ABCG8 p.Gln271*
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[hide] Stomatocytic haemolysis and macrothrombocytopenia ... Br J Haematol. 2005 Jul;130(2):297-309. Rees DC, Iolascon A, Carella M, O'marcaigh AS, Kendra JR, Jowitt SN, Wales JK, Vora A, Makris M, Manning N, Nicolaou A, Fisher J, Mann A, Machin SJ, Clayton PT, Gasparini P, Stewart GW
Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia.
Br J Haematol. 2005 Jul;130(2):297-309., [PMID:16029460]
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Phytosterolaemia (sitosterolaemia) is a recessively inherited metabolic condition in which the absorption of both cholesterol and plant-derived cholesterol-like molecules at the gut is unselective and unrestricted. In haematology, Mediterranean stomatocytosis or Mediterranean macrothrombocytopenia is a poorly understood haematological condition that combines stomatocytic haemolysis with the presence of very large platelets. Five pedigrees showing this haematology were identified. Gas chromatography mass spectrometry (GC-MS) showed that all of the patients with this highly specific haematology had grossly elevated levels of phytosterols in the blood, diagnostic of phytosterolaemia. All showed mutations in the ABCG5 and ABCG8 previously linked to phytosterolaemia. Three pedigrees showed five new mutations, while two pedigrees showed the common W361X mutation in ABCG8. We draw the following four conclusions: (i) that Mediterranean stomatocytosis/macrothrombocytopenia is caused by an excess of phytosterols in the blood; (ii) that phytosterolaemia, which does not respond to standard statin treatment, can be diagnosed via the distinctive haematology described here, even when the cholesterol is normal; (iii) that phytosterolaemia should be considered in the differential diagnosis of all patients with large platelets; and (iv) that the platelet size should be noted in patients with hypercholesterolaemia.
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No. Sentence Comment
174 Family Sitosterol level (lmol/l) ABCG5 ABCG8 A E77X (229G>T) A-I-2 44 m/n A-II-1 1471 m/m A-II-2 17 n/n A-II-3 57 n/n A-II-4 970 m/m A-II-5 625 m/m A-II-9 508 m/m B IVS11+3insT R50C (148C>T) E146X (436G>T), M622V (1864A>G) B-I-1 77 n/n m/n B-I-2 42 m/n n/n B-II-1 2230 m/n m/n B-II-2 2350 m/n m/n B-II-3 137 n/n m/n C Q604E (1810C>G) Q271X (811C>T) IV9-3insT IV8-1G/A C54Y (161G>A) C-I-1 114 m/n n/n m/n m/n C-I-2 29 m/m m/n n/n m/m C-II-1 2100 m/n m/n m/n m/n C-II-2 2580 m/n m/n m/n m/n D W361X (1083G>A) D-I-1 22 m/n D-II-1 715 m/m E W361X (1083G>A) E-I-1 23 m/n E-II-1 1844 m/m E-II-2 21 n/n Mutations are shown in bold and large font.
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ABCG8 p.Gln271* 16029460:174:334
status: VERIFIED131 Affected siblings in family C were compound heterozygous for Q271X and IV8-1G>A, which are both novel, while both affected individuals in families D and E were homozygous for the previously described W361X mutation in ABCG8, which is the single commonest mutation in phytosterolaemia (Berge et al, 2000; Lee et al, 2001b; Lu et al, 2001).
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ABCG8 p.Gln271* 16029460:131:61
status: VERIFIED