<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec>
<h3>Objective</h3>
<p>Pathogenic variations of the <italic>NLRP7</italic> and <italic>KHDC3L</italic> genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon that can lead to severe comorbidities. Little is known about the diversity of genetic defects or the natural course of disease progression among recurrent hydatidiform mole cases from distinct ethnicities. In this study, we aimed to investigate the mutation profile and pregnancy outcomes in patients with multiple molar pregnancies.</p>
</sec>
<sec>
<h3>Material and Methods</h3>
<p>Three unrelated cases with recurrent molar pregnancies are included in this study. None of the patients had a known family history of molar pregnancy. Clinical findings and follow-up results are documented. Sanger sequencing is used to reveal genetic defects in exons and exon-intron boundaries of <italic>NLRP7</italic> and <italic>KHDC3L</italic> genes.</p>
</sec>
<sec>
<h3>Results</h3>
<p><italic>NLRP7</italic> pathogenic variants were found in all three cases. In two cases, homozygous, c.2471+1G>A canonical splice cite variant was identified and in one case a homozygous, c.2571dupC (p.Ile858HisfsTer11) frameshift variant was identified. No variant in the <italic>KHDC3L</italic> gene was found in any case. In all cases, the development of gestational trophoblastic neoplasia complicated the clinical course and the treatment plans.</p>
</sec>
<sec>
<h3>Conclusions</h3>
<p>We found that defects of the <italic>NLRP7</italic> gene are principally responsible for etiology in our region, and the mutation profile suggests a founder effect in the Turkish population. We suggest early genetic diagnosis and counseling in molar pregnancies and recommend close follow-up in terms of conversion to gestational trophoblastic neoplasia.</p>
</sec>
</abstract>

Objective
Pathogenic variations of the NLRP7 and KHDC3L genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon that can lead to severe comorbidities. Little is known about the diversity of genetic defects or the natural course of disease progression among recurrent hydatidiform mole cases from distinct ethnicities. In this study, we aimed to investigate the mutation profile and pregnancy outcomes in patients with multiple molar pregnancies.


Material and Methods
Three unrelated cases with recurrent molar pregnancies are included in this study. None of the patients had a known family history of molar pregnancy. Clinical findings and follow-up results are documented. Sanger sequencing is used to reveal genetic defects in exons and exon-intron boundaries of NLRP7 and KHDC3L genes.


Results
NLRP7 pathogenic variants were found in all three cases. In two cases, homozygous, c.2471+1G>A canonical splice cite variant was identified and in one case a homozygous, c.2571dupC (p.Ile858HisfsTer11) frameshift variant was identified. No variant in the KHDC3L gene was found in any case. In all cases, the development of gestational trophoblastic neoplasia complicated the clinical course and the treatment plans.


Conclusions
We found that defects of the NLRP7 gene are principally responsible for etiology in our region, and the mutation profile suggests a founder effect in the Turkish population. We suggest early genetic diagnosis and counseling in molar pregnancies and recommend close follow-up in terms of conversion to gestational trophoblastic neoplasia.

High Risk of Gestational Trophoblastic Neoplasia Development in Recurrent Hydatidiform Moles with <italic>NLRP7</italic> Pathogenic Variations

Faculty of Medicine, Dokuz Eylul University

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

High Risk of Gestational Trophoblastic Neoplasia Development in Recurrent Hydatidiform Moles with  Pathogenic Variations

Objective
Pathogenic variations of the NLRP7 and KHDC3L genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon...

Sequence of the primers (5’→3’) used for the mutation analysis of KHDC3L
Exon	5’ Primer (Forward)	3’ Primer (Reverse)
1	GTTCCTCCTACCGGGTGCG	CGATCCTCACCAGTAGCCAAT
2	GGCTTCTTTCTGCCACCCATA	TCTCCGGTGGAGGTGCAG
3	GCTGGGAATAGGGCTACCTG	GTGGCGAGGAAGGATGATGT

Sequence of the primers (5’→3’) used for the mutation analysis of NLRP7
Exon	5’ Primer (Forward)	3’ Primer (Reverse)
1	UTR – not amplified	UTR – not amplified
2	TCTTGGCACACAGGAAACTG	TGTAAGGCTGGAGTGCAGTG
3	CATGCCTGGCTGACACTTTA	TCTGCTCATTGCAACCTCTG
4 - part 1	CTCAAGTGATCCACCCACCT	AGGAAGATGTTACCCAGGGC
4 - part 2	GGCCTTGATGAGCTGAAAGT	CCTCAGCTTCCAGCAGTTTC
4 - part 3	CTGTTCCTGGACGGAGACAT	TGTCAGAATTTCCCTCTGGC
5	TTGTGGTTTTTGCCATTGAA	AGGAAGACCCTGAACGATGA
6	CCCGGCCAAGAACTTCTAAT	GTAACCACTCCAGATGCCGT
7	AGGCTGCAGTGAGGTGAGAT	AACACCTGACTTACTGCGCC
8	GATGAACAGGAAGGGCTGAA	GCACATGAATTCAAGCAGGA
9	GCAAGCCCACCTGGAAGTAT	AGTGTTTGGAAATCTGGAAATCC
10	CTCCCGAAGTGTTGGGATTA	ACCTCTGCCTCTCAGGTTCA
11	GGCATCCTGGGTAGTTGAGA	TTTTTGGGAGATTCTGCACG

High Risk of Gestational Trophoblastic Neoplasia Development in Recurrent Hydatidiform Moles with NLRP7 Pathogenic Variations

Article Category: ORIGINAL ARTICLE

Data publikacji: 02 maj 2023

Zakres stron: 45 - 50

DOI: https://doi.org/10.2478/bjmg-2022-0025

© 2022 Kocabey M. et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1.

Figure 2.

Amplification and sequencing primers of NLRP7 and KHDC3L genes