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A 5′ splice region G → C mutation in exon 3 of the human β‐spectrin gene leads to decreased levels of β‐spectrin mRNA and is responsible for dominant hereditary spherocytosis (spectrin Guemene‐Penfao)
Author(s) -
Garbarz Michel,
Galand Colette,
Bibas Dominique,
Bournier Odile,
Devaux Isabelle,
Harousseau JeanLuc,
Grandchamp Bernard,
Dhermy Didier
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00530.x
Subject(s) - hereditary spherocytosis , spectrin , exon , mutation , alternative splicing , gene , rna splicing , splice , microbiology and biotechnology , genetics , spherocytosis , epb41 , messenger rna , biology , cytoskeleton , immunology , rna , cell , splenectomy , spleen
We studied a family with autosomal dominant hereditary spherocytosis (HS) associated with a mild spectrin deficiency. Linkage analysis using two microsatellite markers (D14S63 and D14S271) very close to the β‐spectrin gene (SPTB) showed that HS co‐segregated with alleles of these microsatellite markers and the linkage between the marker and HS was statistically significant. The presence of a β‐spectrin protein polymorphism (β‐spectrin Vay; A1880V) in trans of the HS allele was not itself deleterious, but allowed the detection of decreased membrane expression of the spherocytic β‐spectrin allele in two HS‐affected subjects. Direct sequencing of the coding exons of the β‐spectrin gene in one affected subject showed the presence of a G → C transversion at the terminal nucleotide of exon 3, which did not change the leucine codon 100 (CTG → CTC). The presence of the mutation was confirmed by restriction enzyme digestion at the DNA level in all affected SH members of the family. The G → C mutation severely reduced the utilization of the 5′ splice site and resulted in aberrant mRNA splicing with intron 3 retention.