Studies delineating the homozygous insertion mutation in MSH6. (A) Insertion of single base in mutant allele (A, highlighted in red) causes frame-shift and a premature termination codon (X, highlighted in red). (B) Sanger traces showing homozygous insertion of base A from the affected children and heterozygous insertion from the parents. (C) Immunostaining for MSH6 showing loss of normal nuclear staining in the lymphoma cells. (D). Immunostaining for MLH1 showing normal nuclear staining in tumor cells. The results were similar with MSH2 and PMS2 immunostaining (data not shown).