产前诊断中羊水细胞染色体嵌合体的发现与处理

目的探讨如何处理羊水细胞培养中出现的嵌合现象。方法收集2007年1月至2011年6月因各种产前诊断指征行羊膜腔穿刺及染色体检查检出为嵌合体病例共27例。统计嵌合体检出率、类型、相应脐带血分析结果,并对所有病例进行出生后随访。结果嵌合体发生率为0．69％。其中,性染色体XX／XY嵌合体11例（占40．74％）;数目异常嵌合体13例（占48．15％）;结构异常3例（占11．11％）。其中14例行脐血染色体检查,确诊为真性嵌合体1例,终止妊娠;未行脐血染色体检查13个病例中,除2例失访外,余均正常分娩,出生随访未见异常。结论产前诊断羊水细胞嵌合体多为假性嵌合体,各种类型的假性嵌合体一般预后均良好。正确处理和判断羊水细胞培养中出现的嵌合现象,对产前诊断和遗传咨询具有重要的意义。     

Mosaic trisomy 17 in amniocytes: phenotypic outcome, tissue distribution, and uniparental disomy studies.

Mosaicism for trisomy 17 in amniocyte cultures is a rare finding, whilst postnatal cases are exceptional. In order to gain insight into the possible effects of the distribution of the trisomic line and of uniparental disomy (UPD) on embryofoetal development, we have performed follow-up clinical, cytogenetic and molecular investigations into three newly detected prenatal cases of trisomy 17 mosaicism identified in cultured amniotic fluid. In the first case, the pregnancy ended normally with the birth of a healthy girl, and analysis of newborn lymphocytes and of multiple extra-embryonic tissues was indicative of confined placental mosaicism. The second case was also associated with a normal pregnancy outcome and postnatal development, and only euploid cells were found in peripheral blood after birth. However, maternal isodisomy 17 consequent to a meiosis II error and loss of a chromosome 17 homologue was detected in peripheral lymphocytes postnatally. In the third case, pathological examination after termination of pregnancy showed growth retardation and minor dysmorphisms, and the trisomic line was detected in foetal skin fibroblasts. In addition, biparental derivation of chromosome 17 was demonstrated in the euploid lineage. These results, together with previously reported data, indicate that true amniotic trisomy 17 mosaicism is more commonly of extra-embryonic origin and associated with normal foetal development. Phenotypic consequences may arise when the trisomic line is present in foetal tissues. Case 2 also represents the first observation of maternal UPD involving chromosome 17; the absence of phenotypic anomalies in the child suggests that chromosome 17 is not likely to be subject to imprinting in maternal gametes.     

Confined placental mosaicism.

In most pregnancies the chromosomal complement detected in the fetus is also present in the placenta. The detection of an identical chromosomal complement in both the fetus and its placenta has always been expected as both develop from the same zygote. However, in approximately 2% of viable pregnancies studied by chorionic villus sampling (CVS) at 9 to 11 weeks of gestation, the cytogenetic abnormality, most often trisomy, is confined to the placenta. This phenomenon is known as confined placental mosaicism (CPM). It was first described by Kalousek and Dill in term placentas of infants born with unexplained intrauterine growth restriction (IUGR). Contrary to generalised mosaicism, which is characterised by the presence of two or more karyotypically different cell lines within both the fetus and its placenta, CPM represents tissue specific chromosomal mosaicism affecting the placenta only. The diagnosis of CPM is most commonly made when, after the diagnosis of chromosomal mosaicism in a CVS sample, the second prenatal testing (amniotic fluid culture or fetal blood culture analysis) shows a normal diploid karyotype.     

限制性胎盘嵌合对无创产前检测的影响及临床分析

目的探讨限制性胎盘嵌合(confined placental mosaicism,CPM)对无创产前检测(non-invasive prenatal testing,NIPT)以及妊娠结局的影响。方法应用低深度全基因组测序(copy number variation sequencing,CNV-seq)和单核苷酸多态性微阵列技术(single nucleotide polymorphism array,SNP-array)对8例NIPT假阳性病例进行胎盘多个位置的遗传学检测,结合临床资料分析CPM对NIPT以及妊娠结局的影响。结果在8例NIPT假阳性病例中,5例为CPM,分别为9号三体、13三体、21三体、22三体以及X三体CPM;胎盘不同区域的染色体异常比例差异明显(4%~80%)。5例CPM中,2例表现为胎儿生长受限(fetal growth restriction,FGR)合并其他超声异常,1例表现为孤立性FGR,其余2例生长发育正常。结论CPM是NIPT假阳性的重要原因,NIPT对CPM有较高的敏感性;CPM可能与FGR相关。重视CPM对于NIPT检测前后的遗传咨询以及妊娠管理有重要帮助。     

Comparative genomic hybridization: a new approach to screening for intrauterine complete or mosaic aneuploidy

In the practice of clinical genetics chromosomal aneuploidy in both mosaic and nonmosaic forms has long been recognized as a cause of abnormal prenatal and postnatal development. Traditionally, cytogenetic analysis of cultured lymphocytes has been used as a standard test for detection of constitutional aneuploidies. As lymphocytes represent only one lineage, chromosomal mosaicism expressed in other tissues often remains undetected. The purpose of this study was to assess the utilization of molecular cytogenetic analysis for detection of chromosomal aneuploidy in placental tissues. Using placentas from 100 pregnancies with viable nonmalformed livebirths, both trophoblast and chorionic stroma were analyzed using comparative genomic hybridization (CGH). In all cases with an indication of chromosomal imbalance by CGH, fluorescence in situ hybridization (FISH) analysis was performed to confirm the presence of aneuploidy. To differentiate between constitutional aneuploidy and confined placental mosaicism (CPM), amniotic membrane was analyzed by CGH and FISH techniques. Our results demonstrated five placentas with CPM for chromosomes 2, 4, 12, 13, and 18, respectively, and two constitutional nonmosaic aneuploidies (47,XXX and 47,XXY). Molecular cytogenetic studies of human placental tissues enables easy analysis of both embryonic (amnion) and extraembryonic (chorion) cell lineages. Detection at birth of chromosomal defects affecting intrauterine placental and fetal development is important because these chromosomal defects may continue to have an influence on postnatal development.     

Fetoplacental mosaicism: potential implications for false-positive and false-negative noninvasive prenatal screening results

PurposeNoninvasive prenatal screening for fetal aneuploidy analyzes cell-free fetal DNA circulating in the maternal plasma. Because cell-free fetal DNA is mainly of placental trophoblast origin, false-positive and false-negative findings may result from placental mosaicism. The aim of this study was to calculate the potential contribution of placental mosaicism in discordant results of noninvasive prenatal screening.MethodsWe performed a retrospective audit of 52,673 chorionic villus samples in which cytogenetic analysis of the cytotrophoblast (direct) and villus mesenchyme (culture) was performed, which was followed by confirmatory amniocentesis in chorionic villi mosaic cases. Using cases in which cytogenetic discordance between cytotrophoblast and amniotic fluid samples was identified, we calculated the potential contribution of cell line–specific mosaicism to false-positive and false-negative results of noninvasive prenatal screening.ResultsThe false-positive rate, secondary to the presence of abnormal cell line with common trisomies in cytotrophoblast and normal amniotic fluid, ranged from 1/1,065 to 1/3,931 at 10% and 100% mosaicism, respectively; the false-negative rate was calculated from cases of true fetal mosaicism, in which a mosaic cell line was absent in cytotrophoblast and present in the fetus; this occurred in 1/107 cases.ConclusionDespite exciting advances, underlying biologic mechanisms will never allow 100% sensitivity or specificity.     

Parental decisions of prenatally detected sex chromosome abnormality

Because of the widespread use of amniocentesis, the prenatal recognition of sex chromosome abnormality (SCA) has become increasingly common. Recent literature provided an insight into the understanding of the natural history and prognosis for individuals with SCA. Our study was designed to review the parental decision on pregnancy with SCA. Over the last 10 yr, we diagnosed 38 cases (0.50%) with SCA out of 7,498 prenatal cases. We reviewed the records and the results of the pregnancies. We included the cases (n=25) of apparently normal anatomic fetus to analyze the factors influencing parental decision. We excluded 13 cases with obvious anomaly or presumably bad outcome. Fifteen (60%) couples continued their pregnancies and ten (40%) terminated theirs. Nine couples (64%) out of fourteen mosaicism cases continued their pregnancies. All five pregnancies assisted by reproductive technique continued their pregnancies. More pregnancies were continued when counseling was done by an MD geneticist rather than by an obstetrician. A significant trend was observed with a higher rate of pregnancy continuation in recent years. The genetic counseling is important to give appropriate information to the parents. Establishing guidelines and protocols will help both obstetricians and parents to make a decision.     

Prenatal diagnosis of 45,X/46,XY mosaicism with postnatal confirmation in a phenotypically normal male infant

Prenatal detection of chromosome mosaicism has always been a diagnostic dilemma. In 21 reported cases of chromosomal mosaicism in cultured amniotic fluid cells, only two cases had cytogenetic confirmation of the mosaicism. All 21 pregnancies resulted in either phenotypically normal liveborns or grossly normal abortuses. We report a case of XO/XY mosaicism detected prenatally and confirmed postnatally in a grossly normal male infant. The indication for prenatal cytogenetic diagnosis was advanced maternal age (38 years). A diagnosis of XO/XY mosaicism was made from two separate culture flasks of amniotic fluid cells, with 45,X cells predominating (86.4 % ). The Y chromosome was of normal size but carried no fluorescent band. The parents were counseled and were advised that the phenotype of XO/XY mosaicism can range from relative normality to sexual maldevelopment. They decided to continue this pregnancy. The infant was born at term and was a grossly normal male with normal penis and descended, normal-sized testes. Leukocyte culture from the cord blood and a skin fibroblast culture confirmed the mosaicism of XO/XY. The father's Y chromosome was of identical size and carried a small fluorescent band. It appears that an altered Y chromosome may be predisposed to anaphase lag leading to mosaicism.     

Mosaic partial trisomy 17q2.

Examination of an infant born after prenatal diagnosis of mosaic partial trisomy 17q2 showed the unique phenotypic features of this chromosomal abnormality, that is, frontal bossing, large mouth, brachyrhizomelia, and hexadactyly. Amniocentesis was performed because of polyhydramnios and ultrasound diagnosis of fetal craniofacial dysmorphology and rhizomelic shortening of the limbs. Chromosomal mosaicism was restricted to fetal tissue and amniotic fluid cells. The placental chromosomal complement was normal, suggesting that the abnormality developed after differentiation of embryonic and trophoblastic cells. This emphasises the usefulness of cytogenetic evaluation of placental, fetal, and amniotic fluid cells in delineating the pathogenesis of congenital abnormalities.     

Investigation of confined placental mosaicism (CPM) at multiple sites in post-delivery placentas derived through intracytoplasmic sperm injection (ICSI)

Although earlier studies on pregnancies derived through intracytoplasmic sperm injection (ICSI) reported increased non-mosaic aneuploidy among ICSI children, undetected mosaicism, such as confined placental mosaicism (CPM) has not been evaluated. We investigated the incidence of CPM in post-delivery placentas derived from ICSI, evaluated whether CPM was increased and whether it was a contributing factor to negative pregnancy outcome. [Fifty-one post-delivery placentas were collected from patients who underwent ICSI with a normal or negative pregnancy outcome]. Trophoblast and chorionic stroma from three sites were analyzed by comparative genomic hybridization (CGH) and flow cytometry. Detected abnormalities were confirmed by fluorescence in situ hybridization (FISH). The incidence of CPM in the ICSI population was compared to the general population from published data. We detected three cases of CPM in our study. One abnormality was found by CGH analysis; partial trisomy 7q and a partial monosomy Xp limited to the trophoblast at two sites. The abnormality was associated with a child affected by spina bifida. Two cases of mosaic tetraploidy were observed by flow cytometry in pregnancies with a normal outcome. All three abnormalities were confirmed by FISH analysis. The incidence of CPM in the ICSI study population was 5.88% (3/51), which was not statistically different from published reports in the general population (5.88% (42/714), Chi square, P > 0.05). The post-ICSI population was not at risk for CPM in this study.     

Pre- and postnatal findings in trisomy 17 mosaicism

Trisomy 17 mosaicism is one of the rarest autosomal trisomies in humans. Thus far, only 23 cases have been described, most of them detected prenatally. In only five instances has mosaicism been demonstrated in lymphocytes and/or fibroblasts postnatally, and only in these have multiple congenital anomalies (MCA), facial dysmorphisms, and mental retardation been reported. Patients with trisomy 17 mosaicism at amniocentesis and a normal karyotype in blood and fibroblasts (n = 17) were always healthy. Here, we report on pre- and postnatal clinical, cytogenetic, molecular-cytogenetic, and molecular findings in four patients with trisomy 17 mosaicism. The first case was detected in cultured but not in short-term chorionic villi and amniocytes. Due to MCA on prenatal ultrasound examination the pregnancy was terminated. The second patient is a 13-month-old healthy boy, in whom low level trisomy 17 mosaicism was detected in cultured chorionic villi only. The third patient is a 2-year-old girl with growth retardation, developmental delay, MCA, and trisomy 17 mosaicism in amniocytes, fibroblasts, and placenta, but not in blood and buccal smear. The fourth patient is a 9-year-old boy with growth and mental retardation, sensoneurinal hearing loss, and MCA. Cytogenetic analyses showed trisomy 17 mosaicism in amniocytes, skin fibroblasts, and urinary sediment cells, whereas in blood and buccal smear a 46,XY karyotype was found. Molecular investigations in all four cases indicated biparental inheritance of chromosome 17. Formation of trisomy was most likely due to a maternal meiosis I error in Patient 1 and a postzygotic non-disjunction of the paternal chromosome 17 in Patient 4. Cerebellar malformations, reported in two cases from the literature and in two reported here may be a specific feature of trisomy 17 mosaicism. Since the aberration has rarely been reported in lymphocytes, chordocentesis is not indicated in prenatal diagnosis. Prenatal genetic counseling for trisomy 17 mosaicism in chorionic villi or amniocytes should consider that the clinical significance remains uncertain.     

upd(20)mat is a rare cause of the Silver-Russell-syndrome-like phenotype: Two unrelated cases and screening of large cohorts

Silver-Russell syndrome (SRS) is an imprinting disorder characterized by prenatal and postnatal growth retardation, relative macrocephaly, feeding difficulties and body asymmetry. Recently, upd(20)mat has been identified in few patients with SRS-like features, suggestive of a new imprinting disorder characterized by prenatal and postnatal growth failure. Here, we describe two male patients with upd(20) and feeding difficulties, prenatal and postnatal growth retardation and normal cognitive development. During pregnancy, confined placental mosaicism for trisomy 20 was detected in one of the patients but was not investigated further until identification of upd(20)mat in the neonatal period. To evaluate whether upd(20)mat should be part of the first trier genetic diagnostic in patients with growth retardation, we screened a large cohort of patients (n = 673) referred to our laboratories for SRS-testing without detecting any upd(20). Our results, along with the existing evidence, indicate that upd(20)mat is a very rare cause of growth retardation, but should be followed up when confined placental mosaicism for trisomy 20 mosaicism is observed during pregnancy.     

Prenatal diagnosis of chromosome 4 mosaicism: prognostic role of cytogenetic, molecular, and ultrasound/MRI characterization

Trisomy 4 mosaicism is extremely rare: herein we report the cytogenetic and molecular characterization and prenatal US findings of a case diagnosed prenatally. The diagnosis of level III mosaicism was established in cultured amniotic fluid cells (22.5%). At 22 weeks gestation, micrognathia and hypotelorism were suspected at 2-D sonography, and confirmed at 3-D examination. In addition, 2-D US showed cerebellar hypoplasia associated with borderline ventriculomegaly (confirmed at magnetic resonance imaging, MRI), spine deformity (hemivertebra), and a complete atrioventricular septal defect (AVSD). The pregnancy was terminated. Trisomy 4 mosaicism was confirmed in placental and fetal skin cultured cells. The cord blood karyotype was normal. Molecular analysis excluded uniparental disomy of chromosome 4, and indicated that the trisomy 4 was of maternal meiotic origin. In presence of chromosome 4 mosaicism, accurate fetal sonography and echocardiography are mandatory. Low level mosaicism and normal echographic examinations seem to be associated with good prognosis. In postnatal life, chromosome 4 mosaicism should be suspected, and cytogenetic analysis proposed of further tissues (i.e., skin), in presence of craniofacial dysmorphism, cardiac defects, and abnormal hands/feet, even if mental development is appropriate or only slightly impaired.     

Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis

Cytogenetic analysis of reproductive wastage is an important stage in understanding the genetic background of early embryogenesis. The results of conventional cytogenetic studies of spontaneous abortions depend on tissue culturing and are associated with a significant cell culture failure rate. We performed interphase dual-colour FISH analysis to detect chromosomal abnormalities in noncultured cells from two different tissues-cytotrophoblast and extraembryonic mesoderm-of 60 first-trimester spontaneous abortions from which cells had failed to grow in culture. An original algorithm was proposed to optimize the interphase karyotype screening with a panel of centromere-specific DNA probes for all human chromosomes. The overall rate of numerical chromosomal abnormalities in these cells was 53%. Both typical and rare forms of karyotype imbalance were found. The observation of six cases (19%) of monosomy 7, 15, 21 and 22 in mosaic form, with a predominant normal cell line, was the most unexpected finding. Cell lines with monosomies 21 and 22 were found both in cytotrophoblast and mesoderm, while cells with monosomy 7 and 15 were confined to the cytotrophoblast. The tissue-specific compartmentalization of cell lines with autosomal monosomies provides evidence that the aneuploidy of different human chromosomes may arise during different stages of intrauterine development. The effect of aneuploidy on selection may differ, however, depending on the specific chromosome. The abortions also revealed a high frequency of intratissue chromosomal mosaicism (94%), in comparison with that detected by conventional cytogenetic analysis (29%; P<0.001). Confined placental mosaicism was found in 25% of the embryos. The results of molecular cytogenetic analysis of these cell culture failures illustrate that the diversity and phenotypic effects of chromosomal abnormalities during the early stages of human development are underestimated.     

Clinical Practice Guidelines for Prenatal Aneuploidy Screening and Diagnostic Testing from Korean Society of Maternal-Fetal Medicine: (2) Invasive Diagnostic Testing for Fetal Chromosomal Abnormalities

The Korean Society of Maternal Fetal Medicine proposed the first Korean guideline on prenatal aneuploidy screening and diagnostic testing, in April 2019. The clinical practice guideline (CPG) was developed for Korean women using an adaptation process based on good-quality practice guidelines, previously developed in other countries, on prenatal screening and invasive diagnostic testing for fetal chromosome abnormalities. We reviewed current guidelines and developed a Korean CPG on invasive diagnostic testing for fetal chromosome abnormalities according to the adaptation process. Recommendations for selected 11 key questions are: 1) Considering the increased risk of fetal loss in invasive prenatal diagnostic testing for fetal genetic disorders, it is not recommended for all pregnant women aged over 35 years. 2) Because early amniocentesis performed before 14 weeks of pregnancy increases the risk of fetal loss and malformation, chorionic villus sampling (CVS) is recommended for pregnant women who will undergo invasive prenatal diagnostic testing for fetal genetic disorders in the first trimester of pregnancy. However, CVS before 9 weeks of pregnancy also increases the risk of fetal loss and deformity. Thus, CVS is recommended after 9 weeks of pregnancy. 3) Amniocentesis is recommended to distinguish true fetal mosaicism from confined placental mosaicism. 4) Anti-immunoglobulin should be administered within 72 hours after the invasive diagnostic testing. 5) Since there is a high risk of vertical transmission, an invasive prenatal diagnostic testing is recommended according to the clinician''s discretion with consideration of the condition of the pregnant woman. 6) The use of antibiotics is not recommended before or after an invasive diagnostic testing. 7) The chromosomal microarray test as an alternative to the conventional cytogenetic test is not recommended for all pregnant women who will undergo an invasive diagnostic testing. 8) Amniocentesis before 14 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 9) CVS before 9 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 10) Although the risk of fetal loss associated with invasive prenatal diagnostic testing (amniocentesis and CVS) may vary based on the proficiency of the operator, the risk of fetal loss due to invasive prenatal diagnostic testing is higher in twin pregnancies than in singleton pregnancies. 11) When a monochorionic twin is identified in early pregnancy and the growth and structure of both fetuses are consistent, an invasive prenatal diagnostic testing can be performed on one fetus alone. However, an invasive prenatal diagnostic testing is recommended for each fetus in cases of pregnancy conceived via in vitro fertilization, or in cases in which the growth of both fetuses differs, or in those in which at least one fetus has a structural abnormality. The guidelines were established and approved by the Korean Academy of Medical Sciences. This guideline is revised and presented every 5 years.     

产前诊断中羊水嵌合体形成机制的探讨

目的探讨产前诊断中羊水嵌合体形成的机制,便于临床医生在遗传咨询中正确处理羊水培养中出现的嵌合现象。方法 2004年1月至2010年4月对在中山大学附属第一医院胎儿医学中心因各种产前诊断指征就诊的患者行羊膜腔穿刺术取羊水做染色体检查,从中选取羊水染色体为嵌合体的患者穿刺脐血复查染色体,结合两者的结果探讨羊水嵌合体形成机制。结果羊水嵌合体检出33例,其中25例为假嵌合体,8例为真嵌合体,7例真嵌合体羊水结果与脐血结果一致,1例真嵌合体两者结果不一致。结论正确判断羊水培养中出现的真假嵌合体及其风险,对产前诊断和遗传咨询具有重要的意义。     

The effect of genetic counseling on performance of prenatal cytogenetic diagnosis

Currently the number of pregnant women who have indications for, but do not receive, prenatal cytogenetic diagnosis is increasing. The purpose of this study was to review the prenatal cytogenetic services and to analyze the effect of genetic counseling on performance of the prenatal cytogenetic test. From January 1987 to July 1988, there were 2,796 deliveries at Severance Hospital, Yonsei Medical Center, of which 126 patients had indications for prenatal cytogenetic diagnosis. Chromosomal abnormalities were found in 5 patients (1, monosomy X; 1, trisomy 18; and 3, trisomy 21). Four patients were found in the group who had indications for prenatal cytogenetic diagnosis while only one was found in the group who did not (p less than 0.01). The most common indication for prenatal cytogenetic diagnosis was advanced maternal age (59%). The prenatal test rate was highest in patients whose indications were a previous child with chromosomal abnormality (100%) and parental translocation carrier (100%). Most (89%) of the patients were tested by amniocentesis between the 16th and 20th week of gestation. The two most common reasons for patients not receiving a prenatal cytogenetic diagnosis were late registration (41%) and absence of genetic counseling (34%).     

Monosomy 21 in hematologic diseases

Monosomy 21 mosaicism as a sole cytogenetic abnormality is very uncommon, with 47 cases described in the literature. We identified five cases of low-level monosomy 21 mosaicism since 1998, none of which were confirmed by fluorescence in situ hybridization (FISH) analysis or follow-up cytogenetic studies. These five cases, and many of the previously reported cases, probably represent the random appearance of several monosomy 21 cells as artifacts of cell culture or microscope slide preparation. The most convincing reported cases of monosomy 21 mosaicism suggest a rare association of monosomy 21 with acute myelocytic leukemia and chronic lymphocytic leukemia. Future cases suggestive of monosomy 21 mosaicism should be confirmed by analysis of additional metaphase cells and by FISH analysis of interphase cells.     

Positive cell-free fetal DNA testing for trisomy 13 reveals confined placental mosaicism

PurposeWe report on a case in which cell-free fetal DNA was positive for trisomy 13 most likely due to confined placental mosaicism. Cell-free fetal DNA testing analyzes DNA derived from placental trophoblast cells and can lead to incorrect results that are not representative of the fetus.MethodsWe sought to confirm commercial cell-free fetal DNA testing results by chorionic villus sampling and amniocentesis. These results were followed up by postnatal chromosome analysis of cord blood and placental tissue.ResultsFirst-trimester cell-free fetal DNA test results were positive for trisomy 13. Cytogenetic analysis of chorionic villus sampling yielded a mosaic karyotype of 47,XY,+13[10]/46,XY[12]. G-banded analysis of amniotic fluid was normal, 46,XY. Postnatal cytogenetic analysis of cord blood was normal. Karyotyping of tissues from four quadrants of the placenta demonstrated mosaicism for trisomy 13 in two of the quadrants and a normal karyotype in the other two.ConclusionOur case illustrates several important aspects of this new testing methodology: that cell-free fetal DNA may not be representative of the fetal karyotype; that follow-up with diagnostic testing of chorionic villus sampling and/or amniotic fluid for abnormal test results should be performed; and that pretest counseling regarding the full benefits, limitations, and possible testing outcomes of cell-free fetal DNA screening is important.Genet Med15 9, 729–732.     

Sperm chromosome analysis to assess potential germ cell mosaicism

Human sperm chromosome complements were examined to assess the possibility that the conceptions of two children with the same chromosomal defect, del(13)(q22q32), from chromosomally normal parents were the result of a paternal germ cell mosaicism. Analysis of 216 complements, both by quinacrine banding and by measuring the relative length of chromosome 13, showed no unusual subpopulation of 13s; this decreased the likelihood of a paternal origin of the deletion. Sperm chromosomal analysis is a useful adjunct to available techniques in clinical genetics. When counseling cases involving either structural or numerical de novo chromosome abnormality, it is of importance to discuss the possibility of germ cell line mosaicism as well as to offer prenatal diagnosis for subsequent pregnancies.