Open Journal of Pediatrics, 2011, 1, 79-86
doi:10.4236/ojped.2011.14019 Published Online December 2011 ( OJPed
Published Online December 2011 in SciRes.
Mechanism of origin in two cases of chimerism
Antonella Minelli1,2*, Andrea Guala3,4, Albert o Groppo1,2, Gabriella Restagno5, Roberto Lala6,
Silvia Einaudi6, Mariaelena Repici6, Emilio Merlini7, Luca Sbaiz5, Valentina Asnaghi 5,
Ana Graciela Lopez8, Paola Angellotti3, Silvia Cristina9, Cesare Danesino1,2
1Dipartimento di Medicina Molecolare, Sezione di Biologia Generale e Genetica Medica, Università degli Studi di Pavia, Pavia,
2Istituto di Ricerca e Cura a Carattere Scientifico IRCCS Policlinico San Matteo, Pavia, Italy;
3Struttura Complessa Pediatria, Ospedale Castelli, ASL VCO, Verbania, Italy;
4Master in Malattie Rare, Università degli Studi di Torino , Torino , Italy;
5Dipartimento di Diagnostica, Diagnosi e Consulenza Genetica, Ospedale Regina Margherita—S. Anna, Torino, Italy;
6Struttura Complessa Endocrinologia e Diabetologia, Ospedale Regina Margherita—S. Anna, Torino, Italy;
7Struttura Complessa Urologia, Ospedale Regina Margherita—S. Anna, Torino, Italy;
8Struttura Complessa Pediatria, Ospedale Civile, ASL NO, Borgomanero, Italy;
9Struttura Complessa Anatomia Patologica, Ospedale Civile, ASL NO, Borgomanero, Italy.
Email: *
Received 3 October 2011; revised 16 November 2011; accepted 21 November 2011.
Chimerism is defined as the presence in a subject of
more than one stable and genetically distinct cell line;
cases reported so far include both patients with am-
biguous genitalia and healthy subjects. The biological
mechanisms, which may give origin to chimeras, are
complex, and can be understood by analyzing DNA
samples of the patients and their parents using mo-
lecular techniques. The objective of this study is to
identify the mechanism of origin for the 2 cases we
report. The first patient is a phenotipically normal
girl with normal (external and internal) genitalia; the
second patient had ambiguous genitalia and under-
went surgery. DNA was purified from blood samples
and, limited to Patient 1, from a sample of biliary
cyst. Short tandem repeat polymorphisms were ana-
lyzed in order to identify the relative parental con-
tribution to the patients. Molecular analyses carried
out on the first patient are not fully informative be-
cause of two possible explanations (i.e. parthenoge-
netic and andrognetic chimera), while in the second
case the presence of four alleles at some markers al-
lowed us to identify a tetragametic chimera origin-
nated from the fusion of two distinct embryos. Stud-
ies carried on one single tissue may not always be
conclusive as they do not allow the precise identifica-
tion of the mechanism of origin. In these cases, stud-
ies on more tissues are strongly suggested.
Keywords: Chimerism; Androgenetic Chimera; Parthe-
nogenetic Chimera; Tetragametic Chimera; Microsatel-
lite Polymorphism Analysis
Chimerism is defined as the presence of more than one
stable and genetically distinct cell line [1] originated
independently from one another [2]. Thus chimerism is
different from mosaicism, in which the cell lines have a
common, single cell progenitor.
This condition is rare in humans: Malan et al. in 2006
counted about 30 cases [3] and this number increased a
little in these last years.
When both female (46,XX) and male (46,XY) cell
lines are present, the phenotype, ranging from normal
male to normal female through various degree of am-
biguous genitalia, is related to their distribution in the
gonads. The ratio between the two cell lines in different
tissues does not allow a precise prediction of the status
of gonads or the phenotyp e of external genitalia [3].
The origin of the cell lines can be defined at a mo-
lecular level using a number of polymorphic markers
and comparing the genetic profile of the patient with
those of the parents. Only few cases, especially in these
past years, have been studied this way, allowing to pro-
pose at least four different mechanisms of origin, namely
tetragametic chimerism, parthenogenetic chimerism,
chimera resulting from the fertilization of the second
polar body and androgenetic chimerism. These mecha-
nisms were reviewed by Malan in 2006 [3]; details are
provided in the Discussion section of this paper.
We report two cases of chimerism in which molecular
analysis allowed us to suggest either parthenogenetic or
A. Minelli et al. / Open Journal of Pediatrics 1 (2011) 79-86
androgenetic origin in the first case and to identify a
tetragametic mechanism of origin in the second.
2.1. Patient 1
Patient 1 was born at 37 weeks’ gestation after an un-
eventful pregnancy, to healthy, unrelated Caucasian par-
ents. Birth weight was 2600 g, length was 45 cm, and
head circumference was 43 cm. Parental karyotype is
Chorionic villus sampling was performed upon pa-
rental request, and th e results showed two cell lines. One
cell line with a 46,XX karyotype was seen in short term
cultures, while a 46,XY cell line was observed in long
term cultures. Control amniocentesis showed 46,XX in
21 clones from 3 independent cultures and 46,XY from 4
colonies from a single culture. Ultrasound examination
consistently revealed a fetus with no malformations and
with normal female external genitalia.
At birth, physical examination revealed a fully normal
child with no malformations or dysmorphic features, and
normal female external genitalia; abdominal ultrasound
examination in the first week of life demonstrated the
presence of normal uterus and ovaries.
The placenta showed morphological alterations sug-
gestive of “chimerism”: it weighed 1730 g, and upon
sectioning, a marginal area of vesicle formation consis-
tent with molar changes was observed. At microscopic
examination, the placental parenchyma showed mainly
third trimester chorionic villi with widespread small ar-
tery lesions in both secondary and tertiary stem villi.
There were marked villous hydrops with central cistern
formation consistent with complete hydatidiform mole.
The mixed population of morphologically normal cho-
rionic villi and villi with the typical chan ges of complete
hydatidiform mole was highly suggestive of placental/
fetal mosaicism [4,5]. These data, in addition to the re-
sults observed antenatally, were an indication to perform
cytogenetic analysis of the newborn, which showed a
46,XX[31]/46,XY[19] karyotype. A similar ratio of the
two cell lines was observed during follow up.
Normal development was recorded during follow up.
At the age of 2, a slightly enlarged liver was found, and
an ultrasound examination demonstrated a cystic forma-
tion of 7 cm which was diagnosed as a “congenital bi-
liary cyst”, which was surgically removed.
2.2. Patient 2
Patient 2, Caucasian, was admitted to the hospital be-
cause of a sex determination disorder. Male sex was at-
tributed at birth, but external genitalia, ambiguous and
classified as Prader type III, were represented by the
presence of a penoclitoris, perineal hypospadia, uro-
genital sinus, bifid scro tum and bilateral cryptorchidism.
At birth, chromosomal analysis on peripheral blood
lymphocytes revealed two cell lines, 46,XX[49]/46,XY
[15]. A second karyotype analysis few months later con-
firmed the presence of the two cell lines: 46,XX[67]/
46,XY[33], while cultured fibroblasts from a skin biopsy
showed only 46,XX[16]. Both parents showed normal
karyotype. These results led to a diagnosis of 46,XX/
46,XY chimer ism.
QF-PCR analysis with chromosome specific probes
(13, 18, 21, X and Y) revealed the presence of DNA be-
longing to two different cell lines, one female and one
male. The X-chromosome signal proved to be stronger
than the Y-chromosome signal.
Endocrine evaluation showed LH: 4.08 mU/ml; es-
tradiol: 8 pg/ml; testosterone: 1.08 ng/ml; all these val-
ues as well as 17OHP, androstenedione and DHEAS
were within normal range. FSH (9.45 mU/ml) was out o f
range, and it was similar to what is observ ed in females.
Transabdominal ultrasound showed a uterus behind
the bladder and two gonadal structures, while contrast
X-rays demonstrated a straight female-type urethra, va-
gina and uterus. Contrast medium reached the tubae bi-
Laparoscopy revealed on the left side an uterus as
well as a female gonad and tuba, with internal inguinal
ring. On the right side, the internal inguinal ring was
open and a testicular structure was present in the abdo-
Detection of a morphologically normal uterus, to-
gether with a tuba and a female gonad led to decide to
change the anatomical sex of the baby from male to fe-
male. This decision was discussed with the baby’s par-
ents and psychological support was provided. The baby
underwent female genitoplasty with clitoral reduction.
The right gonad was removed together with a cystic
formation associated to it.
Histopathology of the gonadal tissue revealed the
presence of ovarian parenchyma and testicular tissue, in
particular seminiferous tubules with interstitial fibrosis
and Leydig cells. Structures similar to rete testis, epidi-
dymis and vascular plexus were also detected. The find-
ing was compatible with a diagnosis of ovotestis. The
cystic structure was characterised by osteocartilaginous,
thyroideal and mature connective tissue areas. Karyo-
typing was performed on a sample of the cystic tissue
and resulted 46,XX. Histological diagnosis was of a
mature cystic teratoma.
Biopsy was not performed on the left gonad because it
presented with a macroscopically normal aspect, and in
order to preserve the supposed ovarian tissue.
opyright © 2011 SciRes. OJPed
A. Minelli et al. / Open Journal of Pediatrics 1 (2011) 79-86 81
3.1. DNA Purification
After informed consent, blood samples from the two
patients and their parents were obtained. Limited to Pa-
tient 1, DNA was also purified from a fragment of bil-
iary cyst surgically removed. DNA was purified by rou-
tine methods using GenElute™ Blood Genomic DNA
Kit (Sigma-Aldrich®).
3.2. STRPs Analysis
The short tandem repeat polymorphisms (STRPs) to be
analysed were chosen on several different chromosomes,
on the basis of their heterozygosity (see Table 1 and
Ta bl e 2 for a complete list of markers for patient 1 and
patient 2 respectively).
Genotyping of STRPs was performed using ABI
PRISM™ multicolor fluorescent dye technology, based
on labeling DNA fragments with different color fluores-
cent dyes by PCR amplification. PCR conditions were
developed in our lab. The PCR products are displayed as
electropherograms showing fluorescence intensity as a
function of fragment size or migration time. Peak Scan-
ner SoftwareTM v1.0 by Applied Biosystems provides
peak detection (areas and heights) relative to alleles am-
plified as DNA fragments.
When parents shared an allele of the same size, we
calculated the ratio between peak heights and compared
it with the ratio of cell lines as demonstrated by cytoge-
netic analysis. This method allowed to assess the origin
of that allele (maternal, paternal or both of them) and
infer a single or double, maternal and/or paternal contri-
We analyzed several STRPs localized on different auto-
somes, in addition to the X chromosome (see Table 1
and Table 2 for a complete list of markers for patient 1
and patient 2 respectively).
Informative and partially informative markers have
been found. We defined a marker as informative when it
allowed us to prove a double paternal and/or maternal
contribution. A marker was considered partially infor-
mative when it showed three alleles and the origin of the
extra allele could not be inferred because its origin could
be maternal and/or paternal.
Table 1 and Ta ble 3 show results for patient 1; Table
2 and Table 4 illustrate findings for patient 2. Figure 1
shows examples of informative markers for both patient
1 and 2.
4.1. Patient 1
Eight autosomal markers are informative, since they
Table 1. List of the STRPs studied for patient 1, showing size
(in bp) and which alleles were observed in the patient and in
her parents. Informative STRPs are shown in bold print (I:
informative marker; N/I: not informative marker).
STRP Father Mother Patient Notes
D1S1609 178/194174/182 178/182/194 Id
D1S3723 182 190/194 182/190 N/I
D2S1361 170/186 165/186 N/Ia
D2S2739 291/317 291/301 N/Ia
D3S4555 205/213205/209 205/213 N/Ia
D3S2406 330/346326 326/330/346 I
D4S3355 136 136/144 136/144 N/Ia
D4S2426 260 248/264 248/260 N/I
D5S1470 170/186 166/186 N/Ia
D5S815 286/290 286/294 N/Ia
D7S1808 255/273258/261 255/258/273 Id
D7S1805 198/216198/216 216 N/I
D7S1820 251/255263 251/255/263 I
D7S796 176/184180/188 176/180/184
D7S1830 221 221/225 221/225 N/Ia
D8S1130 133/137137/146 133/137/146 Ic
D8S586 244/252240/248 244/248 N/Id
D10S189 185 183/185 183/185 N/Ia
D10S1779 266/268264/268 264/266/268 Ic
D10S547 237/239239/247 239/247 N/Ia
D10S570 285/295291/295 291/295 N/Ia
D12S390 139/154148 139/148 N/I
D12S1586 157/169165/167 157/165 N/I
15DUP10 398 395 395/398 N/I
15DUP12 238 234 234/238 N/I
D15S822 284 /288260/264 260/284/288 I
D15S643 195/213217 195/213/217 I
COMPLEX 264/268264/268 264/268 N/I
EVI20 191/193191 191/193 Ib
D20S604 137/141137/141 137 N/I
D20S1151 251/279243/247 243/279 N/Id
DXS9908 222 224/230 222/224 I
GATA172D05 106 114/126 106/126 Id
aThe two alleles show peaks of similar size; bSTRP demonstrating double
paternal contribution; cOnly partially informative marker; dData consistent
with those found analyzing the biliary cyst.
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A. Minelli et al. / Open Journal of Pediatrics 1 (2011) 79-86
Table 2. List of the STRPs studied for patient 2, showing size
(in bp) and which alleles were observed in the patient and in
her parents. Informative STRPs are shown in bold print. (I:
informative marker; N/I: not informative marker).
STRP Father MotherPatient Notes
D1S3723 186/190 145/186 145/186 Ib
D1S1609 190/202 178/186 178/186/190 I
D2S1361 175/183 179/183 175/179/183 Ic
D3S2406 330 326/342 326/330/342 I
D5S1470 182/190 186/194 182/186/190/194I
D5S815 256/290 286/290 256/286/290 Ic
D7S1805 213/217 198/221 198/213/217/221I
D7S796 188 176/191 176/188/191 I
D8S1130 132/150 132/141 132 N/I
D10S1779 265 274/276 265/274/276 I
D10S570 288 294 288/294 N/I
D12S390 148/157 152/157 148/152/157 Ic
D15S643 209/213 209 209/213 N/Ia
D20S1151 246/274 246/250 246/250/274 Ic
DXS9908 224 228 224/228 I
GATA172D05 130 114/122114/122/130 I
aThe two alleles show peaks of similar size; bSTRP demonstrating
double maternal contribution; cOnly partially informative marker.
Table 3. Peak heights (in relative fluorescent units) and their
ratios for STRPs showing two different alleles, and the parents
sharing one of them for patient 1.
Allele 1 Allele 2
STRP Size (b p) Height Size (bp) Height Ratio
D2S1361 165 8876 186 8578 1.03
D2S2793 291 6720 301 6437 1.04
D3S4555 205 6418 213 3632 1.76
D4S3355 136 3049 144 2810 1.09
D5S1470 166 2555 186 2658 1.04
D5S815 286 4461 294 4166 1.07
D7S1830 221 268 225 241 1.11
D10S189 183 570 185 703 1.23
D10S547 239 215 247 185 1.16
D10S570 291 977 295 630 1.55
EVI20 191 1794 193 661 2.71
Tabl e 4. Peak heights (in relative fluorescent units) and their
ratios for STRPs showing two different alleles, and parents
sharing one of them for patient 2.
Allele 1 Allele 2
STRP Size (bp)Height Size (bp) HeightRatio
D1S3723145 767 186 1494 1.95
D15S643209 157 213 134 1.17
show double paternal and single maternal contribution.
As regards EVI20, it has been considered an informative
marker because the ratio between peak heights is con-
sistent with the ratio of cytogenetic analysis (see Table
3). Markers D8S1130 and D10S1779 reveal three alleles
and are reckoned partially informative, because the ori-
gin of the extra allele cannot be assessed.
X-linked markers are informative, since they show
double paternal (considering the Y chromosome) and
single maternal contribution.
The same results were observed when analyzing DNA
extracted from biliary cyst, tested only for D1S1609,
D7S1808, D7S796, D8S586, D20S1151 and GATA
172D05 markers.
The 10 informative markers clearly reveal double pa-
ternal contribution, while, up to now, double maternal
contribution has never been proven.
4.2. Patient 2
Two informative mark ers (D5S1470 and D7S1 805) on 2
chromosomes show 4 different alleles, proving a double
maternal and double paternal contribution.
In addition, other 5 autosomal markers are also infor-
mative, since they show double maternal and single pa-
ternal contribution. Though marker D1S3723 shows
only two alleles, it has been considered an informative
marker, because the ratio between peak heights is con-
sistent with the ratio of cytogenetic analysis (see Table
Four markers are partially informative, since they
show three different alleles and the origin of the extra
allele cannot be assessed.
Both X-linked markers are informative because they
show double paternal contribution (considering the Y
Moreover, marker GATA172D05 shows double ma-
ternal contribution.
On the whole, these data are consistent with double
paternal and double maternal contribu tions for this case.
Since chimerism is characterized by the independent
origins of the two cell lines, three or four alleles at a
opyright © 2011 SciRes. OJPed
A. Minelli et al. / Open Journal of Pediatrics 1 (2011) 79-86
Copyright © 2011 SciRes.
Figure 1. Examples of informative markers for patient 1 (on the left) and patient 2 (on the right). Mothers’ electropherograms in the
higher row, fathers’ in the lower and patients’ in the middle.
specific locus or skewed dosage of two alleles can be
observed [2]. The interpretation of results, even in con-
junction with clinical data, may be difficult in some
cases, since they may not allow the identification of the
precise mechanism of origin. The mechanisms of origins
are summoned in Table 5 and are now discussed in some
5.1. Tetragametic Chimerism
The fusion of two different and independently fertilized
zygotes leads to the tetragametic chimera. This mecha-
nism is the most frequent and, to date, it has been dem-
onstrated in 9 patients reported [2,6-13]. In this case, 4
different alleles (2 maternal and 2 paternal) can be ob-
served at some loci in the patient.
5.2. Parthenogenetic Chimerism
The parthenogenetic chimera generally arises from an
oocyte undergoing parthenogenetic activation, giving
rise to two identical daughter cells which are then ferti-
lized by two different spermatozoa. This mechanism
(“Parthenogenetic/1” in Table 5), described by Giltay,
has been demonstrated only once [14]. In this case, 3
alleles (2 paternal and 1 maternal) can be observed at
some loci in the patient.
However, this is not the only mechanism which can
result in such a chimera. In fact, a similar but slightly
different mechanism was proposed and demonstrated by
Strain and colleagues in 1995 (“Parthenogenetic/2” in
Table 5) [15]. The authors proposed a parthenogenetic
activation of the oocyte, producing 2 identical maternal
cells. One of these cells was then fertilized by a Y-bear-
ing sperm, while the other underwent diploidization,
producing a parthenogenetic cell line. In this case, the
parthenogenetic cell line must show only one maternal
allele, whereas the other cell line may show two alleles
(1 paternal and 1 maternal) at some loci in the patient.
When analyzing a tissue made up of these two cell lines,
2 alleles can be observed at some loci in the patient,
since the two cell lines share the same maternal alleles.
5.3. Chimera Resulting from the Fertilization of
the Second Polar Body
Though often considered, the fertilization of the second
polar body has never been proved at a molecular level.
This mechanism requires a normal fertilization followed
by the extrusion of the second polar body and its fertili-
zation by a second spermatozoon. In this case, some
distal markers may show 4 alleles (2 paternal and 2 ma-
ternal), while centromeric markers may show 3 alleles (2
paternal and 1 maternal) at some loci in the patient.
These differences are due to crossing-over events occur-
ring during meiosis. Since second polar body fertiliza-
tion and parthenogenetic chimera may show similar mo-
lecular results, neither mechanism can be ruled out with
certainty in the cases repoted by Chen, Draper, and r
A. Minelli et al. / Open Journal of Pediatrics 1 (2011) 79-86
Table 5. Mechanisms of origin of chimeras, possible results of STRP analysis and related references. In case of parthenogenetic and
androgenetic chimerism, different authors suggested different mechanisms resulting in such chimeras.
Mechanism of origin Paternal
contribution Maternal
contribution Max number of alleles that may be
observed in the patient References
Tetragametic 2 2 4 2, 6 - 13
Parthenogenetic/1 2 1 3 14
Parthenogenetic/2 1 1 2 15
Fertilization of the second polar body2 2/3a 3/4a 16 - 18
Androgenetic/1 1 1 2 19 - 20
Androgenetic/2 2 1 3 21
Androgenetic/3 2 1 3 22
Androgenetic/4 2 1 3 22
aDue to crossing-over events during meiosis, centromeric markers may show 3 maternal alleles, whereas distal markers may show only 2, thus altering the
maximum number of alleles in a tissu e made up o f 2 cell lines.
Mosebach [16-18] .
5.4. Androgenetic Chimera
After a normal event of fertilization of an oocyte and a X
spermatozoon, endoreplication of the paternal pronu-
cleous takes place; the following cell cleavage leads to a
diploid (with maternal and paternal pronuclei) and a
haploid (with only a paternal pronucleus) cells. A second
event of endoreplication of the paternal genome in the
haploid cell brings to the androgenetic cell line. This
mechanism has been demonstrated twice [19,20]. In this
case, the androgenetic cell line must show only one pa-
ternal allele, whereas the other cell line may show two
different alleles (1 paternal and 1 maternal) at some loci
in the patient. When analyzing a tissue made up of these
two cell lines, 2 alleles can be observed at some loci in
the patient, since the two cell lin es share the same pater-
nal alleles (“Androgene tic/1” in Table 5).
A related mechanism was proposed by Surti in 2005
[21]: it requires the fusion of a normal zygote (fertilized
by a Y-carrying spermatozoon) and an empty oocyte
fertilized by a X-carrying spermatozoon and undergone
to endomitosis. This second mechanism has been dem-
onstrated only once. In this case, the androgenetic cell
line must show only one paternal allele, while the other
cell line may show two different alleles (1 paternal and 1
maternal) at some loci in the patient. When analyzing a
tissue made up of these two cell lines, 3 alleles can be
found at some loci in the patient, since the two cell line
originated from two different spermatozoa (“Androge-
netic/2” in Table 5). We would like to point out that
Surti described the placenta as cystic when reporting the
clinical history, and that chimerism was confined to the
placenta [21].
Furthermore, other 2 mechanisms, each involving a
tri-pronuclear (3PN) zygote, were proposed by Robinson
in 2007 [22]. The authors suggested that, after the fer-
tilization of an oocyte with two normal spermatozoa
(leading to a 3PN zygote), fully diploid two-celled em-
bryos can occur when only one of the three haploid ge-
nomes replicates and segregates at the end of the one-
cell stage. In this case, the androgenetic cell line may
show 2 alleles (both paternal) at some loci in the patient,
whereas the other cell line may show 2 alleles (1 pater-
nal and 1 maternal) at some loci. When analyzing a tis-
sue made up of these two cell lines, 3 alleles may be
found at some loci in the patient, because 2 spermatozoa
are involved (“Androgenetic/3” in Table 5).
Alternatively, such embryos can also arise when a
3PN zygote undergoes cell division without genome
replication, leading to a diploid and a haploid cell, and
consequent replication of the haploid genome. In this
case, the androgenetic cell line must show only one pa-
ternal allele, while the other cell line may show two dif-
ferent alleles (1 paternal and 1 maternal) at some loci in
the patient. When analyzing a tissue made up of these
two cell lines, 3 alleles can be found at some loci in the
patient, because 2 spermatozoa are involved (“Androge-
netic/4” in Table 5).
It is worth noting that in cases of androgenetic chi-
merism, complete hydatidiform moles, placental mes-
enchimal dysplasia, cystic placenta, hemangiomas and
liver cysts are often found during pregnancy [22].
5.5. Patient 1
Results showed 3 alleles at some loci, two of them have
a paternal origin, while the remaining is maternal. Hence
they are consistent with both parthenogenetic and an-
drogenetic hypothesis. Considering both molecular ana-
lysis and the clinical description of the placenta, we con-
sidered the androgenetic hypo thesis very likely. We then
studied other tissues in order to identify an androgenetic
opyright © 2011 SciRes. OJPed
A. Minelli et al. / Open Journal of Pediatrics 1 (2011) 79-86 85
cell line alone which could support this hypothesis, but
we were not able to find it. Based on these data, we
cannot rule out either mechanism.
5.6. Patient 2
Results are consistent only with tetragametic chimerism,
since it is the only hypothesis which can explain the 4
alleles we found.
A routine chromosome analysis on a single tissue may
not identify all cases of chimerism (in fact, in case 2
fibroblasts only show a 46,XX karyotype). In addition,
even when two cell lines are observed in one single tis-
sue, the interpretation of resu lts may not lead to the clear
identification of the mechanism which gave rise to the
chimera. It is therefore strongly sugg ested to study more
than one tissue in patients with ambiguous genitalia, in
order to rule out the possibility of chimerism or mosaic-
ism and to identify clearly the mechanism of origin.
In every case of ambiguous genitalia, sistematic sur-
velliance is certanly needed to check the oncologic risk
of the dysgenetic gonad. It is currently still a matter of
debate whether ultrasound examination alone can be
used as a reliable method for diagnosing the presence of
structural abnormalities in the gonads, or biopsy should
be performed in all cases. Biochemical markers of neo-
plasia ought to be, of course, included in follow up
Specific counseling issues arise when chimerism is
diagnosed prenatally [12]. In fact it is not possible to
predict what the phenotype will be at term, since it may
range from completely normal to the presence of am-
biguous genitalia.
Chimerism is an interesting biological problem, in
which the genotype-phenotype correlation is still far
from being defined. Moreover, given that chimeras can
be phenotypically normal male or female, and since the
number of cases studied is, up to now, limited, it is rea-
sonable to assume that chimeras are under-diagnosed
and less rare than previously believed. Accurate clinical
examination and extended genetic investigations will
provide new insights into the biological questions still
Dr. Andrea Guala achieved a Master in Rare Diseases at Università
degli Stud i di Torino, Italy.
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