C-Terminal Deletions in the ALAS2 Gene Lead to Gain of Function and Cause X-linked Dominant Protoporphyria without Anemia or Iron Overload

American Journal of Human Genetics

Volumn 83, Issue 3, 2008, Pages 408-414

  Whatley, Sharon D ^a   Ducamp, Sarah ^b,c   Gouya, Laurent ^b,c   Grandchamp, Bernard ^c,d   Beaumont, Carole ^c   Badminton, Michael N ^a   Elder, George H ^a   Holme, S Alexander ^a   Anstey, Alexander V ^a   Parker, Michelle ^e   Corrigall, Anne V ^e   Meissner, Peter N ^e   Hift, Richard J ^e   Marsden, Joanne T ^f   Ma, Yun ^f   Mieli Vergani, Giorgina ^f   Deybach, Jean Charles ^b,c   Puy, Hervé ^b,c  

^a UNIVERSITY HOSPITAL OF WALES   (United Kingdom)

^b HÔPITAL LOUIS MOURIER   (France)

^c CENTRE DE RECHERCHE BIOMÉDICALE BICHAT BEAUJON CRB3   (France)

^d BICHAT HOSPITAL   (France)

^e UNIVERSITY OF CAPE TOWN   (South Africa)

^f KING S COLLEGE HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINOLEVULINATE SYNTHASE; GENOMIC DNA;

ALAS2 GENE; ANEMIA; ARTICLE; CARBOXY TERMINAL SEQUENCE; CHILD PARENT RELATION; ERYTHROPOIETIC PROTOPORPHYRIA; FAMILY STUDY; FEMALE; GENE; GENE DELETION; HUMAN; HUMAN TISSUE; IRON OVERLOAD; MAJOR CLINICAL STUDY; MALE; NUCLEOTIDE SEQUENCE; PEDIGREE; PHYLOGENETIC TREE; PRIORITY JOURNAL; SEQUENCE ALIGNMENT; X CHROMOSOME LINKED DISORDER;

5-AMINOLEVULINATE SYNTHETASE; CHROMOSOMES, HUMAN, X; ERYTHROCYTES; FEMALE; HEME; HUMANS; MALE; MUTATION; PORPHYRIAS, HEPATIC; PROTOPORPHYRINS;

PROKARYOTA;

EID: 51149108520     PISSN: 00029297     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ajhg.2008.08.003     Document Type: Article

References (23)

1. Sassa S. Modern diagnosis and management of the porphyrias. Br. J. Haematol. 135 (2006) 281-292
2. Bottomley S.S. Sideroblastic anemias. In: Lukens J.N., Rogers G.M., Paraskevas F., and Glader B.E. (Eds). Wintrobe's Clinical Hematology, J.P. Greer J. Foerster (2004), Lippincott Williams & Wilkins, Philadelphia 1012-1033
3. Cox T.M. Erythropoietic protoporphyria. In: Kadish K.M., Smith K.M., and Guilard R. (Eds). The Porphyrin Handbook, Vol 14, Medical aspects of porphyrias (2003), Academic Press, Amsterdam 121-150
4. Gouya L., Martin-Schmitt C., Robreau A.M., Austerlitz F., Da Silva V., Brun P., Simonin S., Lyoumi S., Grandchamp B., Beaumont C., et al. Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria. Am. J. Hum. Genet. 78 (2006) 2-14
5. Whatley S.D., Mason N.G., Holme S.A., Anstey A.V., Elder G.H., and Badminton M.N. Gene dosage analysis identifies large deletions of the FECH gene in 10% of UK families with erythropoietic protoporphyria. J. Invest. Dermatol. 127 (2007) 2790-2794
6. Holme S.A., Anstey A.V., Finlay A.Y., Elder G.H., and Badminton M.N. Erythropoietic protoporphyria in the U.K.: Clinical features and effect on quality of life. Br. J. Dermatol. 155 (2006) 574-581
7. Parker M., Corrigall A.V., Hift R.J., and Meissner P.N. Molecular characterisation of erythropoietic protoporphyria in South Africa. Br. J. Dermatol. 159 (2008) 182-191
8. Deacon A.C., and Elder G.H. Front line tests for the investigation of suspected porphyria. J. Clin. Pathol. 54 (2001) 500-507
9. Hart D., and Piomelli S. Simultaneous quantitation of zinc protoporphyrin and free protoporphyrin in erythrocytes by acetone extraction. Clin. Chem. 27 (1981) 220-222
10. Tovey J.A., and Elder G.H. Ferrochelatase activity in human lymphocytes: Effect of storage on haem formation. Ann. Clin. Biochem. 27 (1990) 80-81
11. Went L.N., and Klasen E.C. Genetic aspects of erythropoietic protoporphyria. Ann. Hum. Genet. 48 (1984) 105-117
12. Cox T.C., Sadlon T.J., Schwarz Q.P., Matthews C.S., Wise P.D., Cox L.L., Bottomley S.S., and May B.K. The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis. Int. J. Biochem. Cell Biol. 36 (2004) 281-295
13. Harigae H., Furuyama K., Kimura A., Neriishi K., Tahara N., Kondo M., Hayashi N., Yamamoto M., Sassa S., and Sasaki T. A novel mutation of the erythroid-specific delta-aminolaevulinate synthase gene in a patient with X-linked sideroblastic anaemia. Br. J. Haematol. 106 (1999) 175-177
14. Holme S.A., Worwood M., Anstey A.V., Elder G.H., and Badminton M.N. Erythropoiesis and iron metabolism in dominant erythropoietic protoporphyria. Blood 110 (2007) 4108-4110
15. Lyoumi S., Abitbol M., Andrieu V., Henin D., Robert E., Schmitt C., Gouya L., de Verneuil H., Deybach J.C., Montagutelli X., et al. Increased plasma transferrin, altered body iron distribution and microcytic hypochromic anemia in ferrochelatase deficient mice. Blood 109 (2007) 811-818
16. Cotter P.D., Rucknagel D.L., and Bishop D.F. X-linked sideroblastic anemia: Identification of the mutation in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) in the original family described by Cooley. Blood 84 (1994) 3915-3924
17. Keel S.B., Doty R.T., Yang Z., Quigley J.G., Chen J., Knoblaugh S., Kingsley P.D., De Domenico I., Vaughn M.B., Kaplan J., et al. A heme export protein is required for red blood cell differentiation and iron homeostasis. Science 319 (2008) 825-828
18. Cooperman S.S., Meyron-Holtz E.G., Olivierre-Wilson H., Ghosh M.C., McConnell J.P., and Rouault T.A. Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. Blood 106 (2005) 1084-1089
19. Labbé R.F., and Rettmer R.L. Zinc protoporphyrin: A product of iron-deficient erythropoiesis. Semin. Hematol. 26 (1989) 40-46
20. Schranzhofer M., Schrifrer M., Cabrera J.A., Kopp K., Chiba P., Beug H., and Mullner E.W. Remodelling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis. Blood 107 (2006) 4159-4167
21. Ishikawa H., Kato M., Hori H., Ishimori K., Kirisako T., Tokunaga F., and Iwai K. Involvement of heme regulatory motif in heme-mediated ubiquitinisation and degradation of IRP2. Mol. Cell 19 (2005) 171-181
22. Astner I., Schulze J.O., van den Heuvel J., Jahn D., Schubert W.D., and Heinz D.W. Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans. EMBO J. 24 (2005) 3166-3177
23. Eales L., Day R.S., and Pimstone N.R. Protoporphyrin (proto)-determined hepatopathty in a South African Jewish family. Ann. Clin. Res. 10 (1978) 205-213