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MAD1L1 and MAD2L1 genes variants in spontaneous miscarriage with aneuploidy.

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Τίτλος: MAD1L1 and MAD2L1 genes variants in spontaneous miscarriage with aneuploidy.
Συγγραφείς: Hosseini N; Department of Molecular Genetics, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran., Kariminejad R; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Boroujeni PB; Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran., Amiri-Yekta A; Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran., Bazrgar M; Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. bazrgar.masood76@gmail.com.
Πηγή: Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology [Chromosome Res] 2026 Aug 03; Vol. 34 (1). Date of Electronic Publication: 2026 Aug 03.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Kluwer Academic Publishers Country of Publication: Netherlands NLM ID: 9313452 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-6849 (Electronic) Linking ISSN: 09673849 NLM ISO Abbreviation: Chromosome Res Subsets: MEDLINE
Imprint Name(s): Publication: Dordrecht : Kluwer Academic Publishers
Original Publication: Oxford, UK : Rapid Communications of Oxford, c1993-
Ιατρικοί όροι (MeSH): Mad2 Proteins*/genetics , Nuclear Proteins*/genetics , Cell Cycle Proteins*/genetics , Abortion, Spontaneous*/genetics , Aneuploidy*, Humans ; Female ; Polymorphism, Single Nucleotide ; Pregnancy ; Adult ; Comparative Genomic Hybridization ; Gene Frequency ; Exons ; Iran
Περίληψη: Aneuploidy accounts for over 57% of spontaneous abortions and occurs even in women of young reproductive age. Despite its major role in pregnancy loss, the genetic basis of fetal aneuploidy remains poorly characterized. This study evaluated the association of MAD1L1 and MAD2L1, two key spindle assembly checkpoint genes, with fetal aneuploidy in women younger than 36 years. Forty aborted fetuses with approved aneuploidy using array comparative genomic hybridization were enrolled in genotyping. The rs121908981 and rs121908982 pathogenic single nucleotide variants (SNVs) of exons 4 and 18 of MAD1L1 and all exons of MAD2L1 were studied in aneuploid fetuses using Sanger sequencing. Identified variants were classified based on ACMG guideline and their frequencies were compared with ethnically matched Iranome database. The effect of SNVs was predicted using the PredictSNP Webtool and Mobidetails database. No targeted pathogenic SNVs were identified in MAD1L1; however, nine other SNVs were detected. Among these, the rare Iranome variants rs1639921 and rs1481591257 were observed in the homozygous state in four and one POCs, respectively, and showed significantly different frequencies compared with Iranome (P < 0.005). The frequency of the deleterious MAD2L1 variant rs903147 did not differ from Iranome, although 15 POCs were homozygous for this variant. In addition, a novel 60-bp deletion in intron 4 of MAD1L1 was identified for the first time. Although more frequent in POCs, its frequency did not differ significantly from that in karyotypically normal controls. Collectively, the rare variants rs1639921 and rs1481591257 may be associated with aneuploidy in POCs.
(© 2026. The Author(s), under exclusive licence to Springer Nature B.V.)
Competing Interests: Declarations. Conflicts of interest: The authors have declared that they have no conflict of interest. Ethics approval: This study was approved by the Institutional Ethics Committee number (IR.ACECR.ROYAN.REC.1397.051). Consent to participate: Written informed consent was obtained from all couples before participating in this study. Consent for publication: The participants provided consent to the use and publication of their anonymized data for this research.
References: Adv Cancer Res. 2011;112:43-75. (PMID: 21925301)
J BUON. 2020 Sep-Oct;25(5):2141-2143. (PMID: 33277827)
Oncogene. 2018 Feb 22;37(8):1020-1030. (PMID: 29084208)
Development. 2013 Sep;140(18):3719-30. (PMID: 23981655)
Nature. 2004 Aug 12;430(7001):797-802. (PMID: 15306814)
Cancer Res. 2016 Jun 1;76(11):3364-75. (PMID: 27197202)
Mol Hum Reprod. 2011 Jan;17(1):14-21. (PMID: 20643875)
Oncogene. 2001 May 31;20(25):3301-5. (PMID: 11423979)
PLoS One. 2011;6(6):e21557. (PMID: 21720555)
Cancer Genet Cytogenet. 1996 Jun;88(2):95-102. (PMID: 8640734)
Mol Cytogenet. 2014 Jun 05;7:38. (PMID: 24976865)
Am J Obstet Gynecol. 2026 Feb;234(2):582. (PMID: 41372005)
Nat Rev Mol Cell Biol. 2007 May;8(5):379-93. (PMID: 17426725)
Fertil Steril. 2015 Dec;104(6):1460-66.e1-12. (PMID: 26361205)
Mol Hum Reprod. 2012 Nov;18(11):554-62. (PMID: 22869558)
Front Genet. 2023 Mar 16;14:1105184. (PMID: 37007941)
Cell Motil Cytoskeleton. 2005 Jul;61(3):145-60. (PMID: 15887295)
Contributed Indexing: Keywords: MAD1L1; MAD2L1; Aneuploidy; Miscarriage; Single Nucleotide Variation (SNV)
Substance Nomenclature: 0 (Mad2 Proteins)
0 (MAD2L1 protein, human)
0 (Nuclear Proteins)
0 (Cell Cycle Proteins)
0 (MAD1L1 protein, human)
Entry Date(s): Date Created: 20260803 Date Completed: 20260803 Latest Revision: 20261008
Update Code: 20261008
DOI: 10.1007/s10577-026-09810-9
PMID: 42545408
Βάση Δεδομένων: MEDLINE
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Aneuploidy accounts for over 57% of spontaneous abortions and occurs even in women of young reproductive age. Despite its major role in pregnancy loss, the genetic basis of fetal aneuploidy remains poorly characterized. This study evaluated the association of MAD1L1 and MAD2L1, two key spindle assembly checkpoint genes, with fetal aneuploidy in women younger than 36 years. Forty aborted fetuses with approved aneuploidy using array comparative genomic hybridization were enrolled in genotyping. The rs121908981 and rs121908982 pathogenic single nucleotide variants (SNVs) of exons 4 and 18 of MAD1L1 and all exons of MAD2L1 were studied in aneuploid fetuses using Sanger sequencing. Identified variants were classified based on ACMG guideline and their frequencies were compared with ethnically matched Iranome database. The effect of SNVs was predicted using the PredictSNP Webtool and Mobidetails database. No targeted pathogenic SNVs were identified in MAD1L1; however, nine other SNVs were detected. Among these, the rare Iranome variants rs1639921 and rs1481591257 were observed in the homozygous state in four and one POCs, respectively, and showed significantly different frequencies compared with Iranome (P &amp;lt; 0.005). The frequency of the deleterious MAD2L1 variant rs903147 did not differ from Iranome, although 15 POCs were homozygous for this variant. In addition, a novel 60-bp deletion in intron 4 of MAD1L1 was identified for the first time. Although more frequent in POCs, its frequency did not differ significantly from that in karyotypically normal controls. Collectively, the rare variants rs1639921 and rs1481591257 may be associated with aneuploidy in POCs.&lt;br /&gt; (&#169; 2026. The Author(s), under exclusive licence to Springer Nature B.V.)
– Name: Abstract
  Label: Competing Interests
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  Data: Declarations. Conflicts of interest: The authors have declared that they have no conflict of interest. Ethics approval: This study was approved by the Institutional Ethics Committee number (IR.ACECR.ROYAN.REC.1397.051). Consent to participate: Written informed consent was obtained from all couples before participating in this study. Consent for publication: The participants provided consent to the use and publication of their anonymized data for this research.
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  Label: References
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  Data: Adv Cancer Res. 2011;112:43-75. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2221925301%22&quot;&gt;21925301)&lt;/searchLink&gt;&lt;br /&gt;J BUON. 2020 Sep-Oct;25(5):2141-2143. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2233277827%22&quot;&gt;33277827)&lt;/searchLink&gt;&lt;br /&gt;Oncogene. 2018 Feb 22;37(8):1020-1030. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2229084208%22&quot;&gt;29084208)&lt;/searchLink&gt;&lt;br /&gt;Development. 2013 Sep;140(18):3719-30. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2223981655%22&quot;&gt;23981655)&lt;/searchLink&gt;&lt;br /&gt;Nature. 2004 Aug 12;430(7001):797-802. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2215306814%22&quot;&gt;15306814)&lt;/searchLink&gt;&lt;br /&gt;Cancer Res. 2016 Jun 1;76(11):3364-75. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2227197202%22&quot;&gt;27197202)&lt;/searchLink&gt;&lt;br /&gt;Mol Hum Reprod. 2011 Jan;17(1):14-21. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2220643875%22&quot;&gt;20643875)&lt;/searchLink&gt;&lt;br /&gt;Oncogene. 2001 May 31;20(25):3301-5. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2211423979%22&quot;&gt;11423979)&lt;/searchLink&gt;&lt;br /&gt;PLoS One. 2011;6(6):e21557. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2221720555%22&quot;&gt;21720555)&lt;/searchLink&gt;&lt;br /&gt;Cancer Genet Cytogenet. 1996 Jun;88(2):95-102. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%228640734%22&quot;&gt;8640734)&lt;/searchLink&gt;&lt;br /&gt;Mol Cytogenet. 2014 Jun 05;7:38. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2224976865%22&quot;&gt;24976865)&lt;/searchLink&gt;&lt;br /&gt;Am J Obstet Gynecol. 2026 Feb;234(2):582. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2241372005%22&quot;&gt;41372005)&lt;/searchLink&gt;&lt;br /&gt;Nat Rev Mol Cell Biol. 2007 May;8(5):379-93. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2217426725%22&quot;&gt;17426725)&lt;/searchLink&gt;&lt;br /&gt;Fertil Steril. 2015 Dec;104(6):1460-66.e1-12. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2226361205%22&quot;&gt;26361205)&lt;/searchLink&gt;&lt;br /&gt;Mol Hum Reprod. 2012 Nov;18(11):554-62. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2222869558%22&quot;&gt;22869558)&lt;/searchLink&gt;&lt;br /&gt;Front Genet. 2023 Mar 16;14:1105184. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2237007941%22&quot;&gt;37007941)&lt;/searchLink&gt;&lt;br /&gt;Cell Motil Cytoskeleton. 2005 Jul;61(3):145-60. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2215887295%22&quot;&gt;15887295)&lt;/searchLink&gt;
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        Type: general
      – SubjectFull: Female
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