Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemoglobinopathies, as a group, are one of the most common serious monogenic diseases in the world. An accepted and widely adopted approach to reduce the number of new cases involves carrier-screening programs, with the option of prenatal diagnosis (PND) or preimplantation diagnosis (preimplantation genetic testing for monogenic disease, PGT-M) for carrier couples. The aim of PND is to provide an accurate result as early in pregnancy as possible, which necessitates prior identification of the parental disease-causing mutations, as well as safe and timely biopsy of fetal material. PGT-M aims to characterize the genetic status of in vitro fertilized embryos during assisted reproductive technology (ART), in a few cells biopsied from oocytes/zygotes or embryos, in order to initiate an unaffected pregnancy. Another application of PGT-M is preimplantation genetic diagnosis for human leukocyte antigen (PGD-HLA), which, in addition to identifying unaffected embryos, also characterizes the embryos that are HLA compatible with an existing affected child requiring a hemopoietic stem cell transplantation (HSCT). This review outlines the current practices related to these procedures, with emphasis on the aspects related to laboratory techniques. Finally, future prospects related to developments in noninvasive prenatal diagnosis are discussed.
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PMID:Prenatal and preimplantation diagnosis of hemoglobinopathies. 2974 Dec 47

Preimplantation genetic testing-human leukocyte antigen '(PGT-HLA) only' refers to the HLA typing of single or few cells biopsied from in vitro fertilized preimplantation embryos. The aim of the procedure is to establish a pregnancy, in which the fetus is HLA compatible with an affected sibling in need of a hematopoietic stem cell transplantation (HSCT). During PGT-M-HLA, the identification of a HLA-compatible embryo is combined with the detection of mutation(s) underlying immunodeficiencies and hemoglobinopathies. We report a combined retrospective and prospective cohort analysis of PGT-(M-)HLA procedures carried out from 1998 until 2017, with follow-up of transplantations to 2019. During the study period, 234 couples from 22 countries were invited for a multidisciplinary consultation. Two couples were rejected and 70 couples declined (various reasons), leaving 162 couples for which 414 clinical cycles were carried out. Cleavage stage biopsy followed by single-cell multiplex PCR for short tandem repeat-based haplotyping was applied in most cases (98.7%). The diagnostic efficiency was high (94.8%) but only 16.5% of the embryos was genetically suitable for transfer. Fresh and frozen-thawed embryo transfer resulted in 67 clinical pregnancies, 63 deliveries, and 74 live births, of which 60 children were HLA compatible. This yielded a live birth delivery rate of 30.3% per transfer. Information on neonatal characteristics of the matching PGT-(M-)HLA children showed reassuring outcomes. So far, HSCT was carried out successfully for 25 out of 26 cases. In conclusion, our data show that PGT-(M-)HLA is a valuable procedure: the high complexity and limited delivery rate are balanced by the successful HSCT outcome and the positive impact on families.
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PMID:Preimplantation genetic testing with HLA matching: from counseling to birth and beyond. 3210 23