TABLE I.   Point Mutations and Frameshifts Causing (Silent) Beta-Thalassemia (numbers counted from the Cap site; see also Fig. 2).

Mutation Type Ethnic Group Mutation Type Ethnic Group

A.   Transcriptional Mutants (n=22)
-101, C->T beta+ Turkish; Bulgarian; Italian -31, A->C beta+ Italian
-92, C->T beta+ Mediterranean -31, A->G beta+ Japanese
-90, C->T beta+ Portuguese -30, T->A beta+ Turkish; Macedonian; Bulgarian
-88, C->A beta+ Kurds -30, T->C beta+ Chinese
-88, C->T beta+ Black populations -29, A->G beta+ American Blacks; Chinese
-87, C->A beta+ American Blacks -28, A->C beta+ Kurds
-87, C->G beta+ Mediterranean -28, A->G beta+ Chinese
-87, C->T beta+ German/Italian +10, -T beta+ Greek
-86, C->A beta+ Italian +22, G->A beta+ Turkish; Bulgarian; Italians
-86, C->G beta+ Lebanese; Thai +33. C->G beta+ Greek Cypriots
-32, C->A beta+ Taiwanese +43 to +40, -AAAC beta+ Chinese

The locations of these 20 mutations and two deletions are also shown in Fig. 1; most are located in the CACCC and ATAAAA boxes.

Mutation Type Ethnic Groups

B-a.   RNA Processing Mutants: Mutations in Splice Junctions (n=22)
IVS-I (-3), C->T (codon 29; Gly->Gly) beta+ Lebanese
IVS-I (-2), A->G (codon 30; Arg->Gly) beta° Sephardic Jews
IVS-I (-1), G->A (codon 30; Arg->Lys) beta° Bulgarian
IVS-I (-1), G->C (codon 30; Arg->Thr) beta° American Blacks; Tunisians; UAE; Indian
IVS-I-1, G->A beta° Mediterranean; Asian Indian
IVS-I-1, G->T beta° Asian Indian
IVS-II-1, G->A beta° Mediterranean; Tunisian; American Blacks
IVS-II-1, G->C beta° Iranian
IVS-I-2, T->A beta° Algerian
IVS-I-2, T->C beta° American Blacks
IVS-I-2, T->G beta° Tunisian
IVS-II-2,3, +11 bp, -2 bp beta° Iranian
IVS-I, -17 nts (3' end) beta° Kuwaiti
IVS-I-130, G->A beta° Egyptian
IVS-I-130, G->C beta° Turkish; Japanese
Codon 30, G->C [IVS-I-130 (+1)] beta° Middle East
IVS-II-849, A->C beta° American Blacks
IVS-II-849, A->G beta° American Blacks
IVS-II-850, -G beta° Italian
IVS-II-850, G->A beta° English-Scottish
IVS-II-850, G->C beta° Yugoslavian
IVS-II-850, G->T beta° Japanese

B-b.   RNA Processing Mutants: Mutations in the Consensus Sites (n=12)
IVS-I-5, G->A beta+ Algerian; Mediterranean
IVS-I-5, G->C beta+ Asian Indian; Chinese; Melanesian
IVS-I-5, G->T beta+ Mediterranean; American Blacks
IVS-II-4,5, -AG beta°? Portuguese
IVS-II-5, G->C beta+ Chinese
IVS-I-6, T->C beta+ Mediterranean
IVS-I-128, T->G beta+ Saudi Arabian
IVS-II-837, T->G ? Asian Indian
IVS-II-843, T->G beta+ Algerian
IVS-II-844, C->G beta+ Italian
IVS-II-848, C->A beta+ American Blacks; Egyptian; Iranian
IVS-II-848, C->G beta+ Japanese

B-c.   RNA Processing Mutants: Changes in IVS-I or IVS-II (n=5)
IVS-I-110, G->A beta+ Mediterranean
IVS-I-116, T->G beta° Mediterranean
IVS-II-654, C->T beta+ Chinese
IVS-II-705, T->G beta+ Mediterranean
IVS-II-745, C->G beta+ Mediterranean

B-d.   RNA Processing Mutants: Changes in Coding Regions (n=5)
Codon 10, C->A (Ala->Ala) beta+ Asian Indian
Codon 19, A->G (Hb Malay; Asn->Ser) beta+ Malay
Codon 24, T->A (Gly->Gly) beta+ American Blacks; Japanese
Codon 26, G->A (Hb E; Glu->Lys) beta+ Southeast Asian
Codon 27, G->T (Hb Knossos; Ala->Ser) beta+ Mediterranean

C-a.   RNA Translation Mutants: Nonsense Mutations (n=12)
Codon 15, TGG->TAG beta° Asian Indian; Turkish
Codon 15, TGG->TGA beta° Portuguese
Codon 17, A->T beta° Chinese
Codon 22, G->T beta° Reunion Islanders
Codon 26, G->T beta° Thai
Codon 35, C->A beta° Thai
Codon 37, G->A beta° Saudi Arabian; Spanish
Codon 39, C->T beta° Mediterranean
Codon 43, G->T beta° Chinese
Codon 61, A->T beta° Blacks
Codon 90, G->T beta° Japanese
Codon 112, T->A beta° Slovakian

C-b.   RNA Translation Mutants: Frameshift Mutations (n=55)
Codon 1, -G beta° Mediterranean
Codons 2/3/4, -9 bp; +31 bp beta° Algerian
Codon 5, -CT beta° Mediterranean
Codon 6, -A beta° Mediterranean; American Blacks
Codon 8, -AA beta° Mediterranean
Codons 8/9, +G beta° Asian Indian
Codons 9/10, +T beta° Greek
Codon 11, -T beta° Mexican
Codons 14/15, +G beta° Chinese
Codon 15, -T beta° Malay
Codon 16, -C beta° Asian Indian
Codons 22/23/24, -AAGTTGG beta° Turkish
Codon 24, -G; +CAC beta° Egyptian
Codons 25/26, +T beta° Tunisian
Codon 26, +T beta° Japanese
Codons 27/28, +C beta° Chinese
Codon 28, -C beta° Egyptian
Codons 28/29, -G beta° Japanese; Egyptian
Codon 31, -C beta° Chinese
Codon 35, -C beta° Malay
Codons 36/37, -T beta° Iranian; Kurds
Codons 37/38/39, -GACCCAG beta° Turkish
Codons 38/39, -C beta° Czech
Codons 38/39, -CC beta° Belgians
Codon 40, -G beta° Japanese
Codons 40/41, +T beta° Chinese
Codon 41, -C beta° Thai
Codons 41/42, -TTCT beta° Chinese
Codons 42/43, +G beta° Japanese
Codons 42/43, +T beta° Japanese
Codon 44, -C beta° Kurds
Codon 45, -T beta° United Arab Emirates
Codon 47, +A beta° Surinamese
Codons 47/48, +ATCT beta° Punjabi
Codon 51, -C beta° Hungarian
Codons 53/54, +G beta° Japanese
Codon 54, -T beta° Algerian; Swedish
Codons 54/55, +A beta° Indian
Codons 56-60, +14 bp beta°  
Codons 57/58, +C beta° Punjabi
Codon 59, -A beta° Italian
Codon 64, -G beta° Swiss
Codon 67, -TG beta° Filipino
Codons 71/72, +A beta° Chinese
Codons 71/72, +T beta° Chinese
Codons 72/73, -AGTGA; +T beta° British
Codons 74/75, -C beta° Turkish
Codon 76, -C beta° Italian
Codons 82/83, -G beta° Azerbaijani; Czech; Croatian
Codons 84/85, +C beta° Japanese
Codons 84/85/86, +T beta° Japanese
Codon 88, +T beta° Asian Indian
Codons 89/90, -GT beta° Korean
Codon 95, +A beta° Thai
Codons 106/107, +G beta° American Blacks

D.   Dominant Beta-Thal and Highly Unstable Beta Chain Variants (n=30)
Codons 24/25, -GGT beta° Japanese
Codon 28, CTG->CGG beta° (Hb Chesterfield)
Codons 31/32, +CGG beta° Spanish
Codon 32, CTG->CAG (Leu->Gln);
Codon 98, GTG->ATG (Val->Met)
beta° (Hb Medicine Lake)
Codons 33/34, -GTG beta° (Hb Korea) Koreans
Codon 60, GTG->GAG (Val->Glu) beta° (Hb Cagliari) Italians
Codon 94, +TG beta° (Hb Agnana) Italian
Codon 100, -CTT, +TCTGAGAACTT beta° South African
Codons 108/109/110/111/112, -12 bp beta° Swedish
Codon 109, -G beta° (Hb Manhattan) Ashkenazi Jews
Codon 110, T->C beta° (Hb Showa-Yakushiji) Japanese
Codon 114, -CT; +G beta° (Hb Geneva) French Swiss
Codon 114, T->C beta° (Hb Durham-N.C.; Hb Brescia) Italians
Codon 115, C->A beta° [Hb Hradec Kralove (Hb HK)] Czech
Codons 120/121, +A beta° Filipino
Codon 121, G->T beta° Polish; Swiss; Japanese; English; Czech
Codon 123, -A beta° (Hb Makabe) Japanese
Codons 123/124/125, -ACCCCACC beta° Thai
Codon 124, -A beta° Russian
Codon 124/125/126, +CCA beta° Russian
Codon 125, -A beta° Japanese
Codon 126, -T beta° (Hb Vercelli) Italian
Codon 126, GTG->GGG beta° (Hb Neapolis) Italians; German; Thai
Codons 126/127/128/129/130/131, -17 bp beta° Pakistani
Codon 127, CAG->TAG (Gln->stop codon) beta° English
Codon 127, CAG->CCG (Gln->Pro) beta° (Hb Houston) British
Codon 127, CAG->CGG (Gln->Arg) beta° French
Codons 127/128, -AGG (Gln·Ala->Pro) beta° (Hb Gunma) Japanese
Codons 128/129, -4 bp, +5 bp and Codons 132/133/134/135, -11 bp beta° Irish
Codons 134/135/136/137, -10 bp, +4 bp beta° Portuguese

E.   Cap Site Mutations (n=1)
Cap +1, A->C beta+ Asian Indian

F.   Initiation Codon Mutations (n=6)
ATG->GTG beta° Japanese
ATG->ACG beta° Yugoslavian
ATG->AGG beta° Chinese; Korean; North European
ATG->ATA beta° Italian; Swedish
ATG->ATC beta° Japanese
ATG->ATT beta° Iranian

G.   3'UTR Mutations (n=3)
3'UTR +6, +1,480; C->G beta+ Greek (also known as +6, C->G)
3'UTR +1,565 to +1,577; -13 bp beta+? Turkish
3'UTR +1,570; T->C beta+? Irish

H.   Mutations in the Polyadenylation Site (poly A) (n=6)
AATAAA->AACAAA beta+ American Blacks
AATAAA->AATGAA beta+ Mediterranean
AATAAA->AATAGA beta+ Malay
AATAAA->AATAAG beta+ Kurds
AATAAA->AAAA (-AT or -TA) beta+ French
AATAAA->A (-AATAA) beta+ Arabian

This material is from the book A Syllabus of Thalassemia Mutations (1997) by Titus H.J. Huisman, Marianne F.H. Carver, and Erol Baysal, published by The Sickle Cell Anemia Foundation in Augusta, GA, USA. Copyright © 1997 by Titus H.J. Huisman. All rights reserved. Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, microfilming and recording, or by any information storage and retrieval systems, without permission in writing from the Author.