A mutation screen of the TSC1 gene reveals 26 protein truncating mutations and 1 splice site mutation in a panel of 79 tuberous sclerosis patients

Annals of Human Genetics

Volumn 62, Issue 3, 1998, Pages 203-213

  Young, J M ^a   Burley, M W ^a   Jeremiah, S J ^a   Jeganathan, D ^a   Ekong, R ^a   Osborne, J P ^b   Povey, S ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b ROYAL UNITED HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

MUTANT PROTEIN;

ARTICLE; CONTROLLED STUDY; FEMALE; FIBROMA; GENE MUTATION; HUMAN; HUMAN CELL; MALE; MUTATION RATE; PRIORITY JOURNAL; RNA SPLICING; TUBEROUS SCLEROSIS;

BLOTTING, SOUTHERN; CHROMOSOMES, HUMAN, PAIR 9; FEMALE; GENE REARRANGEMENT; HAPLOTYPES; HUMANS; MALE; MUTATION; NUCLEIC ACID HETERODUPLEXES; PEDIGREE; POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL; PROTEINS; RNA SPLICING; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR PROTEINS;

EID: 0031697622     PISSN: 00034800     EISSN: None     Source Type: Journal    
DOI: 10.1017/S0003480098006861     Document Type: Article

References (35)

1. AU, K.-S., RODRIGUEZ, J., RODRIGUEZ JR, E., DOBYNS, W., DELGADO, M. & NORTHRUP, H. (1997). Mutations and polymorphisms in the tuberous sclerosis complex gene on chromosome 16. Hum. Mutat. 9, 23-29.
2. BROOK-CARTER, P., PERAL, B., WARD, C., THOMPSON, P., HUGHES, J., MAHESHWAR, M., NELLIST, M., GAMBLE, V., HARRIS, P. & SAMPSON, J. (1994). Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease - a contiguous gene syndrome. Nature Genet. 8, 328-332.
3. CARBONARA, C., LONGA, L., GROSSO, E., BORRONE, C., GARRE, M., BRISIGOTTI, M. & MIGONE, N. (1994). 9q34 loss of heterozygosity in a tuberous sclerosis astro-cytoma suggests a growth suppressor-like activity also for the TSC1 gene. Hum. Mol. Genet. 3, 1829-1832.
4. COOPER, D. & YOUSSOUFIAN, H. (1988). The CpG dinucleotide and human genetic disease. Hum. Genet. 78, 151-155.
5. FRYER, A., CONNOR, J., POVEY, S., YATES, J., CHALMERS, A., FRASER, I., YATES, A. & OSBORNE, J. (1987). Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet 1, 659-661.
6. GOMEZ, M. ed. (1988). Tuberous sclerosis, second edition. New York: Raven Press.
7. GOMEZ, M. (1991). Phenotypes of the Tuberous Sclerosis Complex with a revision of diagnostic criteria. Ann. N.Y. Acad. Sci. 615, 1-7.
8. GREEN, A., JOHNSON, P. & YATES, J. (1994a). The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor. Hum. Mol. Genet. 3, 1833-1834.
9. GREEN, A., SMITH, M. & YATES, J. (1994b). Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients. Nature Genet. 6. 193-196.
10. GUNTHER, M. & PENROSE, L. (1935). The genetics of epiloia. J. Genet. 31, 413-430.
11. HENSKE, E., SCHEITHAUER, B., SHORT, M., WOLLMANN, R., NAHMIAS, J., HORNIGOLD, N., VAN SLEGTENHORST, M., WELSH, C. & KWIATKOSWKI, D. (1996). Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. Am. J. Hum. Genet. 59, 400-406.
12. JONES, A., DANIELLS, C., SNELL, R., TACHATAKI, M., IDZIASZCZYK, S., KRAWCZAK, M., SAMPSON, J. & CHEADLE, J. (1997). Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis. Hum. Mol. Genet. 6, 2155-2161.
13. KANDT, R., HAINES, J., SMITH, M., NORTHRUP, H., GARDNER, R., SHORT, M., DUMARS, K., ROACH, E., STEINGOLD, S., WALL, S., BLANTON, S., FLODMAN, P., KWIATKOWSKI, D., JEWELL, A., WEBER, J., ROSES, A. & PERICAK-VANCE, M. (1992). Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nature Genet. 2, 37-41.
14. KUMAR, A., KANDT, R., WOLPERT, C., ROSES, A., PERICAK-VANCE, M. & GILBERT, J. (1995a). Mutation analysis of the TSC2 gene in an African-American family Hum. Mol. Genet. 4, 2295-2298.
15. KUMAR, A., KANDT, R., WOLPERT, C., ROSES, A., PERICAK-VANCE, M. & GILBERT, J. (1997). A novel splice site mutation (156+1G → A) in the TSC2 gene. Hum. Mutat. 9, 64-65.
16. KUMAR, A., WOLPERT, C., KANDT, R., SEGAL, J., PUFKY, J., ROSES, A., PERICAK-VANCE, M. & GILBERT, J. (1995b). A de novo frame-shift mutation in the tuberin gene Hum. Mol. Genet. 4, 1471-1472.
17. MAHESHWAR, M., CHEADLE, J., JONES, A., MYRING, J., FRYER, A., HARRIS, P. & SAMPSON, J. (1997). The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis. Hum. Mol. Genet. 6, 1991-1996.
18. NELLIST, M., JANSSEN, B., BROOKCARTER, P., HESSELLING-JANSSEN, A., MAHESHWAR, M., VERHOEF, S., VAN DEN OUWELAND, A., LINDHOUT, D., EUSSEN, B., CORDEIRO, I., SANTOS, H., HALLEY, D. & SAMPSON, J. (1993). Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75, 1305-1315.
19. NORTHRUP, H., WHELESS, J., BERTIN, T. & LEWIS, R. (1993). Variability of expression in tuberous sclerosis. J. Med. Genet. 30, 41-43.
20. OSBORNE, J. (1988). Diagnosis of tuberous sclerosis. Arch. Dis. Child. 63, 1423-1425.
21. OSBORNE, J., FRYER, A. & WEBB, D. (1991). Epidemiology of tuberous sclerosis. Ann. N.Y. Acad. Sci 615, 125-127.
22. POVEY, S., BURLEY, M., ATTWOOD, J., BENHAM, F., HUNT, D., JEREMIAH, S., FRANKLIN, D., GILLETT, G., MALAS, S., ROBSON, E., TIPPETT, P., EDWARDS, J., KWIATKOWSKI, D., SUPER, M., MUELLER, R., FRYER, A., CLARKE, A., WEBB, D. & OSBORNE, J. (1994). Two loci for tuberous sclerosis: one on 9q34 and one on 16p13. Ann. Hum. Genet. 58, 107-127.
23. SAMPSON, J., SCAHILL, S., STEPHENSON, J., MANN, L. & CONNOR, J. (1989). Genetic aspects of tuberous sclerosis in the west of Scotland. J. Med. Genet. 26, 28-31.
24. SAMPSON, J., MAHESHWAR, M., ASPINWALL, R., THOMPSON, P., CHEADLE, J., RAVINE, D., ROY, S., HAAN, E., BERNSTEIN, J. & HARRIS, P. (1997). Renal cystic kidney disease in tuberous sclerosis: role of the polycystic kidney disease 1 gene. Am. J. Hum. Genet. 61, 843-851.
25. SEPP, T., YATES, J. & GREEN, A. (1996). Loss of heterozygosity in tuberous sclerosis hamartomas. J. Med. Genet. 33, 962-964.
26. SMALLEY, S., BURGER, F. & SMITH, M. (1994). Phenotypic variation of tuberous sclerosis in a single extended kindred. J. Med. Genet. 31, 761-765.
27. VAN BAKEL, I., SEPP, T., WARD, S., YATES, J. & GREEN, A. (1997). Mutations in the TSC2 gene: analysis of the complete coding sequence using the protein truncation test (PTT). Hum. Mol. Genet. 6, 1409-1414.
28. VAN SLEGTENHORST, M., DE HOOGT, R., HERMANS, C., NELLIST, M., JANSSEN, B., VERHOEF, S., LINDHOUT, D., VAN DEN OUWELAND, A., HALLEY, D., YOUNG, J., BURLEY, M.-W., JEREMIAH, S., WOODWARD, K., NAHMIAS, J., FOX, M., EKONG, R., OSBORNE, J., WOLFE, J., POVEY, S., SNELL, R., CHEADLE, J., JONES, A., TACHATAKI, M., RAVINE, D., SAMPSON, J., REEVE, M., RICHARDSON, P., WILMER, F., MUNRO, C., HAWKINS, T., SEPP, T., ALI, J., WARD, S., GREEN, A., YATES, J., KWIATKOWSKA, J., HENSKE, E., SHORT, M., HAINES, J., JOZWIAK, S. & KWIATKOWSKI, D. (1997). Identification of the tuberous Sclerosis gene TSC1 on chromosome 9q34. Science 277, 805-808.
29. VRTEL, R., VERHOEF, S., BOUMAN, K., MAHESHWAR, M., NELLIST, M., VAN ESSEN, A., BAKKER, P., HERMANS, C., BINK-BOELKENS, M., VAN ELBURG, R., HOFF, M., LINDHOUT, D., SAMPSON, J., HALLEY, D. & VAN DEN OUWELAND, A. (1996). Identification of a nonsense mutation at the 5′ end of the TSC2 gene in a family with a presumptive diagnosis of tuberous sclerosis complex. J. Med. Genet. 33, 47-51.
30. WEBB, D. & OSBORNE, J. (1991). Non-penetrance in tuberous sclerosis. J. Med. Genet. 28, 417-419.
31. WEBB, D., FRYER, A. & OSBORNE, J. (1991). On the incidence of fits and mental retardation in tuberous sclerosis. J. Med. Genet. 28, 395-397.
32. WEBB, D., FRYER, A., & OSBORNE, J. (1996). Morbidity associated with tuberous sclerosis: a population study. Dev. Med. Child. Neurol. 38, 146-155.
33. WIENECKE, R., KONIG, A. & DECLUE, J. (1995). Identification of tuberin, the tuberous sclerosis-2 product tuberin. Possesses specific Rap1GAP activity. J. Biol. Chem. 270, 16409-16414.
34. WILSON, P., RAMESH, V., KRISTIANSEN, A., BOVE, C., JOZWIAK, S., KWIATKOWSKI, D., SHORT, M. & HAINES, J. (1996). Novel mutations detected in the TSC2 gene from both sporadic and familial TSC patients. Hum. Mol. Genet. 5, 249-256.
35. XIAO, G.-H., SHOARINEJAD, F., JIN, F., GOLEMIS, E. & YEUNG, R. (1997). The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J. Biol. Chem. 272, 6097-6100.