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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

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Background

Preimplantation genetic testing for monogenic disorders (PGT-M) is now widely used as an effective strategy to prevent various monogenic or chromosomal diseases.

Material and methods

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.

Results

A total of 43 carrier couples with the following hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes underwent PGT-M: Duchenne muscular dystrophy (13 families); methylmalonic acidemia (7 families); spinal muscular atrophy (5 families); infantile neuroaxonal dystrophy and 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.

Conclusions

This study highlights the importance of PGT-M in preventing children born with hereditary neurological diseases or metabolic diseases dominated by nervous system phenotypes.

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Data availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

PGT:

Preimplantation genetic testing

PGT-M:

PGT for monogenic disorders

PGT-A:

PGT for aneuploidy

ICSI:

Intracytoplasmic sperm injection

HND:

Hereditary neurological diseases

NGS:

Next‑generation sequencing

SNP:

Single nucleotide polymorphisms

PCR:

Polymerase chain reaction

HCG:

Human chorionic gonadotropin

WGA:

Whole genome amplification

XR:

X-chromosome recessive

XD:

X-chromosome dominant

AD:

Autosomal dominant

AR:

Autosomal recessive

BMI:

Body mass index

E2:

Estradiol

LH:

Luteinizing hormone

FSH:

Follicle-stimulating hormone

PRL:

Prolactin

T:

Testosterone

PR:

Progressive motility

DFI:

DNA fragmentation index

HDS:

High DNA stainability

Gn:

Gonadotropins

DMD:

Duchenne muscular dystrophy

SMA:

Spinal muscular atrophy

CMT:

Charcot-Marie-Tooth

ALS:

Amyotrophic lateral sclerosis

SCA:

Spinocerebellar ataxias

GCE1:

Glycine encephalopathy 1

ALD:

Adrenoleukodystrophy

MPS:

Mucopolysaccharidosis

INAD:

Infantile neuroaxonal dystrophy

PKU:

Phenylketonuria

MMA:

Methylmalonic acidemia

MNK:

Menkes disease

DRVT:

Dravet syndrome

CSA:

Cockayne syndrome, type A

AGS:

Aicardi–Goutieres syndrome

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Acknowledgements

The authors thank all the reproductive physicians, embryologists, and related staff involved in this study. The authors also thank all the patients who participated in this study.

Funding

This research was funded by the National Natural Science Foundation of China, grant number 82001635; the National Key R&D Program of China, grant number 2021YFC2700901; the Clinical Medical Research Transformation Project of Anhui Province, grant number 202204295107020012; the Foundation for Selected Scientists Studying Abroad of Anhui Province, grant number 2022LCX015; the Program for Outstanding Young Talents in University of Anhui, grant number gxyqZD2022027; and the Major Science and Technology Project of Anhui province, grant number 202003a07020012.

Author information

Author notes

  1. Weiwei Zou, Min Li, Xiaolei Wang, and Hedong Lu contributed equally to this work.

Authors and Affiliations

  1. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China

    Weiwei Zou, Min Li, Xiaolei Wang, Hedong Lu, Yan Hao, Dawei Chen, Shasha Zhu, Dongmei Ji, Zhiguo Zhang, Ping Zhou & Yunxia Cao

  2. NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei, 230032, Anhui, China

    Weiwei Zou, Min Li, Xiaolei Wang, Hedong Lu, Ping Zhou & Yunxia Cao

  3. Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China

    Weiwei Zou, Min Li, Xiaolei Wang, Hedong Lu, Yan Hao, Dawei Chen, Shasha Zhu, Ping Zhou & Yunxia Cao

  4. Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No 81 Meishan Road, Hefei, 230032, Anhui, China

    Yan Hao, Dawei Chen, Shasha Zhu, Dongmei Ji & Zhiguo Zhang

  5. Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases, No 81 Meishan Road, Hefei, 230032, Anhui, China

    Dongmei Ji & Zhiguo Zhang

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  1. Weiwei Zou
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  2. Min Li
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Contributions

WZ and ML were responsible for statistical analysis and writing the first draft; XW and HL were responsible for data collection and charting; WZ was mainly responsible for supervising the research, conception, and review of papers; WZ, PZ, and YC were responsible for the major revisions of the review; and YH, DC, SZ, DJ, and ZZ participated in the revision of this review. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Weiwei Zou, Ping Zhou or Yunxia Cao.

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Ethics approval

This study was approved by the Ethics Committee of Anhui Medical University (No.2017002). Since this study is retrospective, the ethics committee of Anhui Medical University waived written informed consent. All methods were carried out in strict accordance with the relevant guidelines and regulations.

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Informed consent was obtained from all the parents.

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Zou, W., Li, M., Wang, X. et al. 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. J Assist Reprod Genet 41, 1245–1259 (2024). https://doi.org/10.1007/s10815-024-03057-1

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