ANKYRIN BUGEY - A DE-NOVO DELETIONAL FRAMESHIFT VARIANT IN EXON-6 OF THE ANKYRIN GENE ASSOCIATED WITH SPHEROCYTOSIS

We describe a case of spherocytosis in a French child splenectomized a t age 10 years, The parents were devoid of any clinical, hematological , or biochemical abnormalities, Following splenectomy, the proposita e xhibited a reduction of red cell membrane ankyrin. The variable number of dinucleotide repeats associated with the erythroid ankyrin gene (A NK1) were studied at the genomic level. The father, the mother, and th e proposita had the AC(14)/AC(11), AC(14)/AC(14), and AC(14)/AC(11) ge notypes, respectively, although the proposita exhibited a pattern cons istent with an AC(14)-combination at the cDNA revel. We thought there could be a de novo mutation in the ANK1 allele of paternal origin (AC( 11)). A false paternity seemed most unlikely. Based on PCR-amplificati on of exons, SSCP analysis, and, when appropriate, nucleotide sequenci ng, we found a one nucleotide deletion in codon 146 (exon 6): 521delC, ACG-->AG. This placed in phase a TAG triplet normally overlapping cod ons 150 and 151. Early interruption of translation presumably accounte d for the premature degradation of mutant mRNA. Restriction analysis c onfirmed the presence of the mutation in the proposita and its absence in the parents, The variant was designated ankyrin Bugey. (C) 1997 Wi ley-Liss, Inc.