CYTOGENETIC EXAMINATIONS IN THE HEALTH CARE SYSTEM:...

Journal of Health Policy, Insurance and Management – Polityka Zdrowotna 37

Cytogenetic examinations in the health care system: their potential role in prevention of diseases

CYTOGENETIC EXAMINATIONS IN THE HEALTH CARE SYSTEM: THEIR POTENTIAL ROLE IN PREVENTION OF DISEASES

Badania cytogenetyczne w aspekcie klinicznym w ochronie zdrowia. Potencjalne znaczenie profilaktyczne

AbstrAct

Chromosomal aberrations belongs to the group of the most frequent causes of infertility, congenital defects, mental retardation, and sex determination disorders.

Identification of numerical and structural chromosome aberrations allows for pre- and postnatal diag-nosis and thus for genetic counseling focused both on the patient and the patient’s family.

The present paper discusses the importance of cytogenetic examinations in the diagnosis and manage-ment of 1) infertility and reproductive failure, 2) fetal defects (prenatal diagnosis), 3) congenital defects and mental retardation syndromes, as well as 4) the methodological foundation of laboratory cytogenetic diagnosis.

Keywords: cytogenetic studies, karyotype, infertility, miscarriage, prenatal diagnosis, congenital defects

Słowa kluczowe: badania cytogenetyczne, kariotyp, niepłodność, poronienia, badania prenatalne, wady wrodzone

IntroductIon

With advances in medical knowledge, genetics, and molecular biology, it has become clear that a large proportion of human diseases are linked to genetic alterations.

Apart from diseases with purely genetic etiol-ogy, such as chromosomal aberration syndromes and conditions due to single gene mutations, many disorders are caused by a combination of genet-ic and environmental factors, such as arterial hypertension and diabetes. There are also a num-ber of conditions that are almost entirely caused by external factors, such as congenital cytomeg-alovirus infection or trauma.

Genetic diseases may result from a change (aberration) in the number and/or structure of chromosomes, mutations in single genes, or defects involving many genes and detrimental external factors.

Chromosomal aberrations are most frequently manifested by clinical symptoms such as dysmorphic features, congenital defects, and impaired sexual,

motor or intellectual development. In clinical prac-tice, a frequently used term is “chromosomal phe-notype,” which suggests a known or undetermined chromosomal rearrangement as etiological factor.

The identification of chromosomal aberrations in a patient enables physician to make a diagnosis and probable prognosis, and to determine further diagnostic, therapeutic, and rehabilitation proce-dures. It also serves as the basis for offering genet-ic advice to the patient and his or her family. This also includes pre-conception counseling and eval-uation of the risk of recurrence of the same disorder, as well as prenatal consultations. Thus, cytogenetic tests constitute an element of:• First-line prevention of chromosomal aberra-

tions, mostly through in vitro fertilization with preimplantation genetic diagnosis;

• Second-line prevention – early diagnosis of chromosomal aberrations enables imple-mentation of optimum further diagnostic pro-cedures and thus therapeutic management;

Agnieszka Stembalska, Ryszard Ślęzak, Robert Śmigiel, Maria Małgorzata Sąsiadek* Wroclaw Medical University

* All authors equally contributed to the paper.

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• Third-line prevention (early support, physi-cal therapy, etc.) – early diagnosis, treatment, or physical therapy makes it possible to prevent complications linked to existing disorders. Due to the fact that the clinical consequences

of chromosomal aberrations may emerge at any time of life, this paper adopts the following chro-nology of the presented issues: 1) infertility and reproductive failure;2) defects due to chromosomal aberrations dur-

ing prenatal development;3) defects in newborns and children;4) concise information about cytogenetic testing

methods.

cytogenetIc tests In couples

WIth reproductIve fAIlure

Reproductive failure, which constitutes a seri-ous problem in contemporary gynecology, may be caused by conception and/or pregnancy failure. Chromosomal aberrations (changes in the number and/or structure of chromosomes) constitute one of the most frequent factor impairing conception (also assisted conception), leading to early or late spontaneous abortions, and causing congenital disorders.

Indications for cytogenetic testing of both partners include failure to conceive (also in the case of in vitro fertilization), two or more sponta-neous abortions, or giving birth to a child with con-genital defects. In this group of patients, the most frequent chromosomal changes do not involve a loss or/and addition of chromosome fragments, but are balanced and include reciprocal chromo-somal translocations, including Robertsonian translocations and chromosomal inversions,. Carriers of balanced chromosomal aberrations are healthy, but they may transfer an unbalanced aberration to their offspring. This risk depends on the course of meiosis, including crossing over,

and the survival rate of fetuses with an unbal-anced karyotype. Knowledge of the mechanisms of such chromosomal aberrations forms the basis for evaluation of the risk of miscarriage or con-genital disorders in the fetus.1 If a person is diag-nosed as a carrier of a balanced chromosomal translocation, a pedigree analysis should be done an thus probable carriers of balanced transloca-tion should be identified. Evaluation of the risk of giving birth to a child with an unbalanced aber-ration, or the risk of miscarriage or fetal death/still birth in the next pregnancy is conducted on the basis of pedigree analysis using direct methods (only in families where many relatives have been diagnosed as carriers) or indirect meth-ods (grouping of pedigrees of families in which unbalanced translocations appeared in respect of the same chromosomal break-point localiza-tion). To assess risk by the indirect method, one needs to have access to databases containing information on families with chromosomal trans-locations. The Polish Collection of Reciprocal Chromosomal Translocations is maintained by the Genetics Department, Medical University of Białystok. Detecting an aberration in one of the parents is an indication for conducting invasive prenatal tests in each pregnancy. Some patients may consider in vitro fertilization with preim-plantation genetic diagnosis. This method allows for determining the karyotype of the embryo even prior to implanting it in the uterus. Examination of a single cell from a blastocyst (usually one cell is taken from an 8- or 16-cell blastocyst) allows for choosing embryos with normal karyotype (normal set of chromosomes). This procedure lies within first-line prevention (prevention of chromosomal aberrations in the fetus). Preimplantation cytoge-netic tests are most often carried out using in situ fluorescence (FISH) or comparative genomic hybridization (CGH).2

Agnieszka Stembalska, Ryszard Ślęzak, Robert Śmigiel, Maria Małgorzata Sąsiadek

1 Sąsiadek M M, Haus O, Łukasik-Majchrowska M, Ślęzak R, Paprocka-Borowicz M, Busza H, Plewa R, Bułło A, Jagielski J. Badania cytogenetyczne u małżeństw z poronieniami samoistnymi. Ginekologia Polska (5a). 1997: 248-252; Pasińska M, Haus O, Skonieczka K, Ślęzak R, Midro AT, Stasiewicz-Jarocka B, Szczepaniak M, Adamc-zak R, Marcinkowska A, Bartusiak K. Wyniki badań cytogenetycznych i molekularnych u 35 par z niepłodnością pierwotną. Wiadomości Lekarskie (1-2). 2006: 38-43.

2 Le Caignec C, Spits C, Sermon K, De Rycke M, Thienpont B, Debrock S, Staessen C, Moreau Y, Fryns J P, Van Steirteghem A, Liebaers I, Vermeesch J R. Single-cell chromosomal imbalances detection by array CGH. Nu-cleic Acids Res (e68). 2006: 34; Schoolcraft WB, Katz-Jaffe MG, Stevens J, Rawlins M, Munne S. Preimplantation aneuploidy testing for infertile patients of advanced maternal age: a randomized prospective trial. Fertility and Sterility (92). 2009: 157-162.


1.1. Cytogenetic examinations in fetal loss.

Miscarriages are most often caused by numerical chromosomal aberrations, arising de novo. Chromosomal changes are found in 50%-60% of early and in about 10% of late fetal losses.3 It is thought that most miscarriages before the 10th week of pregnancy are linked to non-inherited numerical chromosomal aberrations which arise as a result of chromosome nondisjunction (non-sep-aration) in male or female gametes. In such cases trisomy of chromosomes 13, 16, 18, 21, 22, and X or monosomy of chromosome X are most frequent. The trisomy are usually lethal. Among them tri-somy of chromosomes 16 and 22 most frequently observed, while fetuses with trisomy 13, 18, and 21 are sometimes born alive. Cytogenetic examina-tions of pregnancy lost samples are now conducted by molecular cytogenetic methods, and especially FISH and CGH. They enable fast and reliable determination of a numerical chromosomal aber-ration, confirming or ruling out such an aberration as the cause of the miscarriage. They also make it possible to prepare reliable genetic counseling for parents including an information what should be done to establish risk of recurrence of an aber-ration in the next pregnancy and plan for an ade-quate pre-conception and prenatal diagnostics.4

1.2 Cytogenetic examinations in primary infertility

Numerical chromosomal aberrations are found only in a minority (7-10%) of couples presenting at genetic clinics due to reproductive failure. These cases usually include males with previously undi-agnosed Klinefelter syndrome and females with trisomy X. If a cytogenetic test reveals additional chromosomes X in a male, this usually implies azoospermia. However, in some of these patients spermatogenesis may be partially preserved, which allows for extraction of reproductive cells (spermatids, spermatocytes, or sperm cells) from the testicle and use them for in vitro fertilization.

Other causes of spermatogenesis disorders, including azoospermia, are balanced aberrations between chromosome Y and autosomal chromo-somes or between some autosomes (mostly acro-centric chromosomes). The presence of an addi-tional chromosome X in the female karyotype usu-ally does not obviously lead to phenotypic defects, but is often linked to the risk of premature ovarian failure. Therefore, detection of trisomy X provides the female patient with important information con-cerning a potential procreation disorder.5

1.3. Cytogenetic diagnostics in sex determination and differentiation disorders

The most frequent causes of sex determi-nation disorders in women are structural and/or numerical aberrations of chromosomes X lead-ing to Turner syndrome (TS). In about 60% of TS cases monosomy of chromosome X, in 5% mosa-icism with the presence of additional cell lines containing a different sex chromosome, and in the other cases – structural aberrations of chromo-some X are observed.

In TS patients the age at which the patient is diagnosed is of critical importance for the final outcome of treatment. Analysis of the age of women diagnosed with TS shows that several years ago diagnoses were most often made at age 17-21 on the basis of the absence of menarche and characteristic dysmorfic features. Today, such a diagnosis is usually made for patients at about 3-4 years of age, presenting developmental delay (a height below 3 centile), thus allowing for early therapy. The key to success in treating most of dys-morfic features, including short stature in TS girls is an early treatment with growth hormone (pri-or to closure of epiphyseal cartilage) preventing short stature and introduction of estrogen-gesta-gen replacement therapy. Otherwise, dysmorfic features of TS may pose a problem in social rela-tions and lead to lower self-esteem of the patients (psychosocial consequences).6

Cytogenetic examinations in the healthcare system: their potential role in prevention of diseases

3 Lebedev I. Mosaic aneuploidy in early fetal losses, Cytogenetics and Genome Research (133). 2011: 169-183.4 Dutta U R, Rajitha P, Pidugu V K, Dalal A B. Cytogenetic abnormalities in 1162 couples with recurrent miscar-

riages in Southern region of India: report and review. J Assist Reprod Genet (28). 2011: 145-149; Branch D W, Gibson M, Silver R M. Recurrent miscarriage. New England Journal of Medicine (363). 2010: 1740-1747.

5 Otter M, Schrander-Stumpel C, Curfs L. Triple X syndrome: A review of the literature. European Journal of Hu-man Genetics (18). 2010: 265-271.

6 Ślęzak R. Propozycje postępowania diagnostycznego w zespole Turnera. Biuletyn Informacyjny Komisji Gene-tycznej Człowieka (7). 2001: 51-52. Ślęzak R, Sąsiadek M, Dobosz T, Gogulska L, Jagielski J. Oznaczanie swoistych sekwencji chromosomu Y w zespole Turnera. Ginekologia Polska (9). 1999: 610-616.

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Moreover, an early diagnosis of TS makes it possible to initiate wide-ranging preventive and curative management, including treatment of con-genital anomaly linked to TS, and especially malformation of the urinary tract (often asymp-tomatic), cardiovascular system, and hypothy-roidism. An important aspect of preventive man-agement in TS patients is exclusion of the pres-ence of Y chromosome sequences which, under the circumstances, are related to increased risk of cancer of dysplastic gonads.7 Early gonadecto-my may prevent development of gonadoblastoma or dysgerminoma.

Anti-cancer prevention is used in every case where the patient’s phenotype is female and a cyto-genetic test has revealed the presence of chromo-some Y, as well as in pure and mixed gonadal dys-genesis, and insensitivity to androgens.

Cytogenetic examinations constitute a very important tool in differential diagnostics in cases of alterations in external genitals in newborns (especially in the case of ambiguous genitalia).

Suspected adrenal hyperplasia syndrome and virilizing tumors require, along with hormonal, biochemical, and molecular tests, prompt cytoge-netic diagnostics for determining the newborn’s chromosomal sex. This is necessary for entering the right sex in the birth certificate and also for making the parents aware of the need to conduct plastic surgery of external sex organs in the child.8

cytogenetIc exAMInAtIons In prenAtAl dIAgnostIcs

Prenatal cytogenetic examinations are part of second-line prevention, that is, they are aimed at early detection (before birth, and often before the third trimester of gestation) of genetic disor-ders. Thus, the pregnant woman may be given an adequate health care, including intrauterine fetus therapy (treating or reducing the effects of the diagnosed defect, if possible) and appropri-ate specialized care for newborn (in some cases palliative care).9 If serious and irreversible defects in the fetus are diagnosed, the parents may also decide to terminate the pregnancy.10

The frequency of chromosomal aberrations at the time of conception amounts to as much as 40%, but over the course of pregnancy the number of fetuses with chromosomal aberrations decreases due to the high rate of spontaneous abortions. Thus, such aber-rations occur in only about 0.5% of newborns.11

All methods of collecting cells from the fetus are fraught with a risk of complications, mostly miscarriage (about 1% in amniocentesis and cho-rionic villus sampling and about 2% in cordocen-tesis).12 Therefore, such tests should be offered only in the case of medical indications, such as:13 • Woman,s age at conception over 35 years

(or >40 according to the Polish Gynecological Society, 2009) due to increased risk of trisomy 13, 18, or 21 in the offspring;


7 Baka-Ostrowska M. Noworodek z obojnaczymi narządami płciowymi. Przegląd Chirurgii Dziecięcej (4). 2009: 123-129.8 Stembalska A, Łaczmańska I, Dudarewicz L. Nieinwazyjne badania prenatalne w diagnostyce aneuploidii

chromosomów 13, 18 i 21 – aspekty teoretyczne i praktyczne. Ginekologia Polska (2). 2011: 126-132; Dangel T. Wady letalne u noworodków, opieka paliatywna jako alternatywa wobec aborcji i uporczywej terapii. Standardy Medycyny (9). 2007: 108-110; Pergament E. First-Trimester Genetic Counseling: Perspectives and Considerations. Clinics in La-boratory Medicine (30). 2010: 557-563; Sharma G, McCullough L B, Chervenak FA. Ethical considerations of early (first vs. second trimester) risk assessment disclosure for trisomy 21 and patient choice in screening versus diagnostic testing. American Journal of Medical Genetetics Part C Seminars in Medical Genetetics (145C). 2007: 99-104.

9 Ustawa o planowaniu rodziny, ochronie płodu ludzkiego i warunkach dopuszczalności przerywania ciąży z dnia 7 stycznia 1993 r. (z 1993 r., Dz.U. Nr 17, poz. 78; z 1995 r., Nr 66, poz. 334, z 1996 r., Nr 139, poz. 646, z 1997 r. Nr 141, poz. 943, Nr 157, poz. 1040 i z 1999 r. Nr 5, poz. 32).

10 Branch D W, Gibson M, Silver R M. Op. cit.; Lebedev I. Mosaic aneuploidy in early fetal losses, Cytogenetics and Genome Research (133), 2011; Zhang L, Zhang X-H, Linag M Y, Ren M H. Prenatal cytogenetic study of 2782 cases of high-risk pregnant women. Chinese Medical Journal (123). 2010: 423-430.

11 Stembalska A, Łaczmańska I, Dudarewicz L. Op. cit.; Ball R H. Invasive fetal testing. Current Opinion in Ob-stetrics and Gynecology (16). 2004: 159-162.

12 Stembalska A, Łaczmańska I, Dudarewicz L. Op. cit.; Stembalska A, Ślęzak R, Pesz K, Gil J, Sąsiadek M M. Prenatal diagnosis - principles of diagnostic procedures and genetic counseling. Folia Histochemica et Cytobiologica (45) Sup-plement 1. 2007: 11-16; Stembalska A, Ślęzak R, Sąsiadek M. Badania prenatalne. Family Medicine and Primary Care Review (1). 2005: 18-24; Ślęzak R, Florjański J, Zalewski J, Sąsiadek M, Heimrath J. Diagnostyka prenatalna triploidii. Ginekologia Polska (4). 2005: 295-299; Anderson C L, Brown C L. Fetal chromosomal abnormalities: Antenatal screen-ing and diagnosis (79). AFP 2009: 117-123; Gil J, Pesz K, Sąsiadek M M, Stembalska A, Ślęzak R. Genetyczna diag-nostyka prenatalna, metody badań, elementy poradnictwa genetycznego. Badania Diagnostyczne (7-8). 2008: 41-44.

13 Rekomendacje Polskiego Towarzystwa Ginekologicznego dotyczące postępowania w zakresie diagnostyki prena-talnej. Opracowanie zespołu ekspertów. Ginekologia Polska (80), 2009: 390-394.


• numerical or structural chromosomal aberra-tion in previous fetuses or children;

• congenital defects that may have been caused by chromosomal aberrations found in previous fetuses or children (whether stillborn or live born);

• either of the partners is a carrier of a clinically significant balanced chromosomal aberration, because this increases the risk of having off-spring with an unbalanced karyotype;

• abnormal results of non-invasive prenatal examinations (ultrasound) and/or biochemi-cal screening tests, giving rise to a suspicion of chromosomal aberration in the fetus.

Women who meet at least one of the above indications for a cytogenetic examination of the fetus belong to a high risk group in terms of giving birth to a child with congenital disorders and fall under the Prenatal Testing Program in Poland.14

Genetic prenatal counseling is non-directive, and is only of informative nature (explaining, completing, and verifying data). The final deci-sion as to whether or not to conduct such a test is always made by the pregnant woman.15

genetIc dIAgnostIcs In congenItAl dIsorders And dysMorphIc syndroMes

Over the past several decades, an increas-ing proportion of children have been hospitalized at pediatric units or seen at outpatient facilities due to congenital disorders. Thus, these disorders constitute a serious clinical (and diagnostic) prob-lem, as well as a major social and economic issue.

Patients with these disorders often present with a complicated history and treatment may not bring the desired medical or social effects.16

Congenital disorders occur in about 2-3% of live born children, out of which 25-35% is linked to chromosomal aberrations. The inci-dence of aberrations diagnosed in live born chil-dren increases with progress of genetic tech-niques and higher sensitivity of cytogenetic and molecular tests.17 Indications for cytogenetic tests in patients with congenital disorders include the following clinical situations:18

1) presence of phenotypic features characteristic of a specific chromosomal syndrome;

2) presence of multiple developmental defects and/or dysmorphic features;

3) delayed psychomotor development or mental retardation, especially if accompanied by dys-morphic features;

4) abnormal sexual maturation (absent or too early);

5) abnormal appearance of external genitalia; 6) menstruation disturbances of unknown

etiology;7) short stature in girls;8) suspicion of a chromosomal instability

syndrome. If a chromosomal aberration is identified

as a cause of a congenital disorder in a child, then thorough advice should be given containing infor-mation about the course of the disease and any related congenital defects. This enables extensive early clinical diagnostics (e.g., to detect a heart defect) and preventive care by specialized physi-cians (e.g., a physiotherapist, speech therapist,


14 Stembalska A, Łaczmańska I, Dudarewicz L. Op. cit.; Stembalska A, Ślęzak R, Pesz K, Gil J, Sąsiadek M M. Op. cit.; Stembalska A, Ślęzak R, Sąsiadek M. Op. cit.

15 Latos-Bieleńska A, Materna-Kiryluk A (ed.). i Zespół ds. PRWWR (Polski rejestr Wad Wrodzonych): Wrodzone wady rozwojowe w Polsce w latach 2005-2006. Dane z Polskiego Rejestru Wrodzonych Wad Rozwojowych. OWN. Poznań 2010; Śmigiel R, Ślęzak R, Łaczmańska I, Bateraj-Kubicka B, Bąk E. Zespół Emanuel u noworodka jako skutek rodzinnej, niezrównoważonej translokacji między chromosomami 11 i 22. Pediatria Polska (12). 2005: 1126-1132.

16 Latos-Bieleńska A, Materna-Kiryluk A (ed.). Op. cit.17 Ślęzak R, Strzałkowska A, Czemarmazowicz H, Skulimowska G, Matthews-Brzozowska T. Podwójna trisomia

częściowa chromosomów 2 i 14 u dziecka z zespołem cech dysmorficznych. Pediatria Polska (4). 2006: 293-297; Ślęzak R, Łaczmańska I, Busza H, Czemarmazowicz H. Mozaikowa postać częściowej trisomii (de novo) ramion krótkich chromosomu 12 u dziecka z licznymi cechami dysmorficznymi - opis przypadku. Pediatria Polska (8). 2005: 697-700; Ślęzak R, Florjański J, Zalewski J, Sąsiadek M, Heimrath J. Op. cit.; Śmigiel R, Ślęzak R, Łaczmańska I, Bateraj-Kubicka B, Bąk E. Op. cit.; Jacobs P A, Browne C, Gregson N, Joyce C, White H. Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. Medycyna Genetyczna (29). 1992: 103-108.

18 Śmigiel R, Stembalska A. Niepełnosprawność intelektualna uwarunkowana genetycznie - wybrane aspekty. Nowa Pediatria (R.11). 2007: 89-96; Borg K, Bocian E, Bernaciak J, Nowakowska B, Derwich K, Obersztyn E, Szczałuba K, Śmigiel R, Kostyk E, Mazurczak T. Zrównoważone rearanżacje chromosomowe jako przyczyna niepełnosprawności intelektualnej. Analiza 22 przypadków z wykorzystaniem technik CGH oraz FISH. Medy-cyna Wieku Rozwojowego (13). 2009: 81-93.

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psychologist, neurologist, ophthalmologist). If the chromosomal aberration identified in the child is heritable, then other members of the family may be tested, following pedigree analysis. In this way, examination of a child with a congenital disorder may be a point of departure for genet-ic testing of the entire family, as well as genetic counseling, possibly including indications for prenatal testing.19 The current algorithm for cyto-genetic diagnostics in congenital disorders and mental retardation involves, first of all, exclusion of chromosomal aberrations using classical cyto-genetic methods (e.g., G-bands by trypsin using Giemsa, GTG), molecular cytogenetic methods such as fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), fol-lowed by molecular methods such as multiplex ligation-dependent probe amplification (MLPA). Diagnostics of chromosomal instability syn-dromes, with symptoms including both congeni-tal defects and mental retardation, is particularly difficult. In cytogenetic diagnostics of such syn-dromes, it is necessary to use special reagents stimulating chromosomal instability: bleomycin, diepoxybutan, or X-radiation.

cytogenetIc exAMInAtIon Methods And MAterIAl

Cytogenetic examinations involve evalua-tion of the structure and number of chromosomes (classical cytogenetics, molecular cytogenetics). The most frequently used classical cytogenetic method, G bands by trypsin using Giemsa (GTG), enables the detection of numerical chromosomal

aberrations and structural changes of a size of 2-7 × 106 base pairs (bp).20

Molecular cytogenetic methods are used for detecting smaller chromosomal aberrations (microaberrations). These include FISH using probes hybridizing with specific regions, which makes it possible to detect changes in the range of 40–250 kbp. However, this technique requires a precise clinical diagnosis.21 An alternative tech-nique for examining unbalanced microaberrations is MLPA, which allows for the detection of a dele-tion and duplication of individual exons and ena-bles evaluation of up to over forty different loci during one reaction.22

CGH, known as molecular karyotyping, allows for the detection of structural changes of the order of 3 Mbp. Its sensitivity may be greatly enhanced by using microarrays (array-CGH), which enables the detection of microaberrations in the range of 1 Mbp to 15 kbp.23

FISH, CGH and MLPA may also be used for detecting numerical chromosomal aberrations.

In the case of couples presenting with repro-ductive failure as well as children and adults with congenital disorders and/or intellectual retarda-tion, the material typically used for cytogenetic examinations consists of peripheral blood lym-phocytes. In prenatal cytogenetic examinations, specimens include trophoblast cells (trophoblast biopsy in the 10th-14th week of pregnancy), amni-otic fluid cells (amniocentesis in the 15th-19th week of pregnancy), or cord blood lymphocytes (cor-docentesis after the 19th week of pregnancy).24 In the case of some genetic disorders, it may be useful to acquire other tissues for cytogenet-ic examination, e.g., skin fibroblasts (in the case


19 Kozłowska J, Łaczmańska I. Badania cytogenetyczne i molekularne wykorzystywane w diagnostyce chorób uwarunkowanych genetycznie. Diagnostyka Laboratoryjna (44). 2008: 379-382.

20 Palomares M, Delicado A, Lapunzina P, Arjona D, Amiñoso C, Arcas J, Martinez Bermejo A, Fernández L, López Pajares I. MLPA vs multiprobe FISH. comparison of two methods for the screening of subtelomeric rear-rangements in 50 patients with idiopathic mental retardation. Clinical Genetics (69). 2006: 228-233.

21 Łaczmańska I, Łaczmański Ł. Metoda MLPA oraz jej zastosowanie w diagnostyce chorób uwarunkowanych gene-tycznie. Postępy Biologii Komórki (36). 2009: 555-565; Palomares M, Delicado A, Lapunzina P, Arjona D, Amiño-so C, Arcas J, Martinez Bermejo A, Fernández L, López Pajares I. Op. cit.; Kozłowska J, Łaczmańska I. Op.cit.

22 Śmigiel R, Stembalska A. Op. cit.; Kozłowska J, Łaczmańska I. Op. cit.; Kutkowska-Kaźmierczak A, Obersztyn E, Helias-Rodzewicz Z, Bocian E, Mazurczak T. Subtelomeric aberration as a cause of severe somatic and psy-chomotor retardation in a child with dysmorphic features and CNS defects. Medycyna Wieku Rozwojowego (8). 2004: 949-962; Coe B P, Ylstra B, Carvalho B, Meijer GA, Macaulay C, Lam W L. Resolving the resolution of array CGH. Genomics (89). 2007: 647-653.

23 Łaczmańska I, Stembalska A, Ślęzak R, Kozłowska J, Makowska I, Czemarmazowicz H, Pesz K A, Śmigiel R, Jakiel A, Sąsiadek M M. Rapid-FISH jako szybka metoda wykrywania najczęstszych liczbowych aberracji chromosomow-ych w diagnostyce prenatalnej u kobiet z grupy wysokiego ryzyka. Ginekologia Polska (12). 2007: 952-955; Gil J, Pesz K, Sąsiadek M M, Stembalska A, Ślęzak R. Op. cit.; Stembalska A, Ślęzak R, Pesz K, Gil J, Sąsiadek M M. Op. cit.


of a suspected chromosomal mosaic, such as the Pallister–Killian syndrome, which is caused by the occurrence of tetrasomy and/or trisomy of chromosome 12p in a mosaic), gonadal tissue in some sex determination disorders, and tropho-blast or fetal tissues in the case of aborted fetuses.

suMMAry

The identification of chromosomal aberra-tions is important not only with a view to giving the patient a correct prenatal or postnatal diagno-sis and implementing adequate therapeutic and preventive management; it also enables the iden-tification of carriers of chromosomal aberrations in the patient’s family, who may then be provided with appropriate health hare.

references

1. Anderson C L, Brown C L. Fetal chromosomal abnormalities. antenatal screening and diagnosis (79). American Family Physician 2009.

2. Baka-Ostrowska M. Noworodek z obojnaczy-mi narządami płciowymi. Przegląd Chirurgii Dziecięcej (4). 2009.

3. Ball R H. Invasive fetal testing. Current Opinion in Obstetrics and Gynecology (16). 2004.

4. Borg K, Bocian E, Bernaciak J, Nowakowska B, Derwich K, Obersztyn E, Szczałuba K, Śmigiel R, Kostyk E, Mazurczak T. Zrównoważone rearanżacje chromosomowe jako przyczyna niepełnosprawności intelektualnej. Analiza 22 przypadków z wykorzystaniem technik CGH oraz FISH. Medycyna Wieku Rozwojowego (13). 2009.

5. Branch D W, Gibson M, Silver R M. Reccurent miscarriage. New England Journal of Medicine (363). 2010.

6. Coe B P, Ylstra B, Carvalho B, Meijer G A, Macaulay C, Lam W L. Resolving the resolution of array CGH. Genomics (89). 2007.

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