Paternal Transmission of Small Supernumerary Marker Chromosome 15 Identified in Prenatal Diagnosis Due to Advanced Maternal Age

The detection of supernumerary marker chromosomes (SMCs) in prenatal diagnosis is always a challenge. In this study, we report a paternally inherited case of a small SMC(15) that was identified in prenatal diagnosis due to advanced maternal age. A 39-year-old woman underwent amniocentesis at 16 weeks of gestation. A fetal abnormal karyotype − 47,XX,+mar − with one sSMC was detected in all metaphases. Since this sSMC was critical in the parental decision to continue or interrupt this pregnancy, we proceeded to study the fetus and their parents. Cytogenetic and molecular analyses revealed a fetal karyotype 47,XX,+mar pat.ish idic(15)(ql2)(D15Zl++,SNRPN−-), in which the sSMC(15) was a paternally inherited inverted duplicated chromosome and did not contain the critical region of Prader–Willi/Angelman syndromes. Moreover, fetal uniparental disomy was excluded. Based on this information and normal obstetric ultrasounds, the parents decided to proceed with the pregnancy and a phenotypically normal girl was born at 39 weeks of gestation. In conclusion, the clinical effects of sSMCs need to be investigated, especially when sSMCs are encountered at prenatal diagnosis. Here, although the paternal sSMC(15) was not associated with an abnormal phenotype, its characterization allows more accurate genetic counseling for the family progeny.

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Prenatal diagnosis of a 16p11.2p11.1 mosaic small supernumerary marker chromosome (sSMC)

10.21203/rs.2.19367/v1 ◽

2019 ◽

Author(s):

Zsolt Tidrenczel ◽

Erika P Tardy ◽

Henrietta Pikó ◽

Edina Sarkadi ◽

Ildikó Böjtös ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Maternal Age ◽

Marker Chromosome ◽

Advanced Maternal Age ◽

Autism Spectrum ◽

Comparative Genome Hybridization ◽

Snp Analysis ◽

Molecular Cytogenetic ◽

Small Supernumerary Marker Chromosome

Abstract Background. Small supernumerary marker chromosome (sSMC) is a challenge in prenatal diagnosis. Its’ presence is associated with advanced maternal age and distinct ultrasound findings, prediction of postnatal clinical consequences and prenatal counselling is difficult. Exact characterization of an sSMC is augmented by the application of novel molecular methods such as fluorescent in situ hybridization (FISH) and array comparative genome hybridization (aCGH). Case presentation. Chorion villous sampling of a fetus of a 42-year old secundipara was carried out due to advanced maternal age and the conventional banding cytogenetic examination revealed a mosaic sSMC. Detailed prenatal ultrasound scan showed no fetal malformations. The karyotype from confirmatory amniocentesis was 47,XY,+mar[45]/46,XY. The level of mosaicism was 70% from chorionic villus and amnion cells as well. By using FISH and SNP based aCGH the exact origin of the marker was described and the final prenatal karyotype was determined as 47,XY,+mar[70].arr[GRCh38]16p11.2p11.1(31699804_35989873)x3dn/46,XY[30]. The increase in DNA dosage was 4,29 Mb affecting 20 genes with two OMIM ones (ZNF267 and TP53TG3), the SNP analysis excluded the possibility of uniparental disomy (UPD) of the chromosome. The application of the molecular cytogenetic methods allowed us the differentiate the mosaic marker chromosome from the known 16p11.2 duplication syndrome in close neighboring that is connected to developmental delay and autism spectrum disorder. The present case was identified as a harmless de novo euchromatic variant (EV) of the short arm of chromosome 16. Postnatal karyotyping from neonatal peripheral blood confirmed the presence of the marker. FISH analysis with probe D16Z2 on cultured lymphocyte and buccal smear samples revealed a 64% and 45% mosaic state of the sSMC, respectively. The precise karyotype was finally defined as 47,XY,+min(16)(:16p11.2->p11.1:)dn[64]/46,XY. Conclusions. Novel microarray methods combined with molecular cytogenetic analysis is particularly effective in the rapid and accurate diagnosis of sSMCs, especially in a prenatal situation when the exact characterization of a genomic imbalance is of utmost importance. Precise diagnosis facilitates proper genetic counseling, allows informed decision making and helps avoiding unnecessary pregnancy termination.

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Presumed mutation in a microsatellite marker mimicking segmental uniparental disomy in a case of a small supernumerary marker chromosome detected at prenatal diagnosis

Clinical Genetics ◽

10.1034/j.1399-0004.2003.00102.x ◽

2003 ◽

Vol 64 (2) ◽

pp. 168-171 ◽

Cited By ~ 4

Keyword(s):

Prenatal Diagnosis ◽

Microsatellite Marker ◽

Marker Chromosome ◽

Uniparental Disomy ◽

Small Supernumerary Marker Chromosome

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Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 15

Taiwanese Journal of Obstetrics and Gynecology ◽

10.1016/j.tjog.2013.12.004 ◽

2014 ◽

Vol 53 (1) ◽

pp. 129-132 ◽

Cited By ~ 2

Author(s):

Chih-Ping Chen ◽

Ming Chen ◽

Yi-Ning Su ◽

Schu-Rern Chern ◽

Peih-Shan Wu ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Marker Chromosome ◽

Chromosome 15 ◽

Molecular Cytogenetic ◽

Small Supernumerary Marker Chromosome ◽

Cytogenetic Characterization

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Effect of chorionic villus sampling on utilization of prenatal diagnosis in women of advanced maternal age

Clinical Genetics ◽

10.1111/j.1399-0004.1992.tb03673.x ◽

2008 ◽

Vol 41 (5) ◽

pp. 239-242 ◽

Cited By ~ 5

Author(s):

Helen Brandenburg ◽

Coon G. Gho ◽

Milena G. J. Jahoda ◽

Theo Stijnen ◽

Hans Bakker ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Maternal Age ◽

Chorionic Villus ◽

Advanced Maternal Age ◽

Chorionic Villus Sampling

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A New Case of Prenatally Diagnosed Pentasomy X: Review of the Literature

Case Reports in Obstetrics and Gynecology ◽

10.1155/2015/935202 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Linda Maria Azzurra Pirollo ◽

Leila Baghernajad Salehi ◽

Simona Sarta ◽

Marco Cassone ◽

Maria Vittoria Capogna ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Maternal Age ◽

Three Dimensional ◽

Advanced Maternal Age ◽

Fetal Autopsy ◽

X Ray ◽

Y Chromosomes ◽

Increased Risk ◽

Prenatal Test ◽

Mother’S Age

Pentasomy X is a rare chromosomal abnormality probably due to a nondisjunction during the meiosis. Only four cases prenatally diagnosed were described until now. Our case is the fifth one prenatally diagnosed at 20 weeks of gestational age in a 39-years-old woman. She underwent invasive prenatal diagnosis for her advanced maternal age without any other known risk factor. Amniocentesis performed at 17 weeks showed a female 49, XXXXX karyotype. The ultrasonographic examination revealed nonspecific signs of a mild early fetal growth retardation and no significant increased nuchal fold. The fetal autopsy and the X-ray excluded major malformations. Prenatal diagnosis is often difficult due to the lack of indicative ultrasonographic findings and the rarity of described cases. The influence of the mother’s age on the occurrence of penta-X syndrome has not been determined. Considering the lack of correlation between advanced maternal age and increased risk for pentasomy X, as well as the absence of typical echographic signs, evaluation of the inclusion of a noninvasive prenatal test (NIPT) that expands clinical coverage to include the X and Y chromosomes in routine prenatal diagnosis should be considered as well as three-dimensional ultrasound to detect any helpful indicative prognostic signs.

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