Preimplantation genetic testing for monogenic disorders (PGT-M) offers an alternative strategy to prevent children from being born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes: a retrospective study.

Abstract

Preimplantation genetic testing for monogenic disorders (PGT-M) is now widely used as an effective strategy to prevent various monogenic or chromosomal diseases. In this retrospective study, couples with a family history of hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes and/or carrying the pathogenic genes underwent PGT-M to prevent children from inheriting disease-causing gene mutations from their parents and developing known genetic diseases. After PGT-M, unaffected (i.e., normal) embryos after genetic detection were transferred into the uterus of their corresponding mothers. A total of 43 carrier couples with the following hereditary neurological diseasesor metabolic diseases dominated by nervous system phenotypesunderwent PGT-M: Duchenne muscular dystrophy (13 families); methylmalonic acidemia (7 families); spinal muscular atrophy (5 families); infantile neuroaxonal dystrophyand intellectual developmental disorder(3 families each); Cockayne syndrome(2 families); Menkes disease, spinocerebellar ataxia, glycine encephalopathy with epilepsy,Charcot-Marie-Tooth disease, mucopolysaccharidosis, Aicardi-Goutieres syndrome, adrenoleukodystrophy, phenylketonuria, amyotrophic lateral sclerosis, and Dravet syndrome (1 family each). After 53 PGT-M cycles,the final transferable embryo rate was 12.45%, the clinical pregnancy rate was 74.19%, and the live birth rate was 89.47%;a total of 18 unaffected (i.e., healthy) children were born to these families. This study highlights the importance of PGT-M in preventing children born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes.