Expanded carrier screening and preimplantation genetic diagnosis in a couple who delivered a baby affected with congenital factor VII deficiency.

BACKGROUND: Preimplantation genetic diagnosis (PGD) is a powerful tool for preventing the transmission of Mendelian disorders from generation to generation. However, PGD only can identify monogenically inherited diseases, but not other potential monogenic pathologies. We aimed to use PGD to deliver a healthy baby without congenital FVII deficiency or other common Mendelian diseases in a couple in which both individuals carried a deleterious mutation in the F7 gene. METHODS: After both members of the couple were confirmed to be carriers of the F7 gene mutation by Sanger sequencing, expanded carrier screening (ECS) for 623 recessive inheritance diseases was performed to detect pathological mutations in other genes. PGD and preimplantational genetic screening (PGS) were employed to exclude monogenic disorders and aneuploidy for their embryos. RESULTS: ECS using targeted capture sequencing technology revealed that the couple carried the heterozygous disease-causative mutations c.3659C > T (p.Thr1220Ile) and c.3209G > A (p.Arg1070Gln) in the CFTR gene. After PGD and PGS, one of their embryos that was free of congenital FVII deficiency, cystic fibrosis (CF) and aneuploidy was transferred, resulting in the birth of a healthy 3200 g male infant. CONCLUSION: We successfully implemented PGD for congenital FVII deficiency and PGD after ECS to exclude CF for the first time to the best of our knowledge. Our work significantly improved the reproductive outcome for the couple and provides a clear example of the use of ECS combined with PGD to avoid the delivery of offspring affected not only by identified monogenically inherited diseases but also by other potential monogenic pathologies and aneuploidy.

Bleeding prophylaxis in a child with cleft palate and factor VII deficiency: a case report.

The association between factor VII deficiency and cleft palate has never been described. The case of a child with cleft palate and factor VII deficiency who successfully underwent palatoplasty is described in this article. To allow surgical treatment, through maintenance of a normal prothrombin time, the patient was given 15 microg/kg of recombinant factor VIIa every 12 hours, starting 20 minutes before surgery and ending the third postoperative day. No abnormal perioperative bleeding was observed. Use of recombinant factor VIIa in bleeding prophylaxis or treatment is widespread. Doses are much higher in these cases. The reduction of dosage allows easier administration, especially in pediatric patients, without affecting drug efficacy.