Ankyrin Napoli: a de novo deletional frameshift mutation in exon 16 of ankyrin gene (ANK1) associated with spherocytosis

• Published in: British journal of haematology Vol. 93; no. 4; p. 828
• Main Authors: del Giudice, E M, Hayette, S, Bozon, M, Perrotta, S, Alloisio, N, Vallier, A, Iolascon, A, Delaunay, J, Morlé, L
• Format: Journal Article
• Language: English
• Published: England 01.06.1996
• Subjects: Amino Acid Sequence; Ankyrins - genetics; Base Sequence; Child; Erythrocyte Membrane - metabolism; Exons; Female; Frameshift Mutation; Humans; Molecular Sequence Data; Mutation; Polymorphism, Genetic; Spherocytosis, Hereditary - genetics
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1996.d01-1746.x

We report a case of apparently recessive hereditary spherocytosis in an Italian child. The proband exhibited a reduction of overall ankyrin in the red cell membrane. The parents were free of any haematological manifestations. The VNDR associated with the ankyrin gene (ANK1) were consistent with the following diplotypes: AC11/ AC14 (father), AC14/AC14 (mother) and AC11/AC14 (child). The cDNA of the patient disclosed the expression of the AC11 allele only. As a consequence, we put forward the hypothesis of a de novo inactivation affecting the ankyrin allele of maternal origin (AC14) and accounting for the disease. PCR amplification of exons, SSCP analysis and nucleotide sequencing disclosed a polymorphism: GAC --> AAC; Asp --> Asn in codon 328 of exon 10, and a one-nucleotide deletion : CTG --> CG in codon 573 of the exon 16. This frameshift mutation placed in phase the TGA triplet that normally overlaps codons 636 and 637. Termination of translation near the middle of ankyrin mRNA coding sequence resulted, presumably, in its premature degadation. The present allele has been designated allele Napoli.