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 |