The ABCB6 mutation p.Arg192Trp is a recessive mutation causing the Lan- blood type.

Area of Science:

• Genetics
• Immunology
• Molecular Biology

Background:

• The ATP-binding cassette subfamily B member 6 (ABCB6) protein functions as a membrane transporter.
• ABCB6 has been identified as the carrier of the high-frequency red blood cell (RBC) antigen Lan.
• Individuals with the Lan- blood type typically possess two recessive null mutations in the ABCB6 gene.

Observation:

• A family with the Lan- blood type across two generations was studied.
• Analysis focused on identifying mutations within the ABCB6 gene and assessing Lan antigen expression.
• Methods included Sanger sequencing, serology, flow cytometry, PCR-RFLP, and Western blot analysis.

Findings:

• All Lan- family members were homozygous for the ABCB6 missense mutation c.574C>T (p.Arg192Trp), while Lan+ members were heterozygous.
• Homozygosity for p.Arg192Trp resulted in the absence of both the Lan antigen and the ABCB6 transporter on RBC membranes.
• Five unrelated Lan- individuals were also homozygous for p.Arg192Trp and had developed anti-Lan antibodies.
• Three additional ABCB6 mutations (p.Arg276Trp, p.Phe29del, p.Gly588Ser) were identified as potential null alleles.

Implications:

• The p.Arg192Trp mutation is the first identified missense mutation causing the Lan- blood type and is a common cause of this rare phenotype.
• Like other ABCB6 null mutations, p.Arg192Trp acts recessively.
• Other single amino acid substitutions in ABCB6 may also lead to the Lan- blood type, expanding the known genetic basis of this blood group antigen.