exon 3 encoding an R222G substitution. In a transfected cell, the expressed protein from the latter mutant did not travel to the cell surface. CONCLUSION: The McLeod phenotype may be caused by several different mutations.

Acanthocytes↗