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A high level of tetrasomy 9p mosaicism but no clinical manifestations other than moderate oligozoospermia with chromosomally balanced sperm: a case report

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Hela Bellil
Hela Bellil
Hela Bellil
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Bérénice Hervé
Bérénice Hervé
Elodie Herzog
Elodie Herzog
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Jean-Marc Ayoubi
Jean-Marc Ayoubi
Jean-Marc Ayoubi
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Tetrasomy 9p (ORPHA: 3310) (i(9p)) is a rare chromosomal imbalance. It is characterized by the presence of a supernumerary chromosome incorporating two copies of the short arm of chromosome 9 and is usually present in a mosaic state postnatally. Depending on the level of mosaicism, the phenotype ranges from mild developmental delay to multiple congenital anomalies with severe intellectual disability. Here, we report on a patient diagnosed with i(9p) mosaicism after the recurrent failure of in vitro fertilization. Although the patient’s clinical phenotype was normal, the level of mosaicism varied greatly from one tissue to another. A sperm analysis evidenced subnormal spermatogenesis with chromosomally balanced spermatozoa and no risk of transmission to the offspring. Although individuals with i(9p) and no clinical manifestations have rarely been described, the prenatal diagnosis of this abnormality in the absence of ultrasound findings raises a number of questions.
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GENETICS
A high level of tetrasomy 9p mosaicism but no clinical manifestations
other than moderate oligozoospermia with chromosomally balanced
sperm: a case report
Hela Bellil
1,2
&Bérenice Herve
1,2
&Elodie Herzog
3
&Jean-Marc Ayoubi
1,3
&François Vialard
1,2
&Marine Poulain
1,3
Received: 16 October 2019 /Accepted: 4 January 2020 /P ublished online: 24 January 2020
#Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
Tetrasomy 9p (ORPHA: 3310) (i(9p)) is a rare chromosomal imbalance. It is characterized by the presence of a supernumerary
chromosome incorporating two copies of the short arm of chromosome 9 and is usually present in a mosaic state postnatally.
Depending on the level of mosaicism, the phenotype ranges from mild developmental delay to multiple congenital anomalies
with severe intellectual disability. Here, we report on a patient diagnosed with i(9p) mosaicism after the recurrent failure of
in vitro fertilization. Although the patient’s clinical phenotype was normal, the level of mosaicism varied greatly from one tissue
to another. A sperm analysis evidenced subnormal spermatogenesis with chromosomally balanced spermatozoa and no risk of
transmission to the offspring. Although individuals with i(9p) and no clinical manifestations have rarely been described, the
prenatal diagnosis of this abnormality in the absence of ultrasound findings raises a number of questions.
Keywords Mosaicism .Sperm FISH .Te trasomy 9p .Spermatogenesis .Meiotic arrest
Introduction
Tetrasomy 9p is a rare chromosome imbalance that was first
described by Ghymers et al. in 1973 [1]. It is defined by the
presence of an isochromosome for the short arm of chromo-
some 9 (i(9p)) in a homogenous or mosaic state. Tetrasomy 9p
is frequently caused by nondisjunction during meiosis II and
then duplication of the short arm and loss of the long arm [2].
Short arm isochromosomes have also been reported for chro-
mosomes 5, 8, 10, 12, 18, and 20, and all of these conditions
are associated with a severe phenotype.
Tetrasomy 9p is a rare event, although there are a few
literature reports of prenatally and postnatally diagnosed mo-
saic and non-mosaic cases [3]. The clinical manifestations
associated with i(9p) are highly variable and include intellec-
tual deficiency and developmental delay (in 73% of cases),
growth delay (39%), intra-uterine growth retardation (28%),
skeletal anomalies (55%), genital/urinary tract anomalies
(43%), and ophthalmologic anomalies (42%). Microcephaly
is present in 20% of cases, and dysmorphic features include
abnormal ears (69%), hypertelorism (46%), micro-
retrognathia (45%), and cleft lip/palate (32%) [3]. It has been
suggested that the severity of handicap is related to the degree
of mosaicism [4–6]. Only a few patients with a normal phe-
notype have been described. Here, we report a patient with
tetrasomy 9p mosaicism but no clinical manifestations other
than moderate oligozoospermia with chromosomally bal-
anced sperm. We compared our clinical, cytogenetic, and mo-
lecular findings with previous reports on patients with a nor-
mal phenotype.
Clinical report
A 41-year-old man and his 37-year-old wife were referred for
cytogenetic assessment after the failure of four in vitro fertil-
ization (IVF) attempts and eight embryo transfers. The indi-
cation for IVF was moderate oligoasthenozoospermia. The
*François Vialard
francois.vialard@uvsq.fr
1
Université Paris-Saclay, INRAE, ENVA, UVSQ, BREED,
78350 Jouy-en-Josas, France
2
Genetics Federation, CHI de Poissy St Germain en Laye,
F-78303 Poissy, France
3
Department of Gyneacology, Obstetrics and Reproductive Medicine,
Hopital Foch, F-92150 Suresnes, France
Journal of Assisted Reproduction and Genetics (2020) 37:573–577
https://doi.org/10.1007/s10815-020-01690-0
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Tetrasomy 9p is often associated with multiple malformations. Nevertheless, few cases of mosaic tetrasomy 9p without clinical symptoms have been reported (Sait & Wetzler, 2003, Bellil et al., 2020McAuliffe et al., 2005;Shu et al., 2021). Here, we describe an extraordinary case of mosaic tetrasomy 9p without clinical symptoms from conception until 2.5 years of age. ...
... To the best of our knowledge, this is the ninth case of mosaic tetrasomy 9p with no clinical symptoms to be reported in the literature, and the first case in which the phenotype was documented from early pregnancy through the postnatal period. The mosaic levels for the eight cases that have been previously described (Table 2) ranged from 6% to non-mosaic tetrasomy 9p (Baronchelli et al., 2011;Bellil et al., 2020;McAuliffe et al., 2005;Ogino et al., 2007;Papoulidis et al., 2012;Sait & Wetzler, 2003;Shu et al., 2021). The mosaic ratio of our case was within this range by 21.5%. ...
... This difference may be attributable to poor genetic stability and the loss of trisomic cells during long-term culture of amniotic fluid cells, which contrasts with the case of monomeric cells. We reviewed the mosaic levels of 9p duplication detected by various testing methods that have been previously published (Table 3) (Bellil et al., 2020;Chen et al., 2014;Pinto et al., 2018). According to our findings, mosaic levels of 9p duplication decreased during prolonged culture, which may explain one previous observation of possible false-negative diagnoses of mosaic 9p duplication when testing cultured amniocytes (Chen et al., 2014). ...
Application of various genetic analysis techniques for detecting two rare cases of 9p duplication mosaicism during prenatal diagnosis
Article
Full-text available
  • Jun 2023
Background: The identification of genetic mosaicism and the genetic counseling needed following its discovery have been challenging problems in the field of prenatal diagnosis. Herein, we describe the clinical phenotypes and various prenatal diagnostic processes used for two rare cases of 9p duplication mosaicism and review the prior literature in the field to evaluate the merits of different methods for diagnosing mosaic 9p duplication. Methods: We recorded ultrasound examinations, reported the screening and diagnosis pathways, and analyzed the mosaic levels of the two cases of 9p duplication using karyotype analysis, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization analysis (FISH). Results: Case 1 had a normal clinical phenotype for tetrasomy 9p mosaicism, and Case 2 showed multiple malformations caused by both trisomy 9 and trisomy 9p mosaicism. Both cases were initially suspected after non-invasive prenatal screening (NIPT) based on cell-free DNA. The mosaic ratio of 9p duplication found via karyotyping was lower than what was discovered by CMA and FISH, in both cases. Contrary to previous findings, the mosaic level of trisomy 9 found by karyotype analysis was greater than what was found by CMA, in terms of complex mosaicism involving trisomy 9 and trisomy 9p, in Case 2. Conclusion: NIPT can indicate 9p duplication mosaicism during prenatal screening. Different strengths and limitations existed in terms of diagnosing mosaic 9p duplication by karyotype analysis, CMA, and FISH. The combined use of various methods may be capable of more accurately determining break-points and mosaic levels of 9p duplication during prenatal diagnosis.
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... Genome-wide cffDNA screening was initially performed at 11 weeks ga (fetal fraction: 7.0%) and showed multiple reductions in DNA from chromosomes 1, 2, 3, 4, 5, 6,7,8,11,12,13,14,18,20, and 21, as well as elevated amounts of DNA from the p-arm of chromosome 9 with a mean count-based z-score of 149.8 and aberrant region (9p24.3-9p13.1) z-score of 360.84, respectively. ...
... In the worst case scenario with mosaic state, one could have neurodevelopmental delay with metabolic disorder [11]. Individuals having no or mild features are rarely encountered [6][7][8][12][13][14], and here we present the eighth literature report on a patient with mosaic tetrasomy 9p exhibiting mild phenotype and normal intelligence. To our knowledge, she is also the first maternal case with the unique dicentric variety that was discovered by cell free fetal DNA prenatal screening test. ...
... This discovery has opened a new field for molecular diagnosis of cancer [26]. For our patient, persistent aberrant findings of reduction in DNA from chromosomes 1, 2, 3, 4, 5, 6,7,8,11,12,13,14,18,20, and 21 lead to concerns of malignancy. However, a consensus has not been reached on how to screen for malignancy in such cases. ...
First Case Report of Maternal Mosaic Tetrasomy 9p Incidentally Detected on Non-Invasive Prenatal Testing
Article
Full-text available
  • Mar 2021
Tetrasomy 9p (ORPHA:3390) is a rare syndrome, hallmarked by growth retardation; psychomotor delay; mild to moderate intellectual disability; and a spectrum of skeletal, cardiac, renal and urogenital defects. Here we present a Chinese female with good past health who conceived her pregnancy naturally. Non-invasive prenatal testing (NIPT) showed multiple chromosomal aberrations were consistently detected in two sampling times, which included elevation in DNA from chromosome 9p. Amniocentesis was performed and sent for chromosomal microarray, which was normal. Maternal karyotype revealed that mos 47,XX,+dic(9;9)(q21.1;q21.1)(24)/46,XX(9) presents mosaic tetrasomy for the short arm of chromosome 9p and is related to the NIPT results showing elevation in DNA from chromosome 9p. The pregnancy was uneventful, and the patient was delivered at term. Maternal samples were obtained at two different time points after delivery showed the same multiple chromosomal aberrations detected during pregnancy. This is a first report on an unusual case of mosaic isodicentric tetrasomy 9p in a healthy adult with normal intellect. With widespread adoption of NIPT for screening fetal aneuploidy and genome-wide copy number changes, a rise in incidental detection of maternal rare genetic syndrome will bring challenges in our current approach to genetic counselling and prenatal diagnosis.
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... Tetrasomy 9p (T9p), which was first defined in 1973(Ghymers et al., 1973, is a rare abnormality typically resulting from a supernumerary isochromosome and mostly documented after birth. The phenotype of T9p varies from fetuses with multiple abnormalities to phenotypically normal adults (Bellil et al., 2020;Shu et al., 2021). Fetuses with T9p usually exhibit abnormal ultrasound findings including facial clefts, fetal growth retardation (FGR), and Dandy-Walker variant . ...
... A case with full tetrasomy 9p in the blood, 65% mosaic in the buccal mucosa, was a health woman who was accidentally identified due to her previous pregnancy with an inv (7) baby (Papoulidis et al., 2012). Among the 8 cases reported with a clinically normal phenotype, the tetrasomic clone ranged from 6% to 100% in peripheral blood lymphocytes, except in five cases that had fertility related issues (5/8) (Papoulidis et al., 2012;Bellil et al., 2020;Shu et al., 2021). ...
Case Report: Prenatal diagnosis of fetal tetrasomy 9p initially identified by non-invasive prenatal testing
Article
Full-text available
  • Oct 2022
Tetrasomy 9p is a rare syndrome characterized by fetal growth restriction, Dandy-Walker malformation, cardiac anomalies, and facial abnormalities and is discovered by ultrasound during the prenatal examination. Herein, we report a fetus of tetrasomy 9p without obvious phenotypic manifestations during the first trimester that was identified by non-invasive prenatal testing (NIPT). NIPT revealed that the gain of 9p24.3–9p11 that was approximately 46.36 Mb in size. Karyotyping of amniocytes indicated an additional marker in all metaphase. Chromosome microarray and fluorescence in situ hybridization on uncultured amniocytes revealed tetrasomic of 9p24.3q13, and that the supernumerary chromosome is a dicentric isochromosome consisted of two copies of the 9p arm. Taken together, it was indicated that the fetal karyotype was 47,XY,+idic (9) (q13), and that multiple techniques are crucial to the prenatal diagnosis.
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... All CMs related to autosomal chromosomes were classified into the group of autosomal abnormalities, whereas CMs related to sex chromosomes were classified into the group of sex chromosomal abnormalities. With respect to the CM fraction, we defined a fraction greater than or equal to 50% as high and others as low (Bellil et al., 2020;Capalbo et al., 2021). As the results of karyotyping which were counted manually may introduce human error, the classification of the CM fraction was performed based on the results of CMA. ...
Prenatal Diagnosis of Chromosomal Mosaicism in Over 18,000 Pregnancies: A Five-Year Single-Tertiary-Center Retrospective Analysis
Article
Full-text available
  • May 2022
Background: Chromosomal mosaicism (CM) is a common biological phenomenon observed in humans. It is one of the main challenges in prenatal diagnosis due to uncertain outcomes, especially when fetal ultrasonographic features appear normal. This study aimed to assess the phenotypic features of CM detected during prenatal diagnosis and the risk factors affecting parents’ pregnancy decisions. Materials and methods: A retrospective cohort study involving 18,374 consecutive pregnancies that underwent prenatal diagnosis by karyotyping, fluorescence in situ hybridization (FISH), or chromosome microarray analysis (CMA) was conducted. The association of risk factors with malformations detected by ultrasound and pregnancy outcomes was assessed using the chi-square test and binary logistic regression. Discordant results between the different methods were identified and further analyzed. Results: During this five-year period, 118 (0.6%) patients were diagnosed with CM. The incidences of CM in the chorionic villus, amniotic fluid, and umbilical cord blood were 3.2, 0.5, and 0.7%, respectively. The frequency of ultrasound malformations in individuals with a high fraction of autosomal CM was significantly higher than that in other groups (62.5% vs. 21.4–33.3%, all p <0.05). Inconsistent results between karyotyping and CMA/FISH were observed in 23 cases (19.5%). The risk of pregnancy termination in cases with ultrasound malformations, consistent results, autosomal CM, or a high CM fraction increased with an odds ratio of 3.09, 8.35, 2.30, and 7.62 (all p <0.05). Multiple regression analysis revealed that all four factors were independent risk factors for the termination of pregnancy. Conclusion: Patients with a high fraction of autosomal CM are more likely to have ultrasound malformations. Inconsistent results between different methods in CM are not rare. Ultrasound malformations, consistent results between different methods, autosomal CM, and a high CM fraction were independent risk factors for the choice to terminate pregnancies.
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Mosaic tetrasomy 9p at amniocentesis in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy in various tissues
Article
  • Jan 2023
Objective: We present mosaic tetrasomy 9p at amniocentesis in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy in various tissue. Case report: A 33-year-old primigravid woman underwent elective amniocentesis at 18 weeks of gestation because of anxiety, and the karyotype of cultured amniocytes was 47,XX,+i (9) (p10)[20]/46,XX [55]. Cordocentesis was performed at 20 weeks of gestation, and the karyotype of cord blood was 47,XX,+i (9) (p10)[7]/46,XX [15]. She was referred for genetic counseling at 23 weeks of gestation, and repeat amniocentesis revealed a karyotype of 47,XX,+i (9) (p10)[1]/46,XX [16] with seven cells in one colony having tetrasomy 9p in cultured amniocytes, and in uncultured amniocytes, quantitative fluorescence polymerase chain reaction (QF-PCR) analysis excluded uniparental disomy (UPD) 9 and determined paternal origin of the extra i (9p), array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr 9p24.3p13.1 × 3.0 consistent with 50% mosaicism for tetrasomy 9p, and interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes showed 22.6% (12/53 cells) mosaicism for tetrasomy 9p. A third amniocentesis at 27 weeks of gestation revealed a karyotype of 46, XX (10/10 colonies) in cultured amniocytes, and interphase FISH analysis on uncultured amniocytes revealed 20% (20/100 cells) mosaicism for tetrasomy 9p. The parental karyotypes and prenatal ultrasound were normal. At 39 weeks of gestation, a phenotypically normal 3388-g female baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 47,XX,+idic (9) (q12)[19]/46,XX [21] or 47,XX,+idic (9) (pter→q12:q12→pter)[19]/46,XX [21], 47,XX,+idic (9) (q12)[1]/46,XX [39] and 47,XX,+idic (9) (q12)[4]/46,XX [36], respectively. When follow-up at age two months, the neonate was phenotypically normal, the peripheral blood had a karyotype of 47,XX,+idic (9) (q12)[18]/46,XX [22], and interphase FISH analysis on 100 buccal mucosal cells revealed 1% (1/100 cells) mosaicism for tetrasomy 9p. When follow-up at age seven months, the neonate was phenotypically normal, and the peripheral blood had a karyotype of 47,XX,+idic(9)(q12)[14]/46,XX[26]. Conclusion: Mosaic tetrasomy 9p at amniocentesis can be a transient and benign condition, and can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy in various tissue.
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Clinical and molecular delineation of Tetrasomy 9p syndrome: Report of 12 new cases and literature review
Article
Full-text available
  • Apr 2015
  • AM J MED GENET A
Tetrasomy 9p is a generic term describing the presence of a supernumerary chromosome incorporating two copies of the 9p arm. Two varieties exist: isodicentric chromosome 9p (i(9p)), where the two 9p arms are linked by a single centromeric region, and pseudodicentric 9p (idic(9p)), where one active and one inactive centromere are linked together by a proximal segment of 9q that may incorporate euchromatic material. In living patients, i(9p) and idic(9p) are usually present in a mosaic state. Fifty-four cases, including fetuses, have been reported, of which only two have been molecularly characterized using array-CGH. Tetrasomy 9p leads to a variable phenotype ranging from multiple congenital anomalies with severe intellectual disability and growth delay to subnormal cognitive and physical developments. Hypertelorism, abnormal ears, microretrognathia and bulbous nose are the most common dysmorphic traits. Microcephaly, growth retardation, joint dislocation, scoliosis, cardiac and renal anomalies were reported in several cases. Those physical anomalies are often, but not universally, accompanied by intellectual disability. The most recurrent breakpoints, defined by conventional cytogenetics, are 9p10, 9q12 and 9q13. We report on 12 new patients with tetrasomy 9p (3 i(9p), 8 idic(9p) and one structurally uncharacterized), including the first case of parental germline mosaicism. All rearrangements have been characterized by DNA microarray. Based on our results and a review of the literature, we further delineate the prenatal and postnatal clinical spectrum of this imbalance. Our results show poor genotype-phenotype correlations and underline the need of precise molecular characterization of the supernumerary marker. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
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Mosaic tetrasomy 9p at amniocentesis: Prenatal diagnosis, molecular cytogenetic characterization, and literature review
Article
Full-text available
  • Mar 2014
This study was aimed at prenatal diagnosis of mosaic tetrasomy 9p and reviewing the literature. A 37-year-old woman underwent amniocentesis at 20 weeks' gestation because of advanced maternal age and fetal ascites. Cytogenetic analysis of cultured amniocytes revealed 21.4% (6/28 colonies) mosaicism for a supernumerary i(9p). Repeat amniocentesis was performed at 23 weeks' gestation. Array comparative genomic hybridization, interphase fluorescence in situ hybridization, and quantitative fluorescent polymerase chain reaction were applied to uncultured amniocytes, and conventional cytogenetic analysis was applied to cultured amniocytes. Array comparative genomic hybridization analysis of uncultured amniocytes detected a genomic gain at 9p24.3-9q21.11. Interphase fluorescence in situ hybridization analysis of uncultured amniocytes using a 9p24.3-specific probe RP11-31F19 (spectrum red) showed four red signals in 47.1% (49/104 cells) in uncultured amniocytes. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX, +idic(9)(pter→q21.11::q21.11→pter)[4]/46,XX[20] and 16.7% (4/24 colonies) mosaicism for tetrasomy 9p. Quantitative fluorescent polymerase chain reaction confirmed a maternal origin of tetrasomy 9p. The pregnancy was terminated, and a malformed fetus was delivered with hydrops fetalis and facial dysmorphism. The fetal blood cells had 32.5% (13/40 cells) mosaicism for tetrasomy 9p. Mosaic tetrasomy 9p at amniocentesis can be associated with fetal ascites and hydrops fetalis. The mosaic level of tetrasomy 9p may decrease after long-term tissue culture in amniocytes in case of mosaic tetrasomy 9p.
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Chromosomal Abnormality in Men with Impaired Spermatogenesis
Article
Full-text available
  • Apr 2014
  • INT J FERTIL STERIL
Chromosomal abnormalities and Y chromosome microdeletions are regarded as two most frequent genetic causes associated with failure of spermatogenesis in the Caucasian population. To investigate the distribution of genetic defects in the Romanian population with azoospermia or severe oligozoospermia, karyotype analysis by G-banding was carried out in 850 idiopathic infertile men and in 49 fertile men with one or more children. Screening for microdeletions in the azoospermia factor (AZF) region of Y chromosome was performed by multiplex polymerase chain reaction (PCR) on a group of 67 patients with no detectable chromosomal abnormality. The results of the two groups were compared by a two-tailed Fisher's exact test. In our study chromosomal abnormalities were observed in 12.70% and 8.16% of infertile and fertile individuals respectively. Our data suggests that infertile men with severe azoospermia have higher incidences of genetic defects than fertile men and also patients from any other group. Infertile men with normal sperm present a higher rate of polymorphic variants. It is important to know whether there is a genetic cause of male infertility before patients are subjected to intracytoplasmic sperm injection (ICSI) or testicular sperm extraction (TESE)/ICSI treatment.
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Heteromorphic variants of chromosome 9
Article
Full-text available
  • Apr 2013
Background: Heterochromatic variants of pericentromere of chromosome 9 are reported and discussed since decades concerning their detailed structure and clinical meaning. However, detailed studies are scarce. Thus, here we provide the largest ever done molecular cytogenetic research based on >300 chromosome 9 heteromorphism carriers. Results: In this study, 334 carriers of heterochromatic variants of chromosome 9 were included, being 192 patients from Western Europe and the remainder from Easter-European origin. A 3-color-fluorescence in situ hybridization (FISH) probe-set directed against for 9p12 to 9q13~21.1 (9het-mix) and 8 different locus-specific probes were applied for their characterization. The 9het-mix enables the characterization of 21 of the yet known 24 chromosome 9 heteromorphic patterns. In this study, 17 different variants were detected including five yet unreported; the most frequent were pericentric inversions (49.4%) followed by 9qh-variants (23.9%), variants of 9ph (11.4%), cenh (8.2%), and dicentric- (3.8%) and duplication-variants (3.3%). For reasons of simplicity, a new short nomenclature for the yet reported 24 heteromorphic patterns of chromosome 9 is suggested. Six breakpoints involved in four of the 24 variants could be narrowed down using locus-specific probes. Conclusions: Based on this largest study ever done in carriers of chromosome 9 heteromorphisms, three of the 24 detailed variants were more frequently observed in Western than in Eastern Europe. Besides, there is no clear evidence that infertility is linked to any of the 24 chromosome 9 heteromorphic variants.
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DNA sequence and analysis of human chromosome 9
Article
Full-text available
  • May 2004
Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6–8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.
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Tetrasomy 9p Mosaicism Associated with a Normal Phenotype in Two Cases
Article
Full-text available
  • Apr 2012
  • CYTOGENET GENOME RES
Tetrasomy 9p is a rare chromosomal syndrome and about 30% of known cases exhibit mosaicism. Approximately 50 of the reported cases with tetrasomy 9p mosaicism show a characteristic facial appearance, growth failure, and developmental delay. However, 3 patients with mosaicism for isochromosome 9p and a normal phenotype have also been reported. We report 2 additional cases of clinically normal young females with tetrasomy 9p mosaicism, one of whom also exhibited X chromosome aneuploidy mosaicism leading to an overall of 6 different cell lines. STR analysis performed on this complex mosaic case indicated that the extra isochromosome was of maternal origin while the X chromosome aneuploidy was of paternal origin, indicating a postzygotic event.
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Cytogenetics of Premature Ovarian Failure: An Investigation on 269 Affected Women
Article
Full-text available
  • Jan 2011
  • J BIOMED BIOTECHNOL
The importance of X chromosome in the aetiology of premature ovarian failure (POF) is well-known but in many cases POF still remains idiopathic. Chromosome aneuploidy increase is a physiological phenomenon related to aging, but the role of low-level sex chromosome mosaicism in ovarian function is still undiscovered. Standard cytogenetic analysis was carried out in a total of 269 patients affected by POF: 27 chromosomal abnormalities were identified, including X chromosome and autosomal structural and numerical abnormalities. In 47 patients with 46,XX karyotype we performed interphase FISH using X alpha-satellite probe in order to identify X chromosome mosaicism rate. Aneuploidy rate in the patient group was significantly higher than the general population group. These findings underline the importance of X chromosome in the aetiology of POF and highlight the potential role of low-level sex chromosome mosaicism in ovarian aging that may lead to a premature onset of menopause.
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Unclassifiable pattern of hypopigmentation in a patient with mosaic partial 12p tetrasomy without Pallister-Killian syndrome
Article
  • May 2017
  • AM J MED GENET A
Pallister-Killian syndrome (PKS-#OMIM601803) is a multisystem developmental disorder typically due to the presence of an aneuploidy cell line, consisting of a supernumerary tetrasomic chromosomal marker (SCM) arisen from the short arm of chromosome 12 (12p isochromosome). The clinical phenotype, which is strictly related to the percentage and tissue distribution of aneuploid cells, is characterized by craniofacial dysmorphisms, pigmentary skin anomalies, limb shortening, congenital heart defects, diaphragmatic hernia, hypotonia, intellectual disability, and epilepsy. We report on a 4 year-old girl harboring a 12p partial isochromosome, involving the PKS critical region, affecting about 70% of circulating lymphocytes, urine, and saliva cells and fibroblast from a hyperpigmented skin spot, and 100% of fibroblasts from a hypopigmented skin spot. Interestingly, despite the high proportion of affected cells this patient did not present with PKS, and a pattern of linear and patchy pigmentary mosaicism was the sole clinical manifestation. The present observation suggests that partial 12p SCM can also result in mild phenotypes, and its prevalence in the human population could have been underestimated. Accurate dermatologic evaluation could be a major handle for genetic testing.
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T�trasomie partielle du chromosome 9, � l'�tat de mosa�que, chez un enfant porteur de malformations multiples
Article
  • Jan 1973
Le cas d'un enfant porteur de malformations multiples est dcrit. L'tude des chromosomes par les techniques du Q-, G-, C- et Giemsa-11 banding a rvl que les lymphocytes du proposant prsentaient une formule caryologique 47XY,t(9p,h+,9p) alors que les fibroblastes provenant d'une biopsie de peau taient normaux (46XY).The case of a child showing multiple malformations is reported. Chromosome studies by Q, G, C and Giemsa 11 banding methods revealed that lymphocytes of the propositus had a 47XY,t(9p,h+,9p) karyotype though fibroblasts from a skin biopsy were normal (46XY).Es wird ber ein Kind, das mannigfaltige Mibildungen zeigt, berichtet. Die Chromosomenuntersuchung mit Hilfe der Q-, G-, C- und Giemsa-11 Banding-Methoden hat an Lymphocyten den Karyotyp 47,XY,t(9p,h+,9p) ergeben, whrend Fibroblasten von einer Hautbiopsie einen normalen Karyotyp (46,XY) haben.
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