PMC7973284_01
(A) Pedigree of the family. The white square represents healthy male individuals; the black square indicates affected male individuals; the black circle with a dot in the middle indicates carrier female individuals. (B) The inspection report of III-1. (C) Mutation screening of the principle of family members using Sanger sequencing. The red arrow indicates the mutation site of (Phe690Leu)/c.2070C > A of F8 at an individual person.
fgene-11-589899-g001.jpg
PMC7973284_01_fgene-11-589899-g001.jpg
F1
A woman (II-2) presented with no apparent clinical phenotype of hemophilia A came to our assisted reproduction center for PGT-M counseling because her son (III-1) and her brother (II-1) were both affected by hemophilia A (Figure 1A). The hemophilia A patients suffered from recurrent hemarthrosis and continuous bleeding after an injury (Figure 1B and Supplementary Figure S1). The result is shown in Figure 1C; a variation, c.2070C > A in exon 13 of F8, was found in the mother (II-2).
PMC7973284_02
(A) The copy number variation (CNV) detection and (B) the mutation screening of the seven blastocysts.
fgene-11-589899-g002.jpg
PMC7973284_03_fgene-11-589899-g002.jpg
F2
A of the mother-II-2. According to the doctor's opinion, FVIII activity became almost normal (Figure 3D and Supplementary Figure S2).
(A) The copy number variation (CNV), (B) mutation, and (C) single nucleotide polymorphism (SNP) detection of amniotic fluid at the 18th pregnancy week after transfer blastocyst 4479405. (D) The inspection report of newborn 4479405. (E) The consensus of 690 Phe of F8 among different specials. (F) The 3D structure of wild-type FVIII and mutant FVIII. The red arrow represents the conservation of the site Phe690 of F8 among different species.
fgene-11-589899-g003.jpg
PMC7973284_03_fgene-11-589899-g003.jpg
F3
A of the mother-II-2. According to the doctor's opinion, FVIII activity became almost normal (Figure 3D and Supplementary Figure S2). The protein conservation of Phe690 of F8 showed high consensus among Homo sapiens, Pan troglodytes, Canis lupus familiaris, Mus musculus, and Sus scrofa; high consensus was labeled as red color (Figure 3E, arrow). The possible damaging effect of the mutation to FVIII protein 3D structure and software-predicted damaging parameters are illustrated in Figure 3F and listed in Supplementary Figure S3.
PMC7973284_03
(A) The copy number variation (CNV) detection and (B) the mutation screening of the seven blastocysts.
fgene-11-589899-g002.jpg
PMC7973284_03_fgene-11-589899-g002.jpg
F2
A of the mother-II-2. According to the doctor's opinion, FVIII activity became almost normal (Figure 3D and Supplementary Figure S2).
(A) The copy number variation (CNV), (B) mutation, and (C) single nucleotide polymorphism (SNP) detection of amniotic fluid at the 18th pregnancy week after transfer blastocyst 4479405. (D) The inspection report of newborn 4479405. (E) The consensus of 690 Phe of F8 among different specials. (F) The 3D structure of wild-type FVIII and mutant FVIII. The red arrow represents the conservation of the site Phe690 of F8 among different species.
fgene-11-589899-g003.jpg
PMC7973284_03_fgene-11-589899-g003.jpg
F3
A of the mother-II-2. According to the doctor's opinion, FVIII activity became almost normal (Figure 3D and Supplementary Figure S2). The protein conservation of Phe690 of F8 showed high consensus among Homo sapiens, Pan troglodytes, Canis lupus familiaris, Mus musculus, and Sus scrofa; high consensus was labeled as red color (Figure 3E, arrow). The possible damaging effect of the mutation to FVIII protein 3D structure and software-predicted damaging parameters are illustrated in Figure 3F and listed in Supplementary Figure S3.