Pregnancy outcome after preimplantation genetic diagnosis in an affected couple with X-linked adrenoleukodystrophy

Iglesias, Miriam Hernández; Ceballos, Patricia I.; Giménez, Carles; García-Nebreda, Maria Isabel; Domı́nguez, Raquel; García-Enguidanos, A.

doi:10.1016/j.fertnstert.2008.02.011

Cited by 4 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 60 In a different sex selection approach, male embryos derived from a father diagnosed with X-ALD and a healthy mother were selected since these are all unaffected. 61 …”

Section: Diagnosis Of X-aldmentioning

confidence: 99%

The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis

Wiesinger

Eichler

Berger

2015

TACG

View full text Add to dashboard Cite

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene encoding a peroxisomal ABC transporter. In this review, we compare estimates of incidence derived from different populations in order to provide an overview of the worldwide incidence of X-ALD. X-ALD presents with heterogeneous phenotypes ranging from adrenomyeloneuropathy (AMN) to inflammatory demyelinating cerebral ALD (CALD). A large number of different mutations has been described, providing a unique opportunity for analysis of functional domains within ABC transporters. Yet the molecular basis for the heterogeneity of clinical symptoms is still largely unresolved, as no correlation between genotype and phenotype exists in X-ALD. Beyond ABCD1, environmental triggers and other genetic factors have been suggested as modifiers of the disease course. Here, we summarize the findings of numerous reports that aimed at identifying modifier genes in X-ALD and discuss potential problems and future approaches to address this issue. Different options for prenatal diagnosis are summarized, and potential pitfalls when applying next-generation sequencing approaches are discussed. Recently, the measurement of very long-chain fatty acids in lysophosphatidylcholine for the identification of peroxisomal disorders was included in newborn screening programs.

show abstract

“… 60 In a different sex selection approach, male embryos derived from a father diagnosed with X-ALD and a healthy mother were selected since these are all unaffected. 61 …”

Section: Diagnosis Of X-aldmentioning

confidence: 99%

The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis

Wiesinger

Eichler

Berger

2015

TACG

View full text Add to dashboard Cite

show abstract

“…Only one prior study reported by Miriam Iglesias et al in 2008 that made use of PGD to prevent ALD indicated a successful pregnancy. [29][30][31][32] Up to date, molecular biology becoming more and more essential with many advances has led to the fact that, once the mutation is identified, the couples would undergo specific genetic diagnosis instead of simple sex selection. Hence, our study with the successful live birth after a full-term pregnancy is more suitable with the modern trend and avoids ethical concerns by not choosing the sex but applying sequencing technology to determine the pathogenic gene.…”

Section: Discussionmentioning

confidence: 99%

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

Tien

Van

Ngoc

et al. 2021

TACG

View full text Add to dashboard Cite

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.

show abstract

The Changing Face of Adrenoleukodystrophy

et al. 2020

View full text Add to dashboard Cite

Adrenoleukodystrophy (ALD) is a rare X-linked disorder of peroxisomal oxidation due to mutations in ABCD1. It is a progressive condition with a variable clinical spectrum that includes primary adrenal insufficiency, myelopathy, and cerebral ALD. Adrenal insufficiency affects over 80% of ALD patients. Cerebral ALD affects one-third of boys under the age of 12 and progresses to total disability and death without treatment. Hematopoietic stem cell transplantation (HSCT) remains the only disease-modifying therapy if completed in the early stages of cerebral ALD, but it does not affect the course of adrenal insufficiency. It has significant associated morbidity and mortality. A recent gene therapy clinical trial for ALD reported short-term MRI and neurological outcomes comparable to historical patients treated with HSCT without the associated adverse side effects. In addition, over a dozen states have started newborn screening (NBS) for ALD, with the number of states expecting to double in 2020. Genetic testing of NBS-positive neonates has identified novel variants of unknown significance, providing further opportunity for genetic characterization but also uncertainty in the monitoring and therapy of subclinical and/or mild adrenal insufficiency or cerebral involvement. As more individuals with ALD are identified at birth, it remains uncertain if availability of matched donors, transplant (and, potentially, gene therapy) centers, and specialists may affect the timely treatment of these individuals. As these promising gene therapy trials and NBS transform the clinical management and outcomes of ALD, there will be an increasing need for the endocrine management of presymptomatic and subclinical adrenal insufficiency. (Endocrine Reviews 41: 1 – 17, 2020)

show abstract

Pregnancy outcome after preimplantation genetic diagnosis in an affected couple with X-linked adrenoleukodystrophy

Cited by 4 publications

References 12 publications

The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis

The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis

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

The Changing Face of Adrenoleukodystrophy

Contact Info

Product

Resources

About