Conventional G-banding Analysis Research Articles

Prenatal detection of chromosome 7q deletion with duplication: A case report and literature review.

With advances in prenatal diagnostic techniques, chromosomal microdeletions and microduplications have become the focus of prenatal diagnosis. 7q partial monosomy or trisomy due to a deletion or duplication of the 7q end is relatively rare and usually originates from parents carrying a balanced translocation. Noninvasive prenatal screening (NIPT) showed a fetus with partial deletion and duplication of chromosome 7q. It was not possible to determine whether the fetus was normal. Conventional chromosome G-banding and chromosome microarray analysis (CMA) were performed on fetal amniotic fluid samples and parental peripheral blood samples. The pregnant women were given detailed genetic counseling by clinicians. The fetal karyotype was 46, XY on conventional G-banding analysis. The CMA test results showed a deletion of approximately 7.8 Mb in the 7q36.1q36.3 region and a duplication of 6.6Mb in the 7q35q36.1 region. The parents' karyotype analysis and CMA results were normal, indicating a new mutation. CMA molecular diagnostic analysis can effectively detect chromosomal microdeletions or microduplications, clarify the relationship between fetal genotype and clinical phenotype, and provide a reference for prenatal diagnosis of chromosomal microdeletion-duplication syndrome.

Clinical features and genetic analysis of two fetuses with ring chromosome 21 mosaicism

To investigate the perinatal clinical phenotype and genetic characteristics of two fetuses with ring chromosome 21 mosaicisms. Two fetuses who were diagnosed at the Xiamen Maternal and Child Health Care Hospital in November 2021 were selected as the study subjects. Clinical data of the two fetuses were collected. Conventional G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out for the fetuses and their parents. Prenatal ultrasonography of fetus 1 has revealed absence of nasal bone, ventricular septal defect, persistent left superior vena cava, and mild tricuspid regurgitation. Chromosomal karyotyping was 46,X?,dic r(21;21)(p12q22;q22p12)[41]/45,X?,-21[9]. CMA has revealed a 30.00 Mb quadruplication at 21q11.2q22.3 and a 3.00 Mb deletion at 21q22.3. For fetus 2, ultrasonography has revealed pointed echo of the nasal bone. The fetus was found to have a karyotype of 46,X?,r(21)(p12q22)[83]/45,X?,-21[14]/46,X?,dic r(21;21)(p12q22;q22p12)[3]. CMA has revealed a 5.10 Mb quadruplication at 21q22.12q22.3 and a 2.30 Mb deletion at 21q22.3. The perinatal phenotype of the two fetuses with ring chromosome 21 mosaicisms is related to the duplication of chromosomal segments near the breakpoints of the chromosomal deletions. The combined chromosomal karyotyping and CMA has enabled prenatal diagnosis and genetic counseling for these families.

Genetic analysis of an infant with rare type of trisomy 21 syndrome

To investigate the genetic cause for an infant with mental retardation through molecular cytogenetic analysis. Conventional G-banding analysis of peripheral blood for the family was first conducted. Chromosomal microarray analysis (CMA) was performed to further ascertain the size and origin of the abnormal chromosome fragments of the patient. We identified a Chinese infant who carries an unbalanced, maternally inherited karyotype 48, XY, +der(X) (Yqter→Yq11.221∷Xp22.31→Xqter), +21 in which karyotype and CMA analyses disclosed Xp22.31→Xqter duplication of 147.3 Mb and Yq11.221→Yq11.23 duplication of 12.7 Mb. Accompany with cytogenetic analysis, CMA can accurately identify the origin and size of the abnormal chromosomes, contributing to the precisely genetic analysis.

Chromosomal copy number analysis of products of conception by conventional karyotyping and next-generation sequencing.

PurposeChromosomal abnormalities are a major cause of spontaneous abortion, and conventional G‐banded karyotyping (G‐banding) is mainly utilized for chromosomal analysis. Recently, next‐generation sequencing (NGS) has been introduced for chromosomal analysis. Here, we aimed to investigate the applicability and utility of NGS‐based chromosomal analysis of products of conception (POC) on chorionic villus samples from spontaneous abortion.MethodsThe results of chromosomal analysis of 7 chorionic villus samples from spontaneous abortion were compared between conventional G‐banding and NGS‐based chromosomal copy number analysis. Age dependency and frequency of each chromosomal aneuploidy were evaluated for 279 cases analyzed by NGS.ResultsExcluding two cases (culture failure and maternal cell contamination), the results were consistent between G‐banding and NGS. For cases analyzed by NGS, the rate of chromosomal abnormality increased in a maternal age‐dependent manner. The frequency of each chromosomal aneuploidy detected by NGS was almost the same as that previously reported. Finally, NGS analysis was possible for difficult cases by G‐banding analysis, such as culture failure, maternal cell contamination, long‐term storage cases, and low cell number.ConclusionsChromosome analysis using NGS not only obtains comparable results to conventional G‐banding, but also can analyze POC more accurately and efficiently.

TP53 State Dictates Genome Stability, Clinical Presentation and Outcomes in Myelodysplastic Syndromes

TP53 State Dictates Genome Stability, Clinical Presentation and Outcomes in Myelodysplastic Syndromes

29. CHROMOSOMAL COPY NUMBER ANALYSIS OF CHORIONIC VILLUS FROM SPONTANEOUS ABORTION BY NEXT GENERATION SEQUENCING

Introduction Chromosomal abnormalities are the most common reason for spontaneous abortion. Conventional cytogenetic analysis by G-banded karyotyping is generally performed for chromosomal analysis, but it has a problem with low-resolution, and is needed long term cell culture and enough experience for diagnosis. More recently, next generation sequencing has been introducing and improving for chromosomal analysis as an accurate, high resolution and throughput method. In this study we aimed to compare the consistency between conventional G-banding and NGS-based chromosomal copy number analysis for chorionic villus from spontaneous abortion. In addition, the frequency of each chromosomal aneuploidy was evaluated. Materials and methods From February, 2018, to April, 2018, chromosomal analysis for 7 chorionic villus samples from spontaneous abortions (from 7 to 9 weeks) were carried out both conventional G-banding and NGS (VeriSeq-PGS, Illumia). The frequency of each chromosomal aneuploidy was investigated for 110 cases from February, 2018 to December, 2018. Results NGS was able to analyze all 7 cases, but G-banding was able to detect 6 cases, and one case was cell growth failure. In 6 cases analyzed by G-banding, the results of 5 cases were consistent with the results of NGS, but one case suspected maternal cell contamination. Among 7 cases analyzed by the NGS, 2 cases were normal male karyotype (46, XY) and 5 cases were autosomal trisomy, implying that there were no cases suspected of maternal cell contamination. Among 110 cases, chorionic villus was not observed under microscope from 18 samples, NGS result was obtained from 92 cases. Seventy-one cases were found to have abnormal chromosomes (71/92, 77.2%), and 21 cases were normal karyotype (21/92, 22.8%). Aneuploidy of chromosome 22 (21.8%), chromosome 16 (17.9), chromosome 15 (11.9%), chromosome 21 (10.3%) and Chromosome X (10.3%) were more frequently, consistent with previous report. Conclusions Chromosome analysis using NGS not only obtained comparable results to conventional G-banding, but also is able to analyze more accurately and quickly.

Prenatal diagnosis of monochorionic-diamniotic twins discordant for 45,X/46,XX mosaicism

To explore the prenatal screening and diagnosis for a pair of monochorionic-diamniotic (MCDA) twins discordant for 45,X/46,XX mosaicism. Amniotic fluid samples were taken from both twins for whom non-invasive prenatal testing has signaled a high risk for sex chromosomal abnormality. Uncultured amniotic fluid was analyzed by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array). Conventional G-banded karyotyping analysis was performed on the cultured amniotic fluid. Metaphase chromosome analysis showed that one of the twins had a mos 45,X[11]/46,XX[26] karyotype, while the other had a normal karyotype. FISH and SNP-array applied on uncultured amniotic fluid revealed about 30% mosaicism in one of the twins. The twins were confirmed to be monozygotic by SNP-array analysis. To avoid confusion arising from discordant karyotypes in MCDA twins with abnormal non-invasive prenatal testing (NIPT) results, dual amniocentesis should be carried out to obtain amniotic fluid samples for chromosomal as well as molecular analysis. To determine the ratio of 45,X and 46,XX cells in Turner syndrome can provide valuable information for prenatal genetic counseling.

Chromosomal microarray comparative genome hybridization (arrayCGH) in prenatal settings. Proposal for Hungarian application in clinical practice

Invasive prenatal testing and conventional G-banding chromosome analysis have been considered to be the gold standard of fetal cytogenetic diagnosis. Standard karyotyping is, however, constrained by the limits of the resolution of using a microscope. The advantage of molecular karyotyping, array based methods is the evaluation of sub-microscopic copy number changes across the whole genome in a single analysis. The application of array comparative genome hybridization has greatly increased the detection of pathogenic chromosomal abnormalities in prenatal settings. Based on available data in the international literature of the last decade, the clinical utility of arrayCGH is the recognition of some 1-2% and 5-7% additional genetical information compared to metaphase karyotype alone in fetuses without ultrasound anomaly and in fetuses with ultrasonographically detected malformations, respectively. Thus arrayCGH improves the prenatal diagnosis of genetic abnormalities mainly in fetuses with structural sonographic findings. In the present paper we review the literature of chromosomal microarray and make a proposal for the application of the method in Hungarian prenatal genetical practice. Orv Hetil. 2019; 160(13): 484-493.

Recent advances in cytogenetic characterization of multiple myeloma

The detection of cytogenetic abnormalities in multiple myeloma (MM) has received more importance over last years for risk stratification and the new risk-adapted treatment strategies. Conventional G-banding analysis should be included in a routine procedure for the initial diagnostic workup for patients suspected of MM. However, the detection of chromosomal abnormalities in MM by conventional cytogenetics is limited owing to the low proliferative activity of malignant plasma cells as well as the low number of plasma cells in bone marrow specimens. Fluorescence in situ hybridization (FISH) or microarray-based technologies can overcome some of those drawbacks and detect specific target arrangements as well as chromosomal copy number changes. In this review, we will discuss different cytogenetic approaches and compare their strength and weakness to provide genetic information for risk stratification and prediction of outcome in MM patients.

Increased first-trimester nuchal translucency associated with a dicentric chromosome and 9q34.3 microdeletion syndrome

We present prenatal diagnosis and chromosomal microarray analysis (CMA) of 9q34.3 microdeletion in a foetus with an increased nuchal translucency (NT). Conventional G-banding analysis showed a de novo translocation: 45, XX, dic (9;13)(q34;p13). CMA revealed a 3.6 Mb 9q34.3 microdeletion encompassing an OMIM gene of EHMT1 consistent with the diagnosis of Kleefstra syndrome and 9q subtelomeric deletion syndrome. We suggest an application of CMA at prenatal diagnosis in pregnancies with increased NT and an apparent balanced translocation on conventional karyotype.

Cytogenetic evaluation of mesenchymal stem/stromal cells from patients with myelodysplastic syndromes at different time-points during ex vivo expansion

Mounting evidence suggests that in myelodysplastic syndromes (MDSs) bone marrow (BM) mesenchymal stem/stromal cells (MSCs) possess abnormal characteristics and are actively involved in disease pathogenesis. Nevertheless, it is controversial whether these cells harbor clonal cytogenetic aberrations. To probe more deeply into this issue, in the present study we used conventional G-banding and FISH analysis to assess the clonal chromosomal abnormalities of hematopoietic cells (HCs) and cultured MSCs, from 29 MDS patients and 25 healthy individuals, at early, intermediate and late passage. Variable clonal cytogenetic aberrations were detected in HCs from 31% and in MSCs from 34% of MDS patients. Clonal chromosomal abnormalities in MSCs were detected even in patients without aberrations in HCs. They were mostly numerical and always differed from those in HCs from the same individual. Clonal chromosomal abnormalities did not seem to confer a proliferative and/or survival advantage to MSCs. HCs from normal donors harbored no cytogenetic abnormalities, whereas trisomy of chromosome 5 was detected in MSCs from 16% of healthy individuals, in line with other studies. Our results suggest that MDS-derived BM-MSCs are genetically unstable. The significance of this observation in the biology of MSCs and MDS pathogenesis is still unknown and warrants further evaluation.

Analysis of chromosome 22q11 copy number variations by multiplex ligation-dependent probe amplification for prenatal diagnosis of congenital heart defect.

BackgroundCongenital heart defects (CHD) represent one of the most common birth defects. This study aimed to evaluate the value of multiplex ligation-dependent probe amplification (MLPA) as a tool to detect the copy number variations (CNVs) of 22q11 in fetuses with CHD.ResultsA large cohort of 225 fetuses with CHD was screened by fetal echocardiography. Once common chromosome abnormalities in 30 fetuses were screened out by conventional G-banding analysis, the CNVs of chromosome 22q11 in the remaining 195 fetuses were determined by MLPA for prenatal genetic counseling. In 195 CHD fetuses with normal karyotype, 11 cases had pathological CNVs, including 22q11.2 deletion (seven cases), the deletion of 22q11 cat eye syndrome (CES) region (one case), 22q11.2 duplication (one case), 22q13.3 deletion (one case) and 17p13.3 deletion (one case). In total, our findings from MLPA screening represented 4.9 % in our cohort. Among these, three cases were inherited CNVs, and eight cases were de novo. These CNVs were further verified by single nucleotide polymorphism (SNP)-array analysis, and their chromosomal location was refined.ConclusionThis study indicated that MLPA could serve as an effective test for routine prenatal diagnosis of 22q11 in fetuses with CHD.

Emerging technologies in paediatric leukaemia.

Genetic changes, in particular chromosomal aberrations, are a hallmark of acute lymphoblastic lymphoma (ALL) and accurate detection of them is important in ensuring assignment to the appropriate drug protocol. Our ability to detect these genetic changes has been somewhat limited in the past due to the necessity to analyse mitotically active cells by conventional G-banded metaphase analysis and by mutational analysis of individual genes. Advances in technology include high resolution, microarray-based techniques that permit examination of the whole genome. Here we will review the current available methodology and discuss how the technology is being integrated into the diagnostic setting.

Genetic analysis of a family with super-male syndrome

To identify the genetic cause for a family featuring language retardation using combined cytogenetic and molecular genetic methods. Following conventional G-banded karyotype analysis, the additional Y chromosome was identified by fluorescence in situ hybridization (FISH) and multiplex ligation dependent probe amplification (MLPA). Whole genome array comparative genomic hybridization (aCGH) was also carried out to detect minor structural chromosomal abnormalities. The proband's karyotype was determined as 47,XY,+?, and the unknown aberrant chromosome was identified as Yqh+ with FISH, MLPA and aCGH. No other chromosomal abnormality was found in the pedigree. Cytogenetic methods combined with FISH, MLPA, and aCGH can efficiently identify the origin of unknown chromosomes and provide accurate clues for clinical diagnosis and treatment.

Detection and Inheritance Pattern of Copy Number Variations (CNVs) in Children with Multiple Congenital Anomalies

Microscopically visible chromosomal alterations or segmental aneusomy are one of the major causes for congenital anomalies and require cytogenetic investigations. Conventional G-banding analysis is limited to the detection of imbalances greater than 5-10 Mb. Expressivity of a phenotype generally correlates with the degree of genetic imbalance, therefore, patients with a greater genetic imbalance are more likely to be investigated, which creates a diagnostic bias. This does not reflect the full range of phenotypic presentation that may be associated with an imbalance of a particular chromosomal segment. Systematic clinical diagnosis of a rare syndrome can be carried out using FISH to characterize known deletion/duplication breakpoints or by screening for known micro-deletion syndromes and sub-telomeric imbalances where routine banding technique suggests “normal” karyotype. In the past decade, array- Comparative Genomic Hybridization (a-CGH) has made it feasible to detect cryptic imbalances in more number of cases with apparently normal chromosomal makeup in addition to characterize structurally rearranged chromosome. The study of inheritance pattern by a combination of conventional cytogenetic and a-CGH techniques has helped to determine the imbalance as either de novo or inherited. a-CGH could also provide information on whether an imbalance is pathogenic or polymorphic, which could aid in calculating the recurrent risk for future pregnancies. It provides several advantages over conventional cytogenetic techniques such as whole genome coverage in a single experiment with resolution of 20-150 kb, faster turnaround time, higher sensitivity and specificity and non-requirement of dividing cells. Having an extensive coverage of the genome and high resolution, this technique has been pinned as the “first line genetic test” to study cryptic genetic imbalances in cases with developmental delay and congenital anomalies, where G-banded karyotype is “normal”.

A Translocation (9;22)(p24;q11.2) In a Patient With CML

IntroductionIn January 2013 was received in our lab service a bone marrow sample for cytogenetic analysis. The 61 years old female patient presents an elevated white blood cell count (118,000 x10³/mm³) and clinical diagnosis as Chronic Myeloid Leukemia (CML). According the medical information the treatment began with hydroxyurea 3g daily and allopurinol 300mg daily. MethodsWe proceeded with cytogenetic examination of the patient's bone marrow aspirate by conventional G-banding analysis performed on unstimulated short-term cultures (24 hrs). FISH for BCR/ABL translocation was tested using a dual fusion dual color probe. Because of the sample stability we were unable to performed RT-PCR test. ResultsChromosome analysis showed the translocation (9;22)(p24;q11.2) as a sole abnormality in 100% (20/20) of analyzed metaphases. Chronic myeloid leukemia presents as a specific chromosomal abnormality the Philadelphia chromosome, t(9;22)(q34;q11) which is different from the results obtained where the region of translocation of chromosome 9 was p24 instead of the classic q34. This result suggests it is BCR/JACK2 translocation. The FISH analysis showed the presence of a complex Ph chromosome: ABL con BCRx1 (one fusion) and BCRx2;ABLx2. ConclusionThe patient took imatinib without answer. She is still in clinical monitoring with persistent hyperleucocytosis and the treatment is following with hydroxyurea 500mg daily and Interferon 5000 UI three times a week. Further molecular and cytogenetic tests will be performed in a second sample to contribute with evaluation of disease progression and monitoring treatment response. Disclosures:No relevant conflicts of interest to declare.

Chromosome rearrangements in sublines of human embryonic stem cell lines hESM01 and hESM03

Due to possible proliferative effects of karyotypic reorganization of human embryonic stem cell (hESC) lines detailed genetic analysis are indicated prior to any application of hESCs. Molecular cytogenetic analysis of two different hESC sublines was performed and revealed aberrant chromosomes in both of them, i.e. in hESM01r18 (46,ХХ,-18,+mar) and hESM0309 (46,ХХ,del(4),dup(9)). This study shows that microdissection and multicolor fluorescence <em>in situ</em> hybridization (mFISH) can be used to detect the chromosomal changes precisely of the derivative chromosomes that are difficult to identify by conventional G-banded chromosome analysis. In the present study chromosome microdissection and reverse FISH were applied using multicolor fluorescence <em>in situ</em> hybridization (mFISH) for detailed characterization of the derivative chromosomes. The karyotypes of hESC lines were described as: 46,ХХ,r(18)(::p11.31→q21.2::q21.2→p11.31::) and 46,XX,del(4)(q25q31.1),dup(9)(q12q33), respectively. The potential role of the chromosomal regions involved in rearrangements for cell proliferation is discussed.

A 0.7 Mb de novo duplication at 7q21.3 including the genes DLX5 and DLX6 in a patient with split‐hand/split‐foot malformation

Split-hand/split-foot malformation (SHFM1) has been reported to be caused by deletions, duplications or rearrangements involving the 7q21.3 region harboring DSS1, DLX5, and DLX6. We report on a female patient with unilateral syndactyly of the third and fourth fingers of the right hand and overgrowth and lateral deviation of the right great toe. There was a split foot malformation on the right, with absent fifth toe. The left hand was apparently normal and left foot was intact. The patient has no hearing loss. We performed conventional G-banding karyotype analysis, array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH). G-banding karyotype result was normal 46,XX. However, a duplication of 719 kb (96,303,736-97,022,335; NCBI build36/hg18, March 2006) was identified at the 7q21.3 region by aCGH. The array result was also confirmed by FISH analysis. The duplicated region harbors only DLX5 and DLX6, which are known for their role in SHFM1. Additionally, FISH analysis of parental samples showed de novo origin of this abnormality in the patient. This is the first report that highlights the duplication of 719 kb at 7q21.3, harboring only DLX5 and DLX6 associated with the SHFM1 phenotype.

Risk evaluation and preimplantation genetic diagnosis in an infertile man with an unbalanced translocation t(10;15) resulting in a healthy baby

Balanced chromosome structural rearrangement, including reciprocal translocation, Robertsonian translocation and inversion, is an important cause of male infertility that results in azoospermia, oligozoospermia or asthenozoospermia [1]. Unbalanced translocation between two autosomes, which usually results in mental retardation or multiple congenital anomalies, is rare in infertile patients. To our knowledge, only the t(15;18) unbalanced translocation has been reported, in two healthy infertile brothers. Although fluorescence in situ hybridization (FISH) analysis showed that chromosomal normal sperms existed in their semen, these two brothers and their partners chose donor insemination rather than preimplantation genetic diagnosis (PGD) [2]. Whether patients with this kind of rare karyotype could deliver a healthy baby is unclear. Here, we report a man with severe oligoasthenoteratozoospermia carrying a derivative chromosome 10 resulting from the rare unbalanced translocation t(10;15). Based on risk evaluation by sperm FISH, we performed PGD for the couple and successfully established a normal pregnancy. Our results show that patients with such an abnormal karyotype can produce their own offspring, and emphasize the importance of risk evaluation using sperm FISH for infertile male patients. Patient data A couple presented to our reproduction center due to primary infertility that had persisted for 5 years. The woman showed no obvious cause of infertility on examinations, which included: (1) clinical findings: physical examination and medical history evaluation,such as menstrual history, obstetrical history, sexual history, family history, personal and lifestyle history; (2) biochemical tests: liver and renal function; blood cholesterol, blood triglycerides and blood glucose; and immunologic function; and (3) hormonal assay: estradiol, testosterone, progesterone, follicle stimulating hormone (FSH), luteinizing hormone, prolactin, 17-hydroxypregnenolone and thyroid stimulating hormone (TSH); (4) other diagnosis test such as hysterosalpingography. Her karyotype was also normal. However, the man was found to have severe oligoasthenoteratozoospermia after three routine sperm analyses and one sperm morphology examination following the WHO guidelines (Table 1). Conventional G-banding (G-bands after trypsin and Giemsa, GTG) analysis showed that he had only 45 chromosomes, with one derivative chromosome comprising chromosomes 10 and 15 (Fig. 1). Table 1 Semen analysis Fig. 1 a Partial karyotype of the patient showing normal chromosome 10,15 and der(10). b ideogram of the normal chromosome 10,15 and rearranged chromosome. Red, green and aqua bands show the position and color of the FISH probes used for preimplantation genetic ... The couple then accepted a genetic counseling and asked for further fertility evaluation. Oligoasthenoteratozoospermia might have been the cause of the primary infertility in this couple. The husband carried a rare unbalanced translocation comprising chromosome 10 and chromosome 15 that had not been reported previously. The genetic risk was unclear for this kind of abnormal karyotype. His chromosomal structure was similar to that of a Robertsonian translocation; therefore, the meiosis pattern might also be similar to a Robertsonian translocation. Sperm chromosome constitution can be obtained by sperm FISH analysis and might predict the probability of producing an embryo with normal karyotype. If chromosomally normal sperms are present in semen at a high prevalence, PGD can be performed to select embryos with balanced chromosomes for transfer and deliver a healthy baby. This study was approved by the Institutional Review Board of Central South University and Reproductive and Genetics Hospital of Citic-Xiangya, and the patients’ written informed consent was obtained.

Cytogenetic analysis of a complex chromosomal imbalance 14q+ in a fetus featuring multiple congenital defects

To analyze chromosomal imbalance in a fetus presenting with congenital heart disease and mild lateral ventriculomegaly, and to investigate the correlation between genotype and phenotype. The etiology of the fetal congenital diseases was determined, and the feasibility of array-based comparative genomic hybridization (array-CGH) application in molecular cytogenetic diagnosis was evaluated. Following conventional G-banding analysis, array-based comparative genomic hybridization (array-CGH) was applied to delineate the precise location and size of genomic imbalance. A de novo 46, XY, -14, +der14(q31)? karyotype was identified in the fetus by G-banding analysis. Array-CGH has verified the chromosomal imbalance to be 46, XY, -14, +der(12; 14) (p13; q32.33)del(14) (q32.33→ qter). del(14)(q32.33→ qter) is probably the predominant cause of the fetal congenital disease. For its high resolution and accuracy, array-CGH has provided a powerful tool for prenatal diagnosis and genetic counseling.