- Invited speaker presentation
- Open Access
Preimplantation genetic diagnosis for TTR-FAP in Portugal
© Carvalho 2015
- Published: 2 November 2015
- Embryo Transfer
- Preimplantation Genetic Diagnosis
- Term Pregnancy
- Systemic Amyloidosis
Portuguese Familial Amyloidotic Polyneurophaty (FAP) (OMIM #105210) is a rare systemic amyloidosis characterized by a progressive, autonomic and sensory-motor neuropathy. FAP is an autosomal dominant disorder caused by mutations in the transthyretin (TTR) gene. Preimplantation genetic diagnosis (PGD) is currently one of the options available for couples at-risk to avoid disease transmission. The review the PGD cycles for TTR-FAP performed in the last 15 years in Portugal will be presented.
Embryos were biopsed at day 3 of development and diagnosis was initially performed using fluorescent PCR primers designed to amplify the p.Val50Met in exon 2 of the TTR gene and is currently done by multiplex PCR for the mutation detection and polymorphic markers.
Two hundred and thirty-five clinical cycles were performed in 118 couples (74 with paternal and 44 with maternal mutation), with a mean number of 2 cycles per couple and a mean maternal age of 31.4 years old. The mean number of MII injected oocytes per cycle was 8.7. Fertilization and cleavage rates were 74.5% and 98.2%, respectively. Eighty-nine percent of embryos were biopsied (mean number = 5.8) and amplification was obtained in 94% with a ratio of normal versus mutated embryos of 1:1,3 (p < 0.0001). Interestingly, if only the cycles of paternal transmission were considered the ratio of normal versus mutated embryos was 1:1,03 (p=0,7018) whereas if the cycles of maternal transmission were analyzed the ratio of normal versus mutated embryos was 1:1,77 (p<0,0001). One hundred and fifty-eight cycles had embryo transfer (mean embryo number = 1.7) leading to 57 biochemical (36%) and 50 clinical pregnancies (32%) (45 term pregnancies, 3 ongoing pregnancies and 2 miscarriages). Three pregnancies correspond to frozen embryos transfers. Thirty-seven term pregnancies were singleton (mean gestational age = 38.4W; average weight at birth = 3093g), 7 were twins (mean gestational age = 34.5W; average weight at birth = 2310g) and one was a triplet pregnancy (two embryos transfer) (gestational age = 34W; average weight at birth = 1700g).
PGD for Portuguese type TTR-FAP is a well established procedure allowing the birth of unaffected children with a take-home baby rate similar to the one described in the literature.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.