The spectrum of beta-thalassemia mutations in the 22 Arab countries: a systematic review

Figures & data

Figure 1. Flow diagram of the process for study selection. ^aFor the Google Scholar search, only the most relevant records were retained, as n = 44,217 for the total-identified records

Table 1. Beta-thalassemia HBB gene mutations unique to Arabs

HGVS name	Common name	Type of mutation	Origin	Arab country	Number of patients/alleles/chromosomes with the mutation	Clinical phenotype as reported in the original article	Reference
c.92 + 2 T > G	IVS I-2 (T > G)	Splice junction	Tunisian	Tunisia	14 chromosomes	β -thal major	[71]
				Morocco	12 chromosomes	β -thal major	[65,67]
c.-240 G > A	−190 (G > A)	Promoter	Moroccan	Morocco	2 chromosomes	β – thal intermedia	[65]
c.150delC	CD 49 (−C)	Frameshift	Jordanian	Jordan	1 patient	β -thal major	[63]
c.420dupT	CD 139/140 + T [163 aa]	Frameshift	Kuwaiti	Kuwait	1 patient	β -thal major	[59]
Not available	Deletion spans exon 1, the entire intron 1 and the first two bases of exon 2	Deletion, Frameshift	Qatari	Qatar	1 allele	β -thal major	[60]
Not available	Deletion of 9.6 kb extending from exon 1 of δ-globin gene to IVS-II sequence of β-globin gene	Deletion	Sudanese	Sudan	1 patient	δ β-thal carriers, hereditary persistence of fetal hemoglobin	[64]

Abbreviations: HGVS: Human Genome Variation Society; β -thal: Beta-thalassemia.

Table 2. Beta-thalassemia common mutations in the HBB gene among Arab countries shared with other ethnic groups

HGVS name	Common name	Type of mutation	Origin(s)	Arab country	Number of patients/alleles/chromosomes with the mutation*		Clinical phenotype(s) as reported in the original article(s)	Reference(s)	Other ethnic group(s)	Clinical phenotype	Reference(s)
C.92 + 5 G > C	IVSI-5(G > C)	Splice site	Asian Indian, SE Asian, Melanesian, Pakistani	Saudi Arabia	131patients		β -thal major, HbA2 > 3%, β -thal	[18,19,55,58,77,83]	Mauritius, Maldives	β + -thal	[73]
				Oman	187 chromosomes		β -thal	[20,21]
				The United Arab Emirates	367 chromosomes, 163 patients		β -thal	[22,79]
				Palestinian territories	5 alleles		β -thal transfusion dependent & β -thal carrier, β -thal	[23,76]
				Syria	60 alleles, 15 patients		β -thal, β -thal major & β -thal carrier	[48,54]
				Tunisia	5 chromosomes		β -thal major, β -thal carrier, HbS/b-thal, Hb C/b-thal, O-Arab/b-thal	[71]
				Bahrain	39 patients		β -thal major & β -thal carrier, β -thal and sickle cell	[24,25]
				Jordan	1 patient		Transfusion dependent β-thal & HbS/b-thal	[63]
				Kuwait	25 patients		β -thal and sickle cell	[26]
				Iraq	Not available		β -thal intermedia	[47]
				Lebanon	2 patients		β -thal	[75]
				Algeria	4 patients		β -thal major, β -thal intermedia	[78]
				Qatar	23 alleles		Transfusion dependent β-thal	[70]
C.93–21 G > A	IVS-I-110  G > A	Splice site	Mediterranean	Saudi Arabia	103 patients		β -thal major, β -thal	[18,19,58,70]	Cyprus,Greece,Turkey	β+ -thal	[27–29]
				Oman	1 chromosome		β -thal	[20]
				The United Arab Emirates	8 chromosomes, 4 patients		β -thal	[22,79]
				Palestinian territories	142 alleles, 21 chromosomes		β -thal transfusion dependent & β -thal carrier, β -thal, β -thal intermedia, β -thal and sickle cell	[23,51,69,76]
				Syria	337 alleles, 52 patients		β -thal major, β -thal, β -thal carrier	[48,54,84]
				Morocco	15 chromosomes		β -thal	[30,67]
				Tunisia	100 chromosomes		β -thal major, β -thal carrier, HbS/b-thal, Hb C/b-thal, O-Arab/b-thal	[71]
				Libya	13 patients		β -thal	[81]
				Comoros	1 patient		β -thal	[31]
				Bahrain	1 patient		β -thal major & β -thal carrier	[24]
				Jordan	32 patients		Transfusion dependent β-thal & HbS/b-thal	[63]
				Kuwait	3 patients		β -thal and sickle cell	[26]
				Iraq	Not available		β -thal intermedia	[47]
				Lebanon	113 patients		β -thal	[75]
				Algeria	31 patients		β -thal major	[46]
				Egypt	33 patients		β -thal	[50]
				Qatar	4 alleles		Transfusion dependent β-thal	[70]
				Sudan	14 patients		β -thal	[32]
				Yemen	6 patients		β -thal	[33]
C.118 C > T	Codon 39 (C > T)	Nonsense	Mediterranean	Saudi Arabia	131 patients		β -thal major, HbA2 > 3%, β -thal	[18,19,55,58,77,83]	Argentina, Italy	β0 -thal	[34,82]
				Kuwait	30 patients		β -thal and sickle cell	[26,35]
				Oman	6 chromosomes		β -thal	[20,21]
				The United Arab Emirates	18 chromosomes, 11 patients		β -thal	[22,79]
				Palestinian territories	39 alleles, 3 chromosomes		β -thal transfusion dependent & β -thal carrier, β -thal, β -thal and sickle cell	[23,69,76]
				Syria	120 alleles, 44 patients		β -thal major, β -thal, β -thal carrier	[48,54,84]
				Morocco	91 chromosomes		β -thal	[30,67]
				Tunisia	232 chromosomes		β -thal major, β -thal carrier, HbS/b-thal, Hb C/b-thal, O-Arab/b-thal	[71]
				Comoros	1 patient		β -thal	[31]
				Bahrain	49 patients		β -thal major & β -thal carrier, β -thal and sickle cell	[24,25]
				Jordan	6 patients		Transfusion dependent β-thal & HbS/b-thal	[63]
				Iraq	Not available		β -thal intermedia	[47]
				Lebanon	1 patient		β -thal	[75]
				Algeria	52 patients		β -thal major	[46]
				Egypt	13 patients		β -thal	[50]
				Qatar	1 allele		Transfusion dependent β-thal	[70]
C.92 + 1 (G > A)	IVSI-1 (G > A)	Splice site	Mediterranean	Saudi Arabia	25 patients		β -thal major, HbA2 > 3%, β -thal	[19,55,58,77]	Czech Republic, Slovak, Spain	β0 -thal	[36,68]
				Oman	3 chromosomes		β -thal	[20,21]
				The United Arab Emirates	2 patients		β -thal	[79]
				Palestinian territories	83 alleles, 8 chromosomes		β -thal transfusion dependent & β -thal carrier, β -thal, β -thal intermedia, β -thal and sickle cell	[23,51,69,76]
				Syria	47 patients		β -thal major & β -thal carrier, β -thal intermedia	[48,85]
				Morocco	24 chromosomes		β -thal	[30,67]
				Tunisia	21 chromosomes		β -thal major, β -thal carrier HbS/b-thal, Hb C/b-thal, O-Arab/b-thal	[71]
				Libya	1 patient		β -thal	[81]
				Bahrain	26 patients		β -thal major & β -thal carrier, β -thal and sickle cell	[24,25]
				Jordan	13 patients		Transfusion dependent β-thal & HbS/b-thal	[63]
				Kuwait	25 patients		β -thal and sickle cell	[26]
				Iraq	Not available		β -thal intermedia	[47]
				Lebanon	49 patients		β -thal	[75]
				Algeria	12 patients		β -thal major	[46]
				Egypt	39 patients		β -thal	[50]
				Qatar	1 allele		Transfusion dependent β-thal	[70]
				Sudan	4 patients		β -thal	[32]
C.92 + 6 (T > C)	IVS I-6 (T > C)	Splice site	Mediterranean	Saudi Arabia	12 patients		β -thal major, HbA2 > 3%, β -thal	[55,58,77]	Malta, Portugal	β+ -thal	[37,38]
				Kuwait	11 patients		β -thal intermedia, β -thal and sickle cell	[26,35,80]
				The United Arab Emirates	12 chromosomes, 10 patients		β -thal	[22,79]
				Palestinian territories	116 alleles, 144 chromosomes		β -thal transfusion dependent & β -thal carrier, β -thal, β -thal intermedia, β -thal and sickle cell	[23,51,68,76]
				Syria	103 alleles		β -thal, β -thal major & β -thal carrier	[48,54]
				Morocco	5 chromosomes, 26 patients		β -thal	[30,67]
				Tunisia	3 chromosomes		β -thal major, β -thal carrier, HbS/b-thal, Hb C/b-thal, O-Arab/b-thal	[71]
				Libya	7 patients		β -thal	[81]
				Jordan	11 patients		Transfusion dependent β-thal & HbS/b-thal	[63]
				Iraq	Not available		β -thal intermedia	[47]
				Lebanon	47 patients		β -thal	[75]
				Egypt	27 patients		β -thal	[50]
				Sudan	7 patients		β -thal	[32]
C.315 + 1 G > A	IVSII-1 (G > A)	Splice site	Mediterranean, African American, Pakistani	Saudi Arabia	168 patients		β -thal major, HbA2 > 3%, β -thal	[18,19,55,58,77,83]	Iran	β0 -thal	[86]
				Kuwait	51 patients		β -thal, β -thal intermedia, β -thal and sickle cell	[26,35,39,80]
				Oman	7 patients		β -thal carrier	[40]
				The United Arab Emirates	23 chromosomes, 14 patients		β -thal	[22,79]
				Palestinian territories	8 alleles, 13 chromosomes		β -thal, β -thal intermedia, β -thal and sickle cell	[51,69,76]
				Syria	112 alleles, 30 patients		β -thal major, β -thal, β -thal carrier	[48,54,84]
				Tunisia	3 chromosomes		β -thal major, β -thal carrier, HbS/b-thal, Hb C/b-thal, O-Arab/b-thal	[71]
				Comoros	3 patients		β -thal	[31]
				Bahrain	6 patients		β -thal major & β -thal carrier	[24]
				Jordan	19 patients		Transfusion dependent β-thal & HbS/b-thal	[63]
				Iraq	Not available		β -thal intermedia	[47]
				Lebanon	28 patients		β -thal	[75]
				Algeria	2 patients		β -thal major, β -thal intermedia	[78]
				Egypt	2 patients		β -thal	[41]
				Qatar	6 alleles		Transfusion dependent β-thal	[70]
				Yemen	4 patients		β -thal	[33]
C.27dupG	Codon 8/9 (+G)	Frameshift	Asian Indian, Japanese, Pakistani	Saudi Arabia	33 patients		β -thal major, β -thal, β -thal	[18,19,55,58,83]	Pakistan, United Kingdom	β0 -thal	[42,43]
				Kuwait	26 patients		β -thal and sickle cell	[26,35]
				Oman	3 chromosomes		β -thal	[21]
				The United Arab Emirates	25 chromosomes, 16 patients		β -thal	[22,79]
				Palestinian territories	4 alleles, 4 chromosomes		β -thal, β -thal and sickle cell	[68,76]
				Syria	5 alleles, 1 patient		β -thal, β -thal major & β -thal carrier	[48,54]
				Bahrain	1 patient		β -thal major & β -thal carrier	[24]
				Iraq	Not available		β -thal intermedia	[47]
				Lebanon	1 patient		β -thal	[75]
				Egypt	Not available		β -thal major, β -thal intermedia	[49]
				Qatar	17 alleles		Transfusion dependent β-thal	[70]

Abbreviations: HGVS: Human Genome Variation Society; β -thal: Beta-thalassemia. * Numbers shown are the sum of patients, alleles or chromosomes with mutation reported in the used articles.

Figure 2. Distribution of HBB mutations in Arab countries. The green color indicates Arab countries. The mapping was limited to the most common and unique mutations only, the entire list of mutations are list in Supplementary Table 1: Beta-thalassemia HBB gene shared mutations between Arabs and other ethnic groups Note: The map is extracted from the free map product (http://english.freemap.jp/item/africa/africa_1.html)/Africa’s regional Thumbnail, under the Creative Commons Attribution 3.0 unported (CCBY3.0) license

Figure 3. Types of HBB gene mutations associated with β-thal in the Arab countries

Figure 4. Number of HBB mutations identified in each Arab country

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