Progress on genome-wide association studies on mosaic chromosomal alterations / 中华流行病学杂志

Mosaic chromosomal alteration (mCA) is referred to as large-scale somatic mutations on chromosomes, which results in diverse karyotypes in body. The mCA is regarded as one of the phenotypes of aging. Studies have revealed its associations with many chronic diseases such as hematopoietic cancers and cardiovascular diseases, but its genetic basis (e.g. genetic susceptibility variants) is still under-investigated. This paper reviews GWAS studies for mCA on autosomal chromosomes and sex chromosomes [mosaic loss of the Y chromosome (mLOY) and mosaic loss of the X chromosome (mLOX)] based on large population, respectively. Most of the genetic susceptibility loci found in studies for autosomal mCA were associated with copy-neutral loss of heterozygosity. The study of sex chromosome mCA focused on mosaic loss mutations. The number of genetic susceptibility loci for mLOY was high (up to 156), but it was relatively less for mLOX.

Prenatal diagnosis and genetic analysis of a fetus with partial deletion of Yq and mosaicism of 45,X / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnosis and genetic analysis for a fetus with disorders of sex development (DSDs).@*METHODS@#A fetus with DSDs who was identified at the Shenzhen People's Hospital in September 2021 was selected as the study subject. Combined molecular genetic techniques including quantitative fluorescence PCR (QF-PCR), multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis (CMA), quantitative real-time PCR (qPCR), as well as cytogenetic techniques such as karyotyping analysis and fluorescence in situ hybridization (FISH) were applied. Ultrasonography was used to observe the phenotype of sex development.@*RESULTS@#Molecular genetic testing suggested that the fetus had mosaicism of Yq11.222qter deletion and X monosomy. Combined with the result of cytogenetic testing, its karyotype was determined as mos 45,X[34]/46,X,del(Y)(q11.222)[61]/47,X,del(Y)(q11.222),del(Y)(q11.222)[5]. Ultrasound examination suggested hypospadia, which was confirmed after elective abortion. Combined the results of genetic testing and phenotypic analysis, the fetus was ultimately diagnosed with DSDs.@*CONCLUSION@#This study has applied a variety of genetic techniques and ultrasonography to diagnose a fetus with DSDs with a complex karyotype.

Genetic analysis of a child with Pitt-Hopkins syndrome due to a novel variant of TCF4 gene derived from low percentage maternal mosaicism / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a child with Pitt-Hopkins syndrome.@*METHODS@#A child who had presented at the Medical Genetics Center of Gansu Provincial Maternal and Child Health Care Hospital on February 24, 2021 and his parents were selected as the study subjects. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. Karyotype analysis was also carried out for the child, and her mother was subjected to ultra-deep sequencing and prenatal diagnosis upon her subsequent pregnancy.@*RESULTS@#The clinical manifestations of the proband included facial dysmorphism, Simian crease, and mental retardation. Genetic testing revealed that he has carried a heterozygous c.1762C>T (p.Arg588Cys) variant of the TCF4 gene, for which both parents had a wild-type. The variant was unreported previously and was rated as likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Ultra-deep sequencing indicated that the variant has a proportion of 2.63% in the mother, suggesting the presence of low percentage mosaicism. Prenatal diagnosis of amniotic fluid sample suggested that the fetus did not carry the same variant.@*CONCLUSION@#The heterozygous c.1762C>T variant of the TCF4 gene probably underlay the disease in this child and has derived from the low percentage mosaicism in his mother.

Progress of research on chromosomal mosaicism embryos / 中华医学遗传学杂志

Chromosomal mosaicism (CM) is a common phenomenon in preimplantation genetic testing (PGT). In embryos with CM, genetic contents of trophoblastic ectodermal (TE) cells may be different from that of the inner cell mass (ICM) which will develop into the fetus. Embryos with low mosaic proportion could give rise to healthy live births after transplantation, but are accompanied with high pregnancy risks such as high abortion rate. In order to provide a more comprehensive understanding for CM embryos, this article has systematically summarized the recent progress of research on the definition, mechanism, classification, PGT techniques, self-correction mechanism, transplantation outcome and treatment principles for CM embryos.

The value of chromosomal microarray analysis and fluorescence in situ hybridization for the prenatal diagnosis of chromosomal mosaicisms / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the prenatal diagnosis of chromosomal mosaicisms.@*METHODS@#A total of 775 pregnant women who had visited the Prenatal Diagnosis Center of Yancheng Maternal and Child Health Care Hospital from January 2018 to December 2020 were selected as study subjects. Chromosome karyotyping analysis and CMA were carried out for all women, and FISH was used to validate the suspected mosaicism cases.@*RESULTS@#Among the 775 amniotic fluid samples, karyotyping has identified 13 mosaicism cases, which yielded a detection rate of 1.55%. Respectively, there were 4, 3, 4 and 2 cases for sex chromosome number mosaicisms, abnormal sex chromosome structure mosaicisms, abnormal autosomal number mosaicisms and abnormal autosomal structure mosaicisms. CMA has only detected only 6 of the 13 cases. Among 3 cases verified by FISH, 2 cases were consistent with the karyotyping and CMA results, and clearly showed low proportion mosaicism, and 1 case was consistent with the result of karyotyping but with a normal result by CMA. Eight pregnant women had chosen to terminate the pregnancy (5 with sex chromosome mosaicisms and 3 with autosomal mosaicisms).@*CONCLUSION@#For fetuses suspected for chromosomal mosaicisms, CMA, FISH and G-banding karyotyping should be combined to determine the type and proportion of mosaicisms more precisely in order to provide more information for genetic counseling.

Genetic analysis of a fetus with mosaic trisomy 12 and severe heart defects and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with severe heart defect and mosaic trisomy 12, and the correlation between chromosomal abnormalities and clinical manifestations and pregnancy outcome.@*METHODS@#A 33-year-old pregnant woman who presented at Lianyungang Maternal and Child Health Care Hospital on May 17, 2021 due to abnormal fetal heart development revealed by ultrasonography was selected as the study subject. Clinical data of the fetus were collected. Amniotic fluid sample of the pregnant women was collected and subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). The CNKI, WanFang and PubMed databases were searched with key words, with the retrieval period set as from June 1, 1992 to June 1, 2022.@*RESULTS@#For the 33-year-old pregnant woman, ultrasonography at 22+6 gestational weeks had revealed abnormal fetal heart development and ectopic pulmonary vein drainage. G-banded karyotyping showed that the fetus has a karyotype of mos 47,XX,+12[1]/46,XX[73], with the mosaicism rate being 1.35%. CMA results suggested that about 18% of fetal chromosome 12 was trisomic. A newborn was delivered at 39 weeks of gestation. Follow-up confirmed severe congenital heart disease, small head circumference, low-set ears and auricular deformity. The infant had died 3 months later. The database search has retrieved 9 reports. Literature review suggested that the liveborn infants with mosaic trisomy 12 had diverse clinical manifestations depending on the affected organs, which had included congenital heart disease and/or other organs and facial dysmorphisms, resulting in adverse pregnancy outcomes.@*CONCLUSION@#Trisomy 12 mosaicism is an important factor for severe heart defects. The results of ultrasound examination have important value for evaluating the prognosis of the affected fetuses.

Genetic analysis and reproductive intervention of 7 families with gonadal mosaicism for Duchenne muscular dystrophy / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for 7 families with gonadal mosaicism for Duchenne muscular dystrophy (DMD).@*METHODS@#For the 7 families presented at the CITIC Xiangya Reproductive and Genetic Hospital from September 2014 to March 2022, clinical data were collected. Preimplantation genetic testing for monogenic disorders (PGT-M) was carried out for the mother of the proband from family 6. Peripheral venous blood samples of the probands, their mothers and other patients from the families, amniotic fluid samples from families 1 ~ 4 and biopsied cells of embryos cultured in vitro from family 6 were collected for the extraction of genomic DNA. Multiplex ligation-dependent probe amplification (MLPA) was carried out for the DMD gene, and short tandem repeat (STR)/single nucleotide polymorphism (SNP)-based haplotypes were constructed for the probands, other patients, fetuses and embryos.@*RESULTS@#The results of MLPA showed that the probands and the fetuses/probands' brothers in families 1 ~ 4, 5, 7 had carried the same DMD gene variants, whilst the probands' mothers were all normal. The proband in family 6 carried the same DMD gene variant with only 1 embryo (9 in total) cultured in vitro, and the DMD gene of the proband's mother and the fetus obtained through the PGT-M were normal. STR-based haplotype analysis showed that the probands and the fetuses/probands' brothers in families 1 ~ 3 and 5 have inherited the same maternal X chromosome. SNP-based haplotype analysis showed that the proband from family 6 has inherited the same maternal X chromosome with only 1 embryo (9 in total) cultured in vitro. The fetuses in families 1 and 6 (via PGT-M) were both confirmed to be healthy by follow up, whilst the mothers from families 2 and 3 had chosen induced labor.@*CONCLUSION@#Haplotype analysis based on STR/SNP is an effective method for judging gonad mosaicism. Gonad mosaicisms should be suspected for women who have given births to children with DMD gene variants but with a normal peripheral blood genotype. Prenatal diagnosis and reproductive intervention may be adapted to reduce the births of further affected children in such families.

Genetic features of a case with mosaic ring chromosome 4 and a review of the literature / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis, clinical phenotype and pathogenesis for a child with mosaicism ring chromosome 4.@*METHODS@#Clinical data of the child was collected. Peripheral blood chromosomal karyotype G banding analysis, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH) were carried out for the child, in addition with a review of the literature.@*RESULTS@#The child was born full-term with low birth weight, facial dysmorphism, patent ductus arteriosus and ventricular septal defect. His karyotype was determined as mos46,XY,r(4)(p16.3q35.2)[259]/45,XY,-4[25]/47,XY,r(4)(p16.3q35.2), +r(4)(p16.3q35.2)[8]/46,XY,der(4)del(4)(p16.3)inv(4)(p16.3q31.1)[6]/46,XY,dic?r(4;4)(p16.3q35.2;p16.3q35.2)[4]/48,XY,r(4)(p16.3q35.2),+r(4)(p16.3q35.2)×2[3]/46,XY,r(4)(p1?q2?)[2]; CMA result was arr[GRCH37]4p16.3(68 345-2 981 614)×1; FISH result was 45,XY,-4[12]/45,XY,-4×2,+mar1.ish r1(4)(WHS-,D4Z1+)[1]/ 46,XY,-4,+mar1.ishr1(4)(WHS-,D4Z1+)[73]/46,XY,-4,+mar2.ishr2(4)(WHS-,D4Z1++)[1]/47,XY,-4,+mar1×2.ishr1(4) (WHS-, D4Z1+)×2[4]/46,XY,del(4)(p16.3).ish del(4)(p16.3)(WHS-,D4Z1+)[9].@*CONCLUSION@#In this case, the ring chromosome 4 as a de novo variant has produced a number of cell lines during embryonic development and given rise to mosaicism. The clinical phenotype of ring chromosome 4 is variable. The instability of the ring chromosome itself, presence of mosaicism, chromosome breakpoint and range of deletion and/or duplication may all affect the ultimate phenotype.

Comparison of detection rates of chromosome G-banding karyotype analysis and fluorescence in situ hybridization among children with sex chromosome mosaicisms / 中华医学遗传学杂志

OBJECTIVE@#To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms.@*METHODS@#A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared.@*RESULTS@#The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05).@*CONCLUSION@#No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.

A case of a 45,X,46,X+mar male phenotype mosaic Turner syndrome with a mixed gonadal germ cell tumor / Philippine Journal of Obstetrics and Gynecology

@#Turner syndrome is a congenital condition affecting 1 in every 2500 female live births. This condition is characterized by complete or partial loss of the X chromosome. They commonly present with normal female external and internal genitalia and may develop hypogonadism and streak ovaries later in life. We describe an unusual presentation of a case of Turner syndrome – a 31-year-old Filipino with male phenotype mosaic Turner syndrome, with 46,X,+mar[46]/45,X[4] chromosome, presenting with ambiguous genitalia and a pelvoabdominal mass. The patient underwent exploratory laparotomy, peritoneal fluid cytology, adhesiolysis, tumor debulking (gonadectomy) appendectomy, omentectomy, identification and inspection of bilateral ureters and bladder, gonioscopy and biopsy of the urogenital cavity (bladder vs. vagina). Histopathology revealed a mixed gonadal tumor, consisting of 70% yolk sac tumor, and 30% dysgerminoma. The patient eventually succumbed to postoperative complications. Postmortem fluorescence-in situ hybridization revealed a 46,X,+mar[46]/45,X,[4].ish der (Y) (DYZ3+), a marker of chromosome Y origin, consistent with a mosaic type Turner syndrome, associated with increased risk for gonadal malignancy.

Mixed Gonadal Dysgenesis (45 X0/46 XV Mosaicism): A case report

@#Disorders of sexual development (DSD) defined as congenital conditions associated with atypical development of anatomical, gonadal or chromosomal sex, is a rare condition that may present with ambiguous genitalia. Included in the varied classes of DSD is mixed gonadal dysgenesis which is known to be due to mosaicism, a chromosomal aberration. Mosaic individuals may have concerns on growth, hormone balance, gonadal development, sex of rearing and fertility. This case report presents an 18-year old student who presented with primary amenorrhea, delayed secondary sexual characteristics and phenotypic features of Turner syndrome who, on chromosomal analysis revealed 45X0/46XY mosaicism. The patient underwent operative laparoscopy with bilateral gonadectomy on the basis of the increased risk of development of gonadal malignancy in phenotypic females with Y-chromosome material. Histopathological analysis revealed bilateral streak gonads. Hormone replacement therapy was then initiated for the induction of secondary female sex characteristics, as treatment for estrogen deficiency, for the induction of pubertal growth spurt and for optimization of bone mineral accumulation. Management of disorders of sexual development is challenging, thus the need for a multidisciplinary approach involving experts in endocrinology, gynecology, psychology and genetics.

Turner syndrome associated with Down syndrome: about a case / Síndrome Turner asociado a síndrome Down: a propósito de un caso

The coexistence of double aneuploidy of Down and Turner syndromes is rare; most cases have been due to double mitotic errors. The objective of the study was to report a case with monosomy of the X chromosome and trisomy of chromosome 21, in mosaic variety, highlighting the phenotypic effect that the presence of different chromosomal abnormalities can produce and compare with those reported in the literature. A 10-year-old Ecuadorian female, born to a multipregnant mother with 46 years at conception, is seen in consultation with a predominant clinical phenotype of Down syndrome, associated with menarche, presence of pubic and axillary villu, where a karyotype is verified 45 X[7]/47XX+ 21 [3]/46, X, der (X)(: p11.1-> q11.1)[1]/46,XX [1]. The present case is a double Turner-Down aneuploidy, with predominantly X monosomy cell line, who shows important mental retardation and some signs of puberal development not usually in Turner syndrome. These features highlight the clinical importance of doing a karyotype in mental retardation cases and searching low mosaics of another aneuploidies in atypical cases. Its complex chromosomal formula and support with molecular cytogenetics allowed diagnostic confirmation and genetic counseling.

La coexistencia de doble aneuploidía de los síndromes de Down y Turner es rara; la mayoría de los casos se han debido a dobles errores mitóticos. Reportar un caso con trisomía del cromosoma 21 y monosomía del cromosoma en X, en variedad mosaico, que curiosamente presenta un despertar puberal precoz y comparar con los reportados en la literatura. Paciente ecuatoriana de sexo femenino, de 10 años de edad, nacida de madre multigesta con 46 años a la concepción, que es vista en consulta con fenotipo clínico predominante de Síndrome Down, asociado a menarquia y telarquia, donde se constata un cariotipo. El presente caso es el primero informado de mosaicismo de doble aneuploidía de Turner-Down asociado con un despertar puberal precoz. Su fórmula cromosómica compleja y el apoyo con la citogenética molecular permitió la confirmación diagnostica y la asesoría genética.

Genetic testing and analysis of 2 cases of trisomy 11 mosaicism / 南方医科大学学报

Trisomy 11 mosaicism is clinically rare, for which making diagnostic and treatment decisions can be challenging. In this study, we used noninvasive prenatal testing, chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing and fluorescence in situ hybridization for detecting trisomy 11 mosaicism in two cases and provided them with genetic counseling. In one of the cases, the fetus with confined placental mosaicism trisomy 11 presented with severe growth restriction and a placental mosaic level of 44%, and pregnancy was terminated at 25+3 weeks of gestation. In the other case with true low-level fetal mosaicism of trisomy 11, the pregnancy continued after exclusion of the possibility of uniparental disomy and structural abnormalities and careful prenatal counseling. The newborn was followed up for more than one year, and no abnormality was found. Noninvasive prenatal testing is capable of detecting chromosomal mosaicism but may cause missed diagnosis of true fetal mosaicism. For cases with positive noninvasive prenatal testing but a normal karyotype of the fetus, care should be taken in prenatal counseling and pregnancy management.

Whole exome sequencing analysis of a patient with 45,X/46,XY mosaicism and autism spectrum disorder / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing for a patient with 45,X/46,XY mosaicism and autism spectrum disorder (ASD).@*METHODS@#Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter.@*RESULTS@#The proband and his father were found to harbor a heterozygous c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c.268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c.268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance.@*CONCLUSION@#Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.

Genetic analysis of a case with mosaicism of a small supernumerary marker chromosome derived from idic(15) / 中华医学遗传学杂志

OBJECTIVE@#To determine the origin of a mosaicism small supernumerary marker chromosome (sSMC) by cytogenetic and molecular analysis.@*METHODS@#Karyotype analysis, fluorescence in situ hybridization (FISH) and SNP-array were carried out.@*RESULTS@#The karyotype of the patient was mos47,XX,+mar[45]/48,XX,+2mar[3]/46,XX[52]; the SNP-array result was arr[hg19]15q11.1q11.2 (20 161 372-24 314 675)×3, and the repeat fragment was about 4.15 Mb. FISH showed that approximately 50% of the cells have contained a sSMC with double D15Z1 probe site segments derived from abnormal idic(15). This sSMC did not contain SNRPN and PML probe fragments of Prader-Willi syndrome/Angelman syndrome.@*CONCLUSION@#When the patient's karyotype and phenotype are inconsistent, cytogenetic and molecular biology technologies should be combined to clarify the karyotype and gene location, so as to provide more accurate genetic consultation for the follow-up treatments.

Genetic analysis of a fetus with mosaicism of 13q inversion duplication / 中华医学遗传学杂志

OBJECTIVE@#To report on a case of mosaicism 13q inversion duplication, analyze its mechanism, and discuss the correlation between its genotype and phenotype.@*METHODS@#Amniotic fluid and umbilical cord blood were collected at 23 and 32 weeks of gestation, respectively. Combined with G-banding chromosome karyotyping analysis, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) were used to confirm the result.@*RESULTS@#The karyotype of the fetus was determined as 47,XY,+inv dup(13)(q14.3q34)/46,XY. After careful counseling, the couple decided to continue with the pregnancy, and had given birth to a boy at 40 weeks' gestation. Except for a red plaque (hemangioma) on the nose bridge, no obvious abnormality (intelligence to be evaluated) was discovered.@*CONCLUSION@#To provide reference for clinical genetic counseling and risk assessment, the location and proportion of new centromere formation should be fully considered in the case of mosaicism 13q inversion duplication.

Analysis of a patient with tuberous sclerosis complex due to mosaicism TSC2 mutation / 中华医学遗传学杂志

OBJECTIVE@#To analyze variants of TSC1 and TSC2 genes in a Chinese patient with tuberous sclerosis complex (TSC).@*METHODS@#Peripheral blood samples were collected from the patient and her parents with informed consent. Following extraction of genomic DNA, potential variants of the TSC1 and TSC2 genes was detected by using targeted capture next-generation sequencing (NGS) and Sanger sequencing.@*RESULTS@#The patient was found to harbor a de novo mosaicism variant c.3295_3298delG (Val1100CysfsTer3) of the TSC2 gene, with the proportion of the mutant allele determined as 13.4%, which was confirmed by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3295_3298delG (Val1100CysfsTer3) variant was predicted to be pathogenic (PVS1+PS2+PM2).@*CONCLUSION@#The mosaicism heterozygous variant of c.3295_3298delG of the TSC2 gene, as detected by both NGS and Sanger sequencing, probably underlay the TSC2 in this patient.

Searching chromosome mosaicisms in 45, X Turner syndrome: how relevant is it?

ABSTRACT Objective: To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS). Materials and methods: FISH and PCR were performed for the presence of chromosome mosaicism and Y-derived-material and genetic findings were correlated to clinical data. Results: Thirty-one participants were enrolled: 18 (58%) had chromosome mosaicisms (FISH), Y-derived material was found in 2. Yet, SRY primer was found with PCR in only one of them and DYZ3 was not found. The most frequent clinical findings were short or webbed neck (81,82%), high-arched palate (78%), breast hypertelorism, e cubitus valgus and genu valgus (57.6%, both), short fourth metacarpals (46.9%), epicanthic folds (43.8%), shield chest (43.8%), lymphedema (37.5%), and low set ears (34.4%). Both patients with Y-derived-material had primary amenorrhea, dyslipidemia and reached the height of 150 cm despite not treated with recombinant growth hormone (GHr). One of them showed 26% of leukocytes with Y-derived material and few clinical findings. Conclusions: FISH techniques proved efficient in detecting chromosome mosaicisms and Y-derived material and searching in different tissues such as mouth cells is critical due to the possibility of tissue-specific mosaicism. Phenotypical variance in TS may be a signal of chromosome mosaicisms, especially with the presence of Y-derived material.

Prenatal cytogenetic and molecular genetic analysis of a fetus with confined placenta mosaicism for trisomy 16 / 中华医学遗传学杂志

OBJECTIVE@#To review the clinical data of a fetus with false positive result of non-invasive prenatal testing (NIPT) due to confined placental mosaicism (CPM).@*METHODS@#Amniotic fluid sample was taken from a pregnant women with high risk for chromosome 16 aneuploidy for karyotyping analysis, single nucleotide polymorphism array (SNP array) and interphase fluorescence in situ hybridization (FISH). Genetic testing was also conducted on the fetal and maternal surface of the placenta, root of umbilical cord and fetal skin tissue after induced abortion.@*RESULTS@#Cytogenetic analysis of the amniotic fluid sample yielded a normal karyotype. SNP array revealed mosaicism (20%) of trisomy 16 in the fetus. FISH confirmed the presence of mosaicism (25%) for trisomy 16. After induced labor, all sampled sites of placenta were confirmed to contain trisomy 16 by SNP array, while the analysis of fetal skin tissue yielded a negative result.@*CONCLUSION@#CPM is an important factor for false positive NIPT result. Prenatal identification of CPM and strengthened pregnancy management are important to reduce adverse pregnancy outcomes.

Genetic analysis of a fetus with mosaicism of structural aberration of Y chromosome / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic analysis and parental tracing for a fetus with an inconclusive chromosomal karyotype.@*METHODS@#The fetus and its parents were subjected to combined chromosomal karyotyping, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH) and multiplex PCR testing for Y chromosome microdeletions.@*RESULTS@#The fetus was found to have a karyotype of 45,X[18]/46,X,+mar[72]. CMA revealed that the fetus has carried a 2.6 Mb duplication at Yp11.32p11.31 and a 44.5 Mb deletion at Yq11.21q12. Interphase FISH of amniocytes confirmed the chromosomal mosaicism in the fetus, which has derived from Y chromosome. Multiplex PCR revealed deletion of AZFb and AZFc regions on the Y chromosome. No karyotypic abnormality was found with either parent at 400-band level.@*CONCLUSION@#Combined genetic analysis has delineated the aberrant karyotype in the fetus, which has facilitated prediction of its clinical phenotype and genetic counseling.