We report a case of familial small supernumerary marker chromosome 15 in a phenotypically normal female with 4 recurrent spontaneous abortions and a healthy child. The initial karyotype showed a small, bisatellited, apparently metacentric marker chromosome, 47,XX,+idic(15)(q11.1), maternally inherited. The proband's mother was mosaic for the idic(15)(q11.1) without pregnancy loss. Reexamination of the proband's karyotype revealed cryptic mosaicism for 1 ring and 1 minute chromosome derived de novo from chromosome 9 in 2% of the metaphases. In FISH analysis, the patient's karyotype was mos 47,XX,+idic(15)(q11.1)mat[100]/49,XX,+idic(15)(q11.1)mat,+r(9;9;9;9),+der(9)dn[2]. The second spontaneous abortion had trisomy 9 (47,XX,+9); the third had mosaic trisomy 9 in 21% of the nuclei and isodicentric chromosome 15 in 36% of the nuclei (mos 48,XN,+9,+idic(15)(q11.1)/47,XN,+9/47,XN,+idic(15)(q11.1)/46,XN). The first and fourth abortions were not cytogenetically studied. The cause of the spontaneous abortions in this patient is likely the cryptic mosaicism for ring and minute chromosomes 9, and gonadal mosaicism is most probable, due to the 2 abortions.

Keywords:
Cryptic mosaicism, Recurrent pregnancy loss, Small supernumerary marker chromosomes
1.
Al-Buhtori M, Moore L, Benbow EW, Cooper RJ: Viral detection in hydrops fetalis, spontaneous abortion, and unexplained fetal death in utero. J Med Virol 83:679-684 (2011).
2.
Armanet N, Tosca L, Brisset S, Liehr T, Tachdjian G: Small supernumerary marker chromosomes in human infertility. Cytogenet Genome Res 146:100-108 (2015).
3.
Dalprà L, Giardino D, Finelli P, Corti C, Valtorta C, et al: Cytogenetic and molecular evaluation of 241 small supernumerary marker chromosomes: cooperative study of 19 Italian laboratories. Genet Med 7:620-625 (2005).
4.
Ewers E, Yoda K, Hamid AB, Weise A, Manvelyan M, Liehr T: Centromere activity in dicentric small supernumerary marker chromosomes. Chromosome Res 18:555-562 (2010).
5.
Franssen MT, Musters AM, van der Veen F, Repping S, Leschot NJ, et al: Reproductive outcome after PGD in couples with recurrent miscarriage carrying a structural chromosome abnormality: a systematic review. Hum Reprod Update 17:467-475 (2011).
6.
Gruhne B, Sompallae R, Marescotti D, Kamranvar SA, Gastaldello S, Masucci MG: The Epstein-Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species. Proc Natl Acad Sci USA 106:2313-2318 (2009).
7.
Lebedev I: Mosaic aneuploidy in early fetal losses. Cytogenet Genome Res 133:169-183 (2011).
8.
Liehr T: Familial small supernumerary marker chromosomes are predominantly inherited via the maternal line. Genet Med 8:459-462 (2006).
9.
Liehr T: Small Supernumerary Marker Chromosomes (sSMC): A Guide for Human Geneticists and Clinicians (Springer, Heidelberg 2012).
10.
Liehr T: Small supernumerary marker chromosomes detected in connection with infertility. Zhonghua Nan Ke Xue 20:771-780 (2014).
11.
Maithripala S, Durland U, Havelock J, Kashyap S, Hitkari J, et al: Prevalence and treatment choices for couples with recurrent pregnancy loss due to structural chromosomal anomalies. J Obstet Gynaecol Can 40:655-662 (2018).
12.
Manvelyan M, Riegel M, Santos M, Fuster C, Pellestor F, et al: Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: detailed molecular cytogenetic characterization and review of the literature. Int J Mol Med 21:705-714 (2008).
13.
Nikitina TV, Sazhenova EA, Sukhanova NN, Lebedev IN, Nazarenko SA: Evaluation of the role of uniparental disomy in early embryolethality of man (in Russian). Ontogenez 35:297-306 (2004).
14.
Nikitina TV, Sazhenova EA, Tolmacheva EN, Sukhanova NN, Kashevarova AA, et al: Comparative cytogenetic analysis of spontaneous abortions in recurrent and sporadic pregnancy losses. Biomed Hub 1:446099 (2016).
15.
Pristyazhnyuk IE, Menzorov AG: Ring chromosomes: from formation to clinical potential. Protoplasma 255:439-449 (2018).
16.
Santos M, Mrasek K, Rigola MA, Starke H, Liehr T, Fuster C: Identification of a “cryptic mosaicism” involving at least four different small supernumerary marker chromosomes derived from chromosome 9 in a woman without reproductive success. Fertil Steril 88:969.e11-969.e17 (2007).
17.
Starke H, Nietzel A, Weise A, Heller A, Mrasek K, et al: Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification. Hum Genet 114:51-67 (2003).
© 2018 S. Karger AG, Basel
2018
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.