Successful Pregnancy Following Preimplantation Genetic Diagnosis of Adrenoleukodystrophy by Detection of Mutation on the ABCD1 Gene

Abstract

Background

Adrenoleukodystrophy (ALD) is a rare sex-linked recessive disorder that disrupts adrenal gland function and the white matter of the nervous system. According to recent epidemiological statistics, up to this moment, the disease is the most recorded peroxisomal disorder. ABCD1 is a gene related to ALD, with more than 850 unique mutations have been reported. Early diagnosis of the disease would help to consult families with ALD to plan for interventions to prevent passing along the pathogenic mutations to their children.

Material and Methods

A heterozygous ABCD1 gene mutation related to ALD found in a Vietnamese woman was used to design primers for the polymerase chain reaction (PCR) to amplify the segment spanning the mutation. Then, combining sequencing methods for the PCR products, especially Sanger sequencing and next-generation sequencing (NGS), a protocol was developed to detect mutations on the ABCD1 gene to apply for the DNA samples of in-vitro fertilization (IVF) embryos biopsied at the blastocyst stage to screen for pathogenic alleles.

Results

The established protocol for PGD of ALD detected mutant alleles in 5/8 embryos (62.5%), while the remaining 3 embryos (37.5%) did not carry any mutation. One of the 3 embryos was transferred, and a healthy female baby was born after a full-term pregnancy.

Conclusion

The developed protocol was helpful for the preimplantation genetic diagnosis process to help families with the monogenic disease of ALD but wish to have healthy children.

Keywords:

• adrenoleukodystrophy
• ALD
• peroxisome disorder
• ABCD1 gene mutation
• preimplantation genetic diagnosis
• PGD

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author, upon reasonable request. If you have concerns about sharing the data, please contact [email protected].

Ethical Statements

All people described in this research were signed written informed consent for the publication of the case details, and the protocol was approved by the Ethical Review Committee of Vietnam Military Medical University (No.1068/2019/VMMU-IRB). This study was conducted following the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Acknowledgments

We thank all the staff in the Department of Biology and Genetics, Military institute of clinical Embryology and Histology, and the Director board of Military Hospital 103 for supporting this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declared no potential conflicts of interest for this work nor the research, authorship, and publication of this article.

Additional information

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.