First preimplantation genetic testing case for monogenic disease in Latvia

Perminov, Dmitry; Voložonoka, Ludmila; Kornejeva, Liene; Jokste-Pțmane, Evija; Blumberga, Arita; Krasucka, Sandra; Seimuškina, Nellija; Kovaļova, Irina; Fodina, Violeta

doi:10.1080/09513590.2017.1404239

Cited by 3 publications

(2 citation statements)

References 3 publications

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“…PGT-M with STR haplotyping was performed according to previously validated protocols [9] , [18] . The patient gave birth to a healthy boy who did not demonstrate any clinical symptoms linked to XLHED.…”

Section: Discussionmentioning

confidence: 99%

“…An in vitro fertilisation cycle was performed according to standard controlled ovarian hyperstimulation protocols. Preimplantation genetic testing for aneuploidies (PGT-A) and monogenic diseases (PGT-M) was carried out as described elsewhere [9] , [18] . Selection of EDA -linked short tandem repeats (STR) flanking the EDA gene 2.5 Mb upstream and downstream was performed using the UCSC Genome Browser.…”

Section: Methodsmentioning

confidence: 99%

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A novel EDA variant causing X-linked hypohidrotic ectodermal dysplasia: Case report

Alksere

Kornejeva

Grinfelde

et al. 2021

Molecular Genetics and Metabolism Reports

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Hereditary ectodermal dysplasias are a complex group of inherited disorders characterised by abnormalities in two or more ectodermal derivatives (skin, nails, sweat glands, etc. ). There are two main types of these disorders – hidrotic and hypohidrotic/anhidrotic ectodermal dysplasias. Hypohidrotic ectodermal dysplasia (HED) or Christ-Siemens-Touraine syndrome (OMIM: 305100 ) occurs in 1 out of 5000–10,000 births [19] and has an X-linked recessive inheritance pattern (X-linked hypohydrotic ectodermal dysplasia – XLHED) [2] . The main cause of XLHED is a broad range of pathogenic variants in the EDA gene (HGNC:3157, Xq12-13) which encodes the transmembrane protein ectodysplasin-A [4] . We report here the case of a patient with a novel inherited allelic variant in the EDA gene – NM_001399.5:c.337C>T (p.Gln113*) – in the heterozygous state. Targeted family member screening was conducted and other carriers of this EDA gene pathogenic variant were identified and phenotypically characterised. The patient subsequently underwent in vitro fertilisation with preimplantation genetic testing for monogenic diseases (PGT-M).

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A novel EDA variant causing X-linked hypohidrotic ectodermal dysplasia: Case report

Alksere

Kornejeva

Grinfelde

et al. 2021

Molecular Genetics and Metabolism Reports

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On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability

Khristich

Mirkin

2020

Journal of Biological Chemistry

216

261

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Expansions of simple tandem repeats are responsible for almost 50 human diseases, the majority of which are severe, degenerative, and not currently treatable or preventable. In this review, we first describe the molecular mechanisms of repeat-induced toxicity, which is the connecting link between repeat expansions and pathology. We then survey alternative DNA structures that are formed by expandable repeats and review the evidence that formation of these structures is at the core of repeat instability. Next, we describe the consequences of the presence of long structure-forming repeats at the molecular level: somatic and intergenerational instability, fragility, and repeat-induced mutagenesis. We discuss the reasons for gender bias in intergenerational repeat instability and the tissue specificity of somatic repeat instability. We also review the known pathways in which DNA replication, transcription, DNA repair, and chromatin state interact and thereby promote repeat instability. We then discuss possible reasons for the persistence of disease-causing DNA repeats in the genome. We describe evidence suggesting that these repeats are a payoff for the advantages of having abundant simple-sequence repeats for eukaryotic genome function and evolvability. Finally, we discuss two unresolved fundamental questions: (i) why does repeat behavior differ between model systems and human pedigrees, and (ii) can we use current knowledge on repeat instability mechanisms to cure repeat expansion diseases?

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Preimplantation Genetic Diagnosis of Neurodegenerative Diseases: Review of Methodologies and Report of Our Experience as a Regional Reference Laboratory

Liao

Chang

et al. 2019

Diagnostics

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Preimplantation genetic diagnosis (PGD) has become a crucial approach in helping carriers of inherited disorders to give birth to healthy offspring. In this study, we review PGD methodologies and explore the use of amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) and/or linkage analysis for PGD in neurodegenerative diseases that are clinically relevant with typical features, such as late onset, and which are severely debilitating. A total of 13 oocyte retrieval cycles were conducted in 10 cases with various neurodegenerative diseases. Among the 59 embryos analyzed, 49.2% (29/59) were unaffected and 50.8% (30/59) were affected. Of the 12 embryo transfer cycles, three resulted in pregnancy, and all pregnancies were delivered. The implantation rate and livebirth rate were 23.1% (3/13) per oocyte retrieval cycle and 25.0% (3/12) per embryo transfer cycle. Allele dropout (ADO) was noted in two embryos that were classified as unaffected by ARMS-qPCR but were evidenced as affected after prenatal diagnosis, rendering the false negative rate as 6.3% (2/32). Four among the 13 cycles underwent PGD by ARMS-qPCR coupled with linkage analysis, and all were correctly diagnosed. We conclude that PGD by ARMS-qPCR and/or linkage analysis is a feasible strategy, whereas ADO is a concern when ARMS-qPCR is used as the sole technology in PGD, especially in autosomal dominant diseases.

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First preimplantation genetic testing case for monogenic disease in Latvia

Cited by 3 publications

References 3 publications

A novel EDA variant causing X-linked hypohidrotic ectodermal dysplasia: Case report

A novel EDA variant causing X-linked hypohidrotic ectodermal dysplasia: Case report

On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability

Preimplantation Genetic Diagnosis of Neurodegenerative Diseases: Review of Methodologies and Report of Our Experience as a Regional Reference Laboratory

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