Table 2.

NIPD approaches implemented for determining fetal genotype in beta-thalassemia

Author, year (Ref)	Mutations	Methods	Sens.	Spec.
Li et al. , 2005 (49)	IVSI-1, IVSI-6, IVSI-110, and codon 39 (compound heterozygote)	Peptide-nucleic-acid clamp and allele-specific real-time PCR	100	93.8
Galbiati et al. , 2016 (39)	Cd39 and IVSI.110	COLD-PCR and microarray	100	100
Mortazavipour et al. , 2020 (48)	IVSII-1	COLD-PCR	NA
Phylipsen et al. , 2012 (50)	12 different fragments along with the β-globin gene cluster	PAP and MCA	NI
Papasavva et al. , 2008 (51)	11 SNPs	APEX method	NI
Yi et al. , 2010 (52)	IVSII-654 (C $\to$ T)	PCR/LDR/capillary electrophoresis	NI
Yi et al. , 2010 (53)	CD17 (A $\to$ T)	PCR/LDR/capillary electrophoresis	1:5000	NI
Chiu et al. , 2002 (54)	41/42 (–CTTT)	Real-time PCR	100	100
Lun et al. , 2008 (44)	CD41/42 (–CTTT )	RMD & NASS	NI
Li et al. , 2009 (55)	Cd39	Mutation-specific PCR & MALDI TOF	NA
Ramezanzadeh et al. , 2016 (56)	CD44, IVSI-1, FR8-9, and IVSI-5	Allele-specific real-time PCR	100	100
Wang et al. , 2017 (45)	CD41-42 (-TTCT)	RHD	100	100
Camunas-Soler et al. , 2018 (22)	Droplet digital PCR (RMD)	99.8	99.8
Chan et al. , 2010 (57)	4 SNPs in connection with HBB gene	AS-APEX	100	100
Byrou et al. , 2018 (38)	2 SNPs (rs7480526 and rs968857)	Fast TG COLD- PCR	NA
Yenilmez et al. , 2013 (46)	Used 4 primers: P1:Cap +22 (G $>$ A) and-30 (C $>$ T) P2: IVSI-1 (G $>$ A), IVSI-5 (G $>$ A), IVSI-6 (T $>$ C), IVSI-110, (G $>$ A), Cd8 ( $-$ AA), Cd9/10 (+T), Cd15 (G $>$ A), and Cd39 (C $>$ T) P3: IVSII-1 (G $>$ A) P4: IVSII-745 (C $>$ G) and IVSII-848 (C $>$ A)	HRM	100	100
Saba et al. , 2017 (47)	c.118C4T	Semiconductor sequencing	100	100
Lam et al. , 2012 (29)	Cd41/42, 28(A $>$ G), and CD17	MPS	100	100
NIPD: Non-invasive prenatal diagnosis, Spec: Specificity (%), Sens: Sensitivity (%), NA: Not applicable, NI: Not indicated, PAP: Pyrophosphorolysis-activated polymerization, MCA: Melting curve analysis, SNPs: Single nucleotide polymorphisms, LDR: Ligase detection reaction, NASS: Nucleic acid size selection, MALDI TOF: Matrix assisted laser desorption ionization time of flight, RMD: Relative mutation dosage, RHD: Relative haplotype dosage, AS: Allele specific, APEX: Arrayed primer extension, TG COLD-PCR: Temperature gradient coamplification at lower denaturation temperature PCR, HRM: High resolution melting, MPS: Massively parallel sequencing, PCR: Polymerase chain reaction