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Received: 11 February 2019    Revised: 29 June 2019    Accepted: 11 July 2019

DOI: 10.1111/aogs.13694

ORIGINAL RESEARCH ARTICLE

Evidence for the Oocyte Mosaicism Selection model on the

origin of Patau syndrome (trisomy 13)

Lilla É. Babay1  | Dániel Horányi2 | Balázs Győrffy3,4 | Gyula R. Nagy5

1
Department of Obstetrics and
Gynecology, Uzsoki Hospital, Budapest, Abstract
Hungary Introduction: In 2008, Hultén et al hypothesized that maternal ovarian trisomy 21
2
Department of Obstetrics and
mosaicism might be the primary causative factor for fetal Down syndrome. We hy‐
Gynecology, Péterffy Sándor Street
Hospital, Clinic and Trauma Center, pothesize that this theory can be extended to trisomy 13.
Budapest, Hungary
Material and methods: We collected fetal ovarian tissue from seven female fetuses
3
MTA TTK Lendület Cancer Biomarker
Research Group, Budapest, Hungary
between 16 and 23 gestational weeks, following the termination of the pregnancy
4
2nd Department of Pediatrics, Semmelweis for non‐genetic reasons. All procedures were performed with informed consent and
University, Budapest, Hungary ethical approval from the local ethics committee. We used touch preparation tech‐
5
Baross Street Division, Department of
niques from fetal ovarian tissues and an anti‐stromal antigen 3 antibody against
Obstetrics and Gynecology, Semmelweis
University, Budapest, Hungary the meiosis‐specific stromal antigen 3 protein to differentiate between germ cells,
ovarian stromal cells and the cells entering their first meiotic prophase. We used
Correspondence
Lilla É. Babay, Department of Obstetrics and fluorescence in situ hybridization analysis to determine chromosome 13 numbers
Gynecology, Uzsoki Hospital, 29‐41
in each cell.
Uzsoki u., Budapest 1145, Hungary.
Email: lilla.babay@gmail.com Results: We were able to detect a proportion of trisomy 13 cells in all cases. The
average incidence of trisomy 13 cells was 2.04% in stromal antigen 3‐positive and
0.91% in the stromal antigen 3‐negative cells. The number of the trisomic cells in‐
creased significantly with gestational age (for stromal antigen 3‐positive cells r = 0.93,
P = 0.0038, for stromal antigen 3‐negative cells r = 0.85, P = 0.0071).
Conclusions: This study indicates that besides trisomy 21, the Oocyte Mosaicism
Selection model could be extended to trisomy 13 as well. The crucial factor for trisomy
13 seems to be the pre‐meiotic/mitotic trisomy 13 mosaicism, leading to a so‐called sec‐
ondary meiotic nondisjunction of those oocytes having three copies of chromosome 13.

KEYWORDS
aneuploidy, meiosis, oocyte, Oocyte Mosaicism theory, STAG3, trisomy

1 | I NTRO D U C TI O N
Patau syndrome is a clinically severe condition first described by
Patau et al1 in 1960. It is one of the most common human triso‐
2
mies, occurring in .18% of all clinically detected pregnancies ; the
prevalence is 1:5000. It is associated with mental and growth re‐
tardations, and heart, nervous, urogenital and various other organ
defects which lead to a limited survival rate: 85% of the patients do
not survive beyond 1 year of life.3 The syndrome can appear in a
complete, partial or mosaic form; the complete form is caused by an
extra chromosome 13.
In the past decades, several theories surfaced aiming to explain
the origin of these extra chromosomes in common trisomies (tri‐
somy 21, 18 and 13). The most widely accepted hypothesis is that
the main problems are meiotic segregation errors of normal disomic
oocytes (meiotic nondisjunction) in senior women. In addition to this

Abbreviations: DAPI4′, 6‐diamidino‐2‐phenylindole; FISH, fluorescence in situ hybridization; PBS, phosphate‐buffered saline; STAG 3, stromal antigen 3; T13, trisomy 13; T21, trisomy 21.

Acta Obstet Gynecol Scand. 2019;00:1–7. © 2019 Nordic Federation of Societies of Obstetrics |  1
wileyonlinelibrary.com/journal/aogs  
and Gynecology
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2       BABAY et al.
conventional hypothesis, interesting new theories have emerged.
In 2008, Hultén et  al4 hypothesized that maternal oocyte trisomy
21 (T21) mosaicism might be the primary causative factor for fetal
Down syndrome. They suggested that instead of the meiotic non‐
disjunction of a normal disomic oocyte, the cause of T21 was an
obligate—so‐called secondary—nondisjunction of T21 oocytes due
to pre‐meiotic mitotic segregation errors. The number of disomic
oocytes then drops faster than the small proportion of trisomic oo‐
cytes.5-8 The maternal age effect seems to be an accumulation of
T21 oocytes in the ovarian reserve of older women due to the delay
of these cells in maturation, which lag behind the normal cells.9,10
Hultén et al4 used fluorescence in situ hybridization (FISH) with two
21 chromosome‐specific probes to determine the copy number of
chromosome 21 in ovarian cells from phenotypically normal fetuses
at 14‐22 gestational weeks. They found that all the detected eight
fetuses had T21 cells not only in meiotic but also in pre‐meiotic mi‐
totic and ovarian mesenchymal cells. This theory may lead to a par‐
adigm shift. The Oocyte Mosaicism Selection model5 might explain
the origin of Down syndrome. In our study, we investigated whether
we could find similar results in the case of another common trisomy
as well. The rationale behind specifically searching for trisomy 13
(T13) among the fetal oocytes was that it is easier in fetuses to
establish the absence of T13 based on normal prenatal ultrasono‐
graphic results, as the majority of fetuses having T13 have abnormal
fetal ultrasonographic findings.11 Some other trisomies (eg, trisomies
16 or 22) are more common but very often cause spontaneous abor‐
tions at early gestational ages. Finding fetal ovaries in these early
abortions is technically challenging and
2 |  M ATE R I A L A N D M E TH O DS
We collected fetal ovarian tissue samples from seven female fetuses
at 16‐23 weeks of gestation, following the termination of the preg‐
nancy for non‐genetic reasons. All procedures were performed with
informed consent and ethical approval from the local ethics commit‐
tee. All the fetuses had a normal phenotypic appearance (we found
no abnormalities either on prenatal ultrasonographic examinations
or at the time of postmortem examinations of these fetuses). We
removed fetal ovaries a few hours after abortion and made slides
from the specimens with touch preparation technique: dabbing the
cut surface of the fetal ovaries onto a microscope slide to distrib‐
ute a thin layer of cells for microscopic examination. The slides were
stored in a refrigerator at +4°C before the immunofluorescence and
FISH examination. In the blinded experiment, the observer did not
know the gestational age of samples.
For the immunofluorescence, we used an anti‐stromal antigen
3 (STAG3) antibody (Cat. No. HPA049106), which can be utilized
against the meiosis‐specific STAG3 protein to differentiate germ
cells and ovarian stromal cells from the cells entering their first mei‐
otic prophase. For the immune reaction, we started with a 10‐minute
formalin wash (neutral buffered, 10%, MDL No. MFCD00003274;
Sigma‐Aldrich Inc., Hungary, Budapest, Nagy Diófa) for fixation and
Key message
Hulten's Oocyte Mosaicism Selection model can be
­extended to trisomy 13. It is appealing to conclude that
oocyte mosaicism can play a major role in the formation
of the most common trisomies, in place of current dogma.
a 5‐minute citrate wash (MDL No. MFCD00150031; Sigma‐Aldrich
Inc.) to remove unwanted proteins. After a 3 × 15‐minute phosphate‐
buffered saline (PBS) (MDL No. MFCD00131855; Sigma‐Aldrich Inc.)
wash, we blocked the samples by soaking for 45 minutes in 5% bovine
serum albumin/PBS solution in a dark chamber. After 2 × 4 minutes
of a PBS wash, we started the first phase of the immune reaction
with 100× dilution in 1% bovine serum albumin/PBS solution, cov‐
ered with parafilm, in a dark humidity chamber at +4°C for 12 hours.
After a 3 × 5 minutes PBS wash, the secondary antibody was applied
in a 2.5 mL/400 mL 1× PBS dilution. We finished the reaction with a
3 × 5‐minute PBS wash, mounting with Vectashield antifade mounting
medium for immunofluorescence with 4′,6‐diamidino‐2‐phenylindole
(DAPI; Cat. No: H‐1200; Vector Laboratories Inc., Orton Southgate,
Peterborough, UK).
For the second step FISH analysis, the same slides were fixed in
methanol‐acetic acid as were washed in standard saline citrate two
times and digested with pepsin (CAS‐No. 9001‐75‐6; Sigma‐Aldrich
Inc.). For the hybridization, we used two DNA probes positioned
near the end (Vysis LSI (13q14) Spectrum Green Probe; Abbott
Molecular Inc., Hungary, Budapest, Árpád fejedelem útja) and near
to the centromere (Vysis LSI (13q34) Spectrum Orange Probe;
Abbott Molecular Inc.) of the chromosome 13, according to the
manufacturer's instructions; this FISH technique is routinely applied
in this laboratory. After the immune and FISH reactions, the slides
were stained with DAPI (Cat. No. 62248; Thermo Fisher Scientific
Inc., Hungary, Budapest, Repülőtéri út).
We used stringent criteria to establish the numbers of chromo‐
some 13 in the analyzed cells. Only cells with three clear double flu‐
orescent signals (3 green and 3 red) were counted as trisomies; those
showing two double signals (2 green and 2 red) were scored as nor‐
mal disomies. We excluded other combinations of signals because of
the likelihood of them being artificial.
We detected fluorescent signals with a Nikon Eclipse E600 mi‐
croscope, and a Jenoptik CCD camera captured the colored images.
We analyzed the images with a CaseViewer program (3DHystec Inc.,
Hungary, Budapest, Öv u). CaseViewer is a digital microscope appli‐
cation designed to support the histopathological diagnostic work‐
flow and the microscope examination process. The same slides with
different staining can be organized and then aligned. The applica‐
tion is useful for investigating the same slide stained by different
markers. The digital microscope application allowed the comparison
of the immune reactions with the FISH reactions performed on the
same slide. The goal was to analyze 1000 STAG3‐positive and 1000
STAG3‐negative cells from all samples.
BABAY et al.
To have a control population and to test the effectiveness of the
immune hybridization and the dual FISH probe analysis, we applied the
same procedure to preparations of blood lymphocytes obtained from
subjects without aneuploidies. Spearman rank correlation was com‐
puted to compare continuous variables. Statistical significance was set
at P < 0.05. The sample analysis pipeline is summarized in Figure 1.
Ethics approval
The study was approved by the Hungarian Medical Research Council
Scientific and Research Ethics Committee; reference number
5419/2013/EKU.
3 | R E S U LT S
STAG3 antibody allowed differentiation between germ cells entering
meiosis (STAG3‐positive), pre‐meiotic germ cells, and ovarian stroma
cells (both STAG3‐negative) (Figure 2). Using FISH with two specific
probes for chromosome 13, we detected a proportion of T13 cells in
all seven phenotypically normal female fetuses (Figure 3). We ana‐
lyzed 1000 STAG3‐positive and 1000 STAG3‐negative cells in all but
one of the seven fetuses. (We investigated on average 916 STAG3‐
positive and 928 STAG3‐negative cells). In the case where we did
not find a sufficient number of samples (and were able to analyze
500 cells), presumably the fetal ovarian underdevelopment was re‐
sponsible. We were able to detect a proportion of T13 cells in all
cases. The average incidence of T13 cells was 2.04% in STAG3‐posi‐
tive cells (range .8‐3.0%) and .91% in the STAG3‐negative cells (range
0.4‐1.5%). The number of the trisomic cells increased significantly
with gestational age (for STAG3‐positive cells r = 0.93, P = 0.0038,
for STAG3‐negative cells r = 0.85, P = 0.0071) (Table 1, Figure 4).
Collect the sample:
ovarian tissue samples from 7 female fetuses (gestational age: 16-23 wk)
F I G U R E 1   Flowchart of the research.
Preparate the sample:
The main steps of the process are: touch preparation technique (store at +4°C)
the ovarian sample collecting from 7
female fetuses, the sample preparation
by touch preparation technique, the
differentiation of the meiotic prophase and stromal cells:
germ cells from the pre‐meiotic germ
cells and stromal cells by the STAG3
immunofluorescence antibody, the
identification of chromosome 13 with
FISH analysis performed on the same
slide, and the searching process for
trisomy 13 in STAG3‐positive and
STAG3‐negative cells by comparing
results of immunofluorescence and FISH
reaction [Colour figure can be viewed at
wileyonlinelibrary.com]
|
      3
In obtaining the estimate of T13 mosaicism, we excluded cell
nuclei showing any deviation from those with three green signals
together and three red signals, as these might have been artifacts
(Table 2).
We did not find any indication of a similar type of mosaicism in
blood lymphocytes from two adults with normal karyotypes.
4 | D I S CU S S I O N
To explore the origin of Patau syndrome, it is necessary to talk about
the cell division cycles of the oocytes first. In the primordial germ
cells of the embryonic ovaries, as a first step, multiple pre‐meiotic
oogonial mitotic cell divisions take place. Meiosis is the next step,
starting with meiotic prophase I, which begins at around the 9th ges‐
tational week, but further progress is blocked. During the develop‐
ment of the oocyte, the crossover process and chiasma formation
occur prenatally in a fetus, but meiosis as a cell division cycle is quite
long, the final steps occur postnatally at fertilization in adulthood.
In the fertile period of the adult, the first meiotic cell division fin‐
ishes just before ovulation. After prophase II and metaphase II of the
second meiotic cell division, ovulation follows, and then the oocytes
arrest. The second meiotic cell division is completed only after ferti‐
lization. In essence, the meiosis is a long cell division process: it lasts
from mid‐fetal life until menopause.
According to the conservative hypothesis, most common triso‐
mies (eg, T21 and T13) are due to a disturbance occurring during the
prolonged meiotic prophase I,12 leading to the so‐called (primary)
nondisjunction at the first meiotic division, which happens in adult‐
hood just before ovulation. This also associates the trisomic pregnan‐
cies with increased maternal age. It hypothesizes that at increased
maternal ages the meiotic process is less efficient because of the
Mark chromosome 13:
FISH analysis on the same slide
reactions performed on the same side:
Search for trisomy 13 in STAG3 positive and in STAG3 negative cells: Nikon
Eclipse E600 microscope - Jenoptic CCD camera - analysis with CaseViewer
 |
4       BABAY et al.

longer dictyotene stage of meiotic prophase I. There is a reduction in

F I G U R E 2   Example of a STAG3‐positive cell. Meiosis‐specific
STAG3 antibody (green fluorescence) allowed differentiation
between germ cells entering meiosis (STAG3‐positive), pre‐meiotic
germ cells and ovarian stroma cells (both STAG3‐negative showing
a blue pattern) [Colour figure can be viewed at wileyonlinelibrary.
com]
cohesion with the bivalent chromatids and so, in the end, only the chi‐
asma holds the sister chromatids together. The weakened bivalents
may segregate abnormally, which leads to an increase of trisomies.2
In sharp contrast, Hultén et  al5 based their theory on the
Oocyte Mosaicism Selection model: they concluded that the ma‐
jority, if not all cases of T21, are caused not by a problem in the
first meiotic cell division; instead, the crucial factor seems to be
the widespread occurrence of pre‐meiotic/mitotic T21 mosaicism,
leading to a so‐called secondary meiotic nondisjunction of those
oocytes with three chromosomes 21 (Figure 5). This model can
also explain the maternal age effect in trisomies: the trisomic oo‐
cytes may have a delay in maturation, which leads to their accu‐
mulation in the ovaries and it can cause higher trisomic incidence
at advanced maternal ages.
Previously Hultén et  al4 examined fetal ovarian tissues: they
analyzed eight phenotypically normal fetuses and detected oocyte

(A) (B)

F I G U R E 3   Example of comparison of immunofluorescence and FISH results performed on the same slide. (A) Demonstration of the
immunofluorescence reaction: The blue pattern means that the cell is STAG3‐negative, and the green fluorescence reveals the meiosis‐
specific STAG3 protein which can differentiate germ cells and ovarian stromal cells from the cells entering their first meiotic prophase. (B)
Demonstration for the FISH reaction. The green and the red dots are the chromosome‐specific signals: a normal cell nucleus shows two
dual chromosome 13‐specific signals. In this picture, we can observe a T13 nucleus showing three dual chromosome 13‐specific signals. As
a digital microscope application allowed comparison of the immunofluorescence reactions with the FISH reactions performed on the same
slide, we can see that the T13 nucleus (B) is STAG3‐positive (B) [Colour figure can be viewed at wileyonlinelibrary.com]

TA B L E 1   The proportion of T13 cell

T13 cells (%)
nuclei in the examined fetal ovaries
Gestational Meiotic pro- Pre‐meiotic germ cells identified by two chromosome 13‐specific
Case No. age (wk) Total (%) phase germ cells and stroma cells probes. We used the meiosis‐specific
STAG3 protein to differentiate the cells
1. 16 13/2000 (0.65) 8/1000 (0.80) 5/1000 (0.50)
entering their first meiotic prophase from
2. 16 9/1000 (0.90) 7/500 (1.40) 2/500 (0.40) pre‐meiotic germ cells and ovarian stroma
3. 18 29/2000 (1.45) 22/1000 (2.20) 7/1000 (0.70) cells
4. 19 9/1000 (0.90) 0/1000 (0) 9/1000 (0.90)
5. 19 29/2000 (1.45) 18/1000 (1.80) 11/1000 (1.10)
6. 20 42/2000 (2.10) 27/1000 (2.70) 15/1000 (1.50)
7. 23 40/2000 (2.00) 30/1000 (3.00) 10/1000 (1.00)
Average   171/12000 (1.42) 112/5500 (2.04) 59/6500 (0.91)
BABAY et al. |
      5

(A) (B)
0.035 0.016

0.03 0.014

Proportion Stag3 negative

Proportion Stag3 positive

0.012
0.025
0.01
0.02
0.008
0.015
0.006
0.01
0.004
0.005 0.002

0 0
14 16 18 20 22 24 15 17 19 21 23 25
Age Age

F I G U R E 4   Accumulation of T13 oocytes during fetal oogenesis. The graphs show the mean number of (A) STAG3‐positive T13 germ
cells and (B) STAG3‐negative T13 germ cells and stromal cells scored in samples of fetal ovaries. Note that the number of T13 cells was
significantly increased with gestational age for both STAG3‐positive and STAG3‐negative cells, respectively r = 0.93, P = 0.0038 and r = 0.85,
P = 0.0071 [Colour figure can be viewed at wileyonlinelibrary.com]

TA B L E 2   Number of FISH signals per chromosome in ovarian cells from seven female fetuses. For chromosome 13 the presence of six
signals would indicate a trisomy identified by two chromosome 13‐specific probes. Cell nuclei with 2 signals were considered either false‐
negative monosomy 13 (due to the pairing of the two chromosomes 13) or true monosomy 13; nuclei with 3 or 5 signals are likely false‐
negative or false‐positive signals. (Green: Vysis LSI [13q14], Red: Vysis LSI [13q34])

Number of signals

Chromosome Number of cells 2 green/2 red 3 green/3 red 1 green/1 red 3 signals 5 signals

13 12 000 11 416 171 35 168 210

mosaicism with trisomy 21 in 0.20‐0.88% of cells. They examined an
average of 913 STAG3‐positive and 531 STAG3‐negative cells per
case, and the average incidence of T21 trisomies was 0.66% in meiotic
prophase germ cells and 0.80% in pre‐meiotic germ cells. The aver‐
age gestational age in the analyzed samples was 17.25  weeks. For
the control process, they collected blood lymphocytes from three
children with T21 and three other children, shown to have normal
karyotypes by metaphase analysis.
Some question the Oocyte Mosaicism Selection model. In 2012,
Morris et al14 found no evidence of fetal oocyte mosaicism for triso‐
mies 16, 21 and 22. They analyzed eight karyotypically normal female
fetuses between 10 and 14 gestational weeks; they used FISH to find
the possibly trisomic cells in ovarian tissues without differentiating the
meiotic and pre‐meiotic cells with immune reactions, and used skin
samples from all fetuses for karyotyping and control. They found a
very low number of trisomic cells (0.025%), and the number of trisomic
cells found in ovary and skin samples was not significantly different.
What might be the reasons for the discordant results? Morris
15
et al used different sample processing, control tissue and FISH
analysis. However, more importantly, Morris et  al also examined
the fetal ovarian samples in the first and early second trimester,
just before the accumulation of trisomy 21 cells during the progres‐
sion of the fetal oogenesis, which is an essential part of the Oocyte
Mosaicism Selection model.
In this paper, we aimed to extend Hulten's oocyte mosaicism
hypothesis to T13. According to traditional dogmas, it has the same
pathomechanism as T21 (meiotic nondisjunction). To ensure the most
consistent conditions, we used immunohistology and FISH for chro‐
mosome 13 to determine the copy number in ovarian cells. We an‐
alyzed an average of 916 STAG3‐positive and 928 STAG3‐negative
cells in seven cases; the mean incidence of chromosome 13 trisomies
was 0.91% in STAG3‐negative and 2.04% in STAG3‐positive cells. The
average gestational age was 18.71 weeks. For the control population,
we used blood lymphocytes from two adults with normal karyotypes.
The results show that there was no significant difference in the
incidence of the STAG3‐negative trisomic cells in the two studies.
The results support our hypothesis that the oocyte mosaicism is the
main causative factor not only for T21 but also for other aneuploid‐
ies (for example T13).
We found a significant difference in the incidence of the STAG3‐
positive trisomic cells when compared with the results of Hultén
et al (2.04% in T13 cells vs 0.66% in T21 cells). The reason for this
might be the higher average gestational age (which can lead to more
cells entering into meiosis I.).
We also found that the number of T13 cells was significantly in‐
creased with gestational age.
It is appealing to conclude that oocyte mosaicism can play a
major role in the formation of the most common trisomies, instead
 |
6       BABAY et al.
of current dogma, which includes the assumption that the most com‐
mon trisomies are often caused by the separation failure of the ma‐
ternal and paternal chromosomal homologs.
Further methods can be helpful to examine this theory, eg, some
molecular genetic techniques, mostly the next generation sequenc‐
ing. Next generation sequencing has the advantage that it can provide
information on all 24 types of chromosomes. This diagnostic method
offers widescreen testing, avoiding diagnostic errors resulting from
chromosome mosaicism caused by malsegregation of chromosomes
or chromosome loss in the early mitotic divisions, which is relatively
common in cleavage stage embryos.16 With next generation sequenc‐
ing, it is possible to prove that.17 However, researchers have not as yet
investigated ovarian germ cells in pre‐meiotic mitosis. In principle, the
method can be extended to ovarian germ cells, but the technical dif‐
ficulties—for example, that the ovarian stem cells can only be isolated
from embryonic ovaries, as they develop during embryonic life—make
it challenging to implement the method correctly at present.
If we accept that, according to this theory, the trisomic oocytes
may be retarded in their maturation in comparison with normal oo‐
cytes, we have the possibility of reducing trisomic pregnancies with
the preservation of the ovarian oocyte reserve by reducing the
number of unnecessary ovulations. One method of oocyte reserve
F I G U R E 5   Demonstration of the
Oocyte Mosaicism Model. The right side
of the figure shows the regular meiosis.
The upper left corner of the picture shows
the primer nondisjunction that happens
before meiosis, at the time of the pre‐
meiotic mitotic steps. (During mitosis, a
lack of a chiasma can lead to segregation
at anaphase where a chromosome and
a chromatid will be in one daughter cell,
and one chromatid in the other. These
steps are not illustrated.) Instead of the
meiotic nondisjunction of a normal diploid
oogonium, the cause of the trisomy
is an obligate—so‐called secondary—
nondisjunction of a trisomic oogonium
that enters meiosis. (Red arrow shows the
pre‐meiotic mitotic step) [Colour figure
can be viewed at wileyonlinelibrary.com]
preservation is surprisingly obvious: the application of oral contra‐
ceptive pills reduces redundant ovulations.9,10,18
5 | CO N C LU S I O N
Though more research is likely to be needed to accept the Oocyte
Mosaicism Selection model, it seems to represent a change in dogma
when speaking of the background of trisomies. This study shows
that besides T21, the Oocyte Mosaicism Selection model could be
extended to T13 as well. The crucial factor for T13 seems to be the
pre‐meiotic/mitotic T13 mosaicism, leading to a so‐called secondary
meiotic nondisjunction of those oocytes with three chromosomes
13. While the model remains a controversial hypothesis, this type
of oocyte mosaicism might be a general characteristic and could ex‐
plain the function of the ovarian reserve.
AC K N OW L E D G M E N T S
The authors would like to thank Dr. Júlia Schönléber for her expert
help in sample preparation, and Linda Gyurcsó‐Deák for her profes‐
sional support in the FISH analysis.
BABAY et al.
C O N FL I C T O F I N T E R E S T
The authors have stated explicitly that there are no conflicts of inter‐
est in connection with this article.
ORCID
Lilla É. Babay  https://orcid.org/0000-0002-4850-0325
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How to cite this article: Babay LÉ, Horányi D, Győrffy B,
Nagy GR. Evidence for the Oocyte Mosaicism Selection
model on the origin of Patau syndrome (trisomy 13). Acta
Obstet Gynecol Scand. 2019;00:1–7. https​://doi.org/10.1111/
aogs.13694​