Splice junction mutations

Rl. Raben, N., Sherman, J., Miller, E, Mena, H., and Plotz, P., A5 splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease). J. Biol. Chem. 268,4963-4967 (1993). 

T24. Tsujino, S., Tonin, P Shanske, S., Nohria, V., Boustany, R.-M., Lewis, D Chen, Y.-T., and DiMauro, S., A splice junction mutation in a new myopathic variant of phosphoglycerate kinase deficiency (PGK North Carolina). Ann. Neurol. 35,349-353 (1994). 

Otterness DM, Szumlanski CL, Wood TC et al. Human thiopurine methyltransferase pharmacogenetics. Kindred with a terminal exon splice junction mutation that results in loss of activity. J Clin Invest 1998 101 1036-1044. 

Over 250 mutations have been reported in GBA 203 missense mutations, 18 nonsense mutations, 36 small insertions or deletions that lead to either frameshifts or in-frame alterations, 14 splice junction mutations, and 13 complex alleles carrying two or more mutations in cis (Hruska et al., 2008). Recombination events with a... 

Eeitersdorf E, Reshef A, Meiner V, Eevitzki R, Schwartz SP, Dann EJ, Berkman N, Cali JJ, Kla-pholz E, Berginer VM (1993) Erameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews of Moroccan origin. J Clin Invest 91 2488-2496... 

Myerowitz, R., 1988, Splice junction mutation in some Ashkenazi Jews with Tay-Sachs disease Evidence against a single defect within this ethnic group, Proc. Natl. Acad. Sci. USA 85 3955-3958. 

Shimmoto, M., Takano, T., Fukuhara, Y., Oshima, A., Sakuraba, H., and Suzuki, Y., 1990, Japanese-type adult galactosialidosis A unique and common splice junction mutation causing exon skipping in the protective protein/carboxypeptidase gene, Proc. Jpn. Acad. 66B 217-222. 

Leitersdorf, E., Reshef, A., Meiner, V., Levitzki, R., Schwartz, S. P., Dann, E. J., Berkman, N., Cali, J. J., Klapholz, L. and Berginer, V. M. (1993). Frameshift and splice-j-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomathosis in Jews of Moroccan origin., /. Clin. Invest. 91 2488-2496. 

Molecular genetics Impaired production of P-globin peptide chain. Numerous mutations have been identified in the production of ribonucleic acid (RNA) including in the promoter region and splice junctions. 

Be familiar with common mutations that cause thalassemias (substitutions in TATA box, mutations in splice junction, and changes in stop codon). 

Some types of -thalassemia (little or none of the hemoglobin p chain produced) are caused by homozygous mutations in the splice junction sequences at intron/exon boundaries. In some individuals, an AT replaces a GT in the gene at the 5 end of the first or second intron. Mutations also occur within the splice junction sequences at the 3 -end of introns (GT at the donor site 5 -end and AG at the acceptor site 3 -end). Mutations at either site totally abolish normal splicing and result in p thalassemia. 

D.N. (1992) The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes causes and consequences. Hum. Genet., 90 (1-2), 41-54. 

Ohno, K., and Suzuki, K., 1988b, A splicing defect due to an exon-intron junctional mutation results in abnormal P-hexosaminidase a chain mRNAs in Ashkenazi Jewish patients with Tay-Sachs disease, Biochem. Biophys. Res. Commun. 153 463-469. 

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