Frameshift mutations with severe and moderate clinical phenotypes in Thai hemophilia A patients

First report of molecular diagnosis of Tunisian hemophiliacs A: Identification of 8 novel causative mutations

“…Insertions in the stretch of poly A nucleotides in exon 14 of the F8 gene are the cause of the moderate clinical severity in some cases [26,27]. Accordingly to these reported data, we can consider that also the new insertion of T in the stretches of poly T can be associated with moderate phenotype in our patient.…”

“…The novel insertion c.2236-2237insT and the previously reported insertion c.3870-3871insA identified in family 7 and 20 respectively (Table 2 ), are due to insertions of a ‘T’ nucleotide in the stretch of 3Ts at codon 727(746) and of an ‘A’ nucleotide in the stretch of 9As at codon1271(1290). Insertions in the stretch of poly A nucleotides in exon 14 of the F8 gene are the cause of the moderate clinical severity in some cases [ 26 , 27 ]. Accordingly to these reported data, we can consider that also the new insertion of T in the stretches of poly T can be associated with moderate phenotype in our patient.…”

First report of molecular diagnosis of Tunisian hemophiliacs A: Identification of 8 novel causative mutations

“…Insertions in the stretch of poly A nucleotides in exon 14 of the F8 gene are the cause of the moderate clinical severity in some cases [26,27]. Accordingly to these reported data, we can consider that also the new insertion of T in the stretches of poly T can be associated with moderate phenotype in our patient.…”

“…The novel insertion c.2236-2237insT and the previously reported insertion c.3870-3871insA identified in family 7 and 20 respectively (Table 2 ), are due to insertions of a ‘T’ nucleotide in the stretch of 3Ts at codon 727(746) and of an ‘A’ nucleotide in the stretch of 9As at codon1271(1290). Insertions in the stretch of poly A nucleotides in exon 14 of the F8 gene are the cause of the moderate clinical severity in some cases [ 26 , 27 ]. Accordingly to these reported data, we can consider that also the new insertion of T in the stretches of poly T can be associated with moderate phenotype in our patient.…”

Six years' experience performing RHD genotyping to confirm D− red blood cell units in Germany for preventing anti‐D immunizations

“…For instance, in RHD (147delA) a slippage in RHD Exon 1 at the AAAAGGGG sequence 16 nucleotides 5′ prime of the deletion at Position 147 could restore the reading frame, permitting the production of trace amounts of functional protein. Partial correction of similar frameshift mutations by compensatory ribosomal frameshift during expression has been reported for several genes, like apoB, 22 CA‐II, 23 and FVIII 24‐26 …”

Genotype and phenotype of haemophilia A in Thai patients

“…The FVIII protein would possibly be synthesized from the cells bearing normal FVIII allele. The deletion and insertion of ÔAÕ nucleotide in these two frameshift mutations occurred in the sequences within the runs of 9 As (at codons 1191-4) and 8 As (at codons 1439-41) in exon 14 of FVIII, respectively [28]. Thus, the present of FVIII:C activity might be because of postzygotic somatic mosaicism in this patient.…”

First report of molecular diagnosis of Tunisian hemophiliacs A: Identification of 8 novel causative mutations

“…Insertions in the stretch of poly A nucleotides in exon 14 of the F8 gene are the cause of the moderate clinical severity in some cases [26,27]. Accordingly to these reported data, we can consider that also the new insertion of T in the stretches of poly T can be associated with moderate phenotype in our patient.…”

“…The novel insertion c.2236-2237insT and the previously reported insertion c.3870-3871insA identified in family 7 and 20 respectively (Table 2 ), are due to insertions of a ‘T’ nucleotide in the stretch of 3Ts at codon 727(746) and of an ‘A’ nucleotide in the stretch of 9As at codon1271(1290). Insertions in the stretch of poly A nucleotides in exon 14 of the F8 gene are the cause of the moderate clinical severity in some cases [ 26 , 27 ]. Accordingly to these reported data, we can consider that also the new insertion of T in the stretches of poly T can be associated with moderate phenotype in our patient.…”

Six years' experience performing RHD genotyping to confirm D− red blood cell units in Germany for preventing anti‐D immunizations

“…For instance, in RHD (147delA) a slippage in RHD Exon 1 at the AAAAGGGG sequence 16 nucleotides 5′ prime of the deletion at Position 147 could restore the reading frame, permitting the production of trace amounts of functional protein. Partial correction of similar frameshift mutations by compensatory ribosomal frameshift during expression has been reported for several genes, like apoB, 22 CA‐II, 23 and FVIII 24‐26 …”

Genotype and phenotype of haemophilia A in Thai patients

“…The FVIII protein would possibly be synthesized from the cells bearing normal FVIII allele. The deletion and insertion of ÔAÕ nucleotide in these two frameshift mutations occurred in the sequences within the runs of 9 As (at codons 1191-4) and 8 As (at codons 1439-41) in exon 14 of FVIII, respectively [28]. Thus, the present of FVIII:C activity might be because of postzygotic somatic mosaicism in this patient.…”

First report of molecular diagnosis of Tunisian hemophiliacs A: Identification of 8 novel causative mutations

“…Insertions in the stretch of poly A nucleotides in exon 14 of the F8 gene are the cause of the moderate clinical severity in some cases [26,27]. Accordingly to these reported data, we can consider that also the new insertion of T in the stretches of poly T can be associated with moderate phenotype in our patient.…”

“…The novel insertion c.2236-2237insT and the previously reported insertion c.3870-3871insA identified in family 7 and 20 respectively (Table 2 ), are due to insertions of a ‘T’ nucleotide in the stretch of 3Ts at codon 727(746) and of an ‘A’ nucleotide in the stretch of 9As at codon1271(1290). Insertions in the stretch of poly A nucleotides in exon 14 of the F8 gene are the cause of the moderate clinical severity in some cases [ 26 , 27 ]. Accordingly to these reported data, we can consider that also the new insertion of T in the stretches of poly T can be associated with moderate phenotype in our patient.…”

Six years' experience performing RHD genotyping to confirm D− red blood cell units in Germany for preventing anti‐D immunizations

“…For instance, in RHD (147delA) a slippage in RHD Exon 1 at the AAAAGGGG sequence 16 nucleotides 5′ prime of the deletion at Position 147 could restore the reading frame, permitting the production of trace amounts of functional protein. Partial correction of similar frameshift mutations by compensatory ribosomal frameshift during expression has been reported for several genes, like apoB, 22 CA‐II, 23 and FVIII 24‐26 …”

Genotype and phenotype of haemophilia A in Thai patients

“…The FVIII protein would possibly be synthesized from the cells bearing normal FVIII allele. The deletion and insertion of ÔAÕ nucleotide in these two frameshift mutations occurred in the sequences within the runs of 9 As (at codons 1191-4) and 8 As (at codons 1439-41) in exon 14 of FVIII, respectively [28]. Thus, the present of FVIII:C activity might be because of postzygotic somatic mosaicism in this patient.…”