Clinical manifestations and the prenatal diagnosis of trisomy 7 mosaicism:Two case reports

BACKGROUND The clinical manifestations of trisomy 7 mosaicism are diverse and nonspecific,so prenatal diagnosis is very difficult.CASE SUMMARY Two pregnant women with abnormal prenatal screening results were included.One was a 22-year-old woman(G1P0).At 31st week of gestation,ultrasound revealed that the posterior horn of the left lateral ventricle was 10 mm and the right renal pelvis had a separation of 7 mm.The other pregnant woman was 33 years old(G2P1L1A0),and her fetus was found to have a cardiac malformation at the 24th week of gestation.Copy number variation sequencing,whole-exome sequencing and karyotype analysis were carried out after amniocentesis,and both fetuses were diagnosed with trisomy 7 mosaicism.After parental counseling,one woman continued the pregnancy,and the other woman terminated the pregnancy.CONCLUSION In trisomy 7 mosaicism,the low proportion of trisomy does not lead to abortion,but can result in abnormal fetal development,which can be detected via ultrasound.Therefore,clinicians need to pay more attention to various aspects of fetal growth and development,combining with imaging,cellular,molecular genetics and other methods to perform comprehensive evaluations of fetuses to provide more reliable genetic counseling for pregnant women.

Complete or partial trisomy 3 in gastro-intestinal MALT lymphomas co-occurs with aberrations at 18q21 and correlates with advanced disease stage:A study on 25 cases

Taji et al . have reported in their study on 13 patients with gastric mucosa-associated lymphoid tissue （MALT） lymphomas an aggressive tumor course in trisomy 3 positive cases. The authors analyzed only stage I patients with classical low-grade marginal zone lymphoma of the MALT type and detected the trisomy 3 using an alphasatellite DNA probe directed to the centromere. Their data support the observation that trisomy 3 is the most frequent cytogenetic aberration in MALT lymphomas .

Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy

AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosaassociated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy.METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy,the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissuefluorescence in situ hybridization (FISH), using chromosomespecific α-satellite DNA probes for chromosomes 3,7,12,and 18 and YAC clones for t(11;18)(q21;q21).RESULTS: Seven of the 13 patients had complete regression(CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients.CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.

The development of colon innervation in trisomy 16 mice and Hirschsprung’s disease

AIM To study the colon innervation of trisomy 16 mouse, an animal model for Downs syndrome, and the expression of protein gene product 9.5 (PGP 9.5) in the stenosed segment of colon in Hirschsprungs disease (HD). METHODS Trisomy 16 mouse breeding; cytogenetic analysis of trisomy 16 mice; and PGP 9.5 immunohistochemistry of colons of trisomy 16 mice and HD were carried out. RESULTS Compared with their normal littermates, the nervous system of colon in trisomy 16 mice was abnormally developed. There existed developmental delay of muscular plexuses of colon, no submucosal plexus was found in the colon, and there was 5mm aganglionic bowel aparting from the anus in trisomy 16 mice. The mesentery nerve fibers were as well developed as shown in their normal littermates. Abundant proliferation of PGP 9.5 positive nerve fibers was revealed in the stenosed segment of HD colon. CONCLUSION Trisomy 16 mice could serve as an animal model for Hirschsprung s disease for aganglionic bowel in the distal part of colon. Abundant proliferation of PGP 9.5 positive fibers resulted from extrinsic nerve compensation, since no ganglionic cells were observed in the stenosed segment of the colon in HD. HD has a genetic tendency.

Large-vessel thrombosis in intestinal Behet's disease complicated with myelodysplastic syndrome and trisomy 8

Behet's disease is characterized by recurrent oral ulcers, genital ulcers, uveitis and skin lesions. Myelodysplastic syndrome (MDS) is characterized by problems due to ineffective hematopoiesis. Several studies have identified a relationship between MDS and Behet's disease, especially intestinal Behet's disease. Trisomy 8 seems to play an important role in these disorders as well. The present case was a 24-year-old woman who had a huge tonsil ulcer with initial symptoms of odynophagia and intermittent fever. We also noted folliculitis on her upper back. Five days later, she began to experience diarrhea and abdominal pain. Abdominal computed tomography and subsequent surgery revealed ileum perforation and enterocolitis with multiple ulcers. Later, she was admitted again for a vulvar suppurative ulcer and suspicious Bartholin's cyst infection. The patient's clinical presentations met the criteria for Behet's disease. Six months after the bowel perforation event, we noted the development of pancytopenia in a routine laboratory examination. All the examinations led to the diagnosis of MDS with trisomy 8. The most unusual finding was that multiple large vessel thrombi developed during follow-up. Previous studies have suggested that trisomy 8 in MDS leads to concurrent intestinal Behet's disease. Moreover, the inflammatory and immune genes related to thrombus formation are overexpressed in cases of MDS with trisomy 8. Trisomy 8 must play a role in thrombosis. Further studies are needed to help clarify the pathophysiology and pathogenesis of these disorders.

Immunohistochemical study on gastroenteric nervous system in trisomy 16 mice:an animal model of Down syndrome

AIM To study the development of gastroentericnervous system in trisomy 16 mouse embryos.The gastroenteric nervous system in trisomy 16mice and their normal littermates,serving ascontrols from embryonic days 13 to 18(ED13-18)was identified by using primary antibody againstprotein gene product(PGP)9.5.METHODS Trisomy 16 mouse breeding andtrisomy 16 mouse embryos were identified fromtheir normal littermates by chromosomeexamination;PGP 9.5 immunohistochemicalstainning.CONCLUSION Trisomy 16 mice, as an animal model for Down syndrome, has abnormality not only in several systems and organs but also in gastroenteric innervation. This report describes for the first time that the development of the gastroenteric nervous system was not only delayed but also pathological.

Atypical Chronic Myeloid Leukaemia with Trisomy 13: a Case Report

ATYPICAL chronic myeloid leukaemia （aCML）, which shows both myeloproliferative and mye- Iodysplastic features, is a type of myeloprolif- erative/myelodysplastic disease as defined bythe World Health Organisation （WHO） classification of the myeloid neoplasms. Because of the presence of neutrophilic leukocytosis, aCML may resemble chronic myeIogenous leukemia （CML）. However, in contrast with CML, aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.

Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21

Elizabeth Fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth Fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.

Trisomy 12 in a Case of Multiple Cutaneous Squamous Cell Carcinoma in Association with Chronic Lymphocytic Leukemia

Chronic lymphocytic leukaemia （CLL）, which shares clinical and morphological overlap with small lymphocytic lyjmphoma （SLL）, is a low-grade clonal B-cell lymphoproliferative disorder that accounts for 25% of all cases of leukaemia in Western countries, while it is considered rare in Oriental patients and is thought to constitute only 2% of all leukemias in these patients. CLL is associated with an increased incidence of secondary malignant neoplasms, such as brain tumors, melanomas, and gastrointestinal-tract carcinomas. However, the simulataneous occurrence of CLL and cutaneous squamous cell carcinoma （SCC） is rarely reported. We present here a case of CLL with multiple SCC on the face. Subsequent studies demonstrated the patient to have a trisomy 12 identified in bone marrow specimen.

Trisomy 21 with t(5; 11) Chromosomal Translocation as New Unfavorable Cytogenetic Abnormalities in Pediatric Acute Myeloid Leukemia Type M2: One Case Report of Nine-year Follow-up and Literature Review

We report one case of pediatric acute myeloid leukemia type 2（AML-M2） who presented with karyotypic aberration of trisomy 21 with the t（5;11） chromosomal translocation. The patient achieved complete remission after two cycles of chemotherapy of daunorubicin, cytarabine and etoposide. Then, follow-up cytogenetic analysis from bone marrow cell cultures demonstrated a normal karyotype of 46, XY. After 9 years, the patient relapsed and the karyotypic abnormalities of trisomy 21 with t（5;11） reappeared. It was concluded that trisomy 21 with t（5; 11） is a new unfavorable cytogenetic aberration in AML-M2.

Molecular Genetic Analysis of Partial 9p Trisomy in Two Chinese Families with Mental Retardation and Facial Anomaly

Mental retardation is defined by significant limitations in intellectual function and adaptive behavior that occur before 18 years of age.Many chromosomal diseases come with mental retardation.We reported two Chinese families with partial trisomy 9p and other chromosome partial monosomy,clinical features of mental retardation and mild facial and pinkie anomalies.In the family 1,we showed that the proband carried a trisomy 9p21.3→pter and monosomy 21q22.3→qter by using fluorescence in situ hybridization analysis.Molecular genetic analysis defined the precise breakpoint on chromosome 9p between markers D9S1846 and D9S171,an interval of about 2.9 Mb on 9p21.3,and the breakpoint on chromosome 21q between markers D21S1897 and D21S1446,a region of about 1.5 Mb on 21q22.3.In the family 2,a patient with trisomy 9p21.3→pter and monosomy 5p15.33→pter,and a de novo maternal balanced translocation between chromosomes 5 and 9 was identified in his mother.Cytogenetic and molecular genetic analysis defined the precise breakpoints on chromosome 9p21.3 and chromosome 5p15.33.Further clinical investigation found that any individual had no refractoriness eczema disease except the proband in this family.These results further implicate that trisomy 9p is associated with mental retardation,and that there may be key gene duplication on chromosome 9p21.3→9pter responsible for mental retardation and mild facial anomaly.This result has been applied successfully in prenatal diagnosis of the second family.

A new partial trisomy 12p with artery catheter vagus,congenital cataract,no turbinate and external auditory canal

We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12 （pl2-pter） transmitted from a maternal reciprocal translocation 6;12. Genetic analysis of umbilical cord blood of a 27-year-old woman, gravida 4, para 1 at 35 weeks＇ gestation due to a tricuspid regurgitation and orbital hypertelorism by sonography revealed an unusual karyotype of 46, XY, der （6） t （6;12） （p24;p12） mat. The pregnancy was terminated at 37 gestational weeks. The proband postnatally displayed by dysmorphic features of a round flat face with prominent cheeks and high forehead, hypertelorism, a short nose, a broad and depressed nasal bridge, anteverted nares, a deformed philtrum, an open mouth, thin upper vermilion and broad everted lower lip, low-set ears and aural atresia, broad hands with simian creases, and a short neck. By anatomy, the fetal was found to have right artery catheter vagus, congenital cataract, no turbinate and external auditory canal. Through the karoytpye-phynotpye analysis on the present patient and a review of other reported cases, we believed that the case was the first report, which expanded the database of partial trisomy 12p, and was of benefit for future clinical genetic counseling. At the same time, this study supported the viewpoint that phenotypic variability depends on the type and extent of the associated partial monosomy

Severe inflammatory disorder in trisomy 8 without myelodysplastic syndrome and response to methylprednisolone:A case report

BACKGROUND Patients with trisomy 8 consistently present with myeloid neoplasms and/or auto-inflammatory syndrome.A possible link between myelodysplastic syndromes(MDS)with trisomy 8(+8-MDS)and inflammatory disorders is well recognized,several cases having been reported.However,inflammatory disorders in patients without MDS have been largely overlooked.Generally,Behçet's disease is the most common type in+8-MDS.However,inflammatory disorders with pulmonary involvement are less frequent,and no effective treatment has been established.CASE SUMMARY A 27-year-old man with recurrent fever,fatigue for>2 mo,and unconsciousness for 1 day was admitted to our emergency department with a provisional diagnosis of severe pneumonia.Vancomycin and imipenem were administered and sputum collected for metagenomic next-generation sequencing.Epstein–Barr virus and Mycobacterium kansasii were detected.Additionally,chromosomal analysis showed duplications on chromosome 8.Two days later,repeat metagenomic next-generation sequencing was performed with blood culture.Cordyceps portugal,M.kansasii,and Candida portugal were detected,and duplications on chromosome 8 confirmed.Suspecting hematological disease,we aspirated a bone marrow sample from the iliac spine,examination of which showed evidence of infection.We added fluconazole as further antibiotic therapy.Seven days later,the patient’s condition had not improved,prompting addition of methylprednisolone as an anti-inflammatory agent.Fortunately,this treatment was effective and the patient eventually recovered.CONCLUSION Severe inflammatory disorders with pulmonary involvement can occur in patients with trisomy 8.Methylprednisolone may be an effective treatment.

A Patient with Trisomy 15 and Subglottic Tracheal Granuloma: Anesthetic Management for Emergency Rigid Bronchoscopy

Trisomy 15 is a rare genetic disorder presenting unique anesthetic challenges. This is a case of a patient with Trisomy 15 and unrepaired ventriculo-septal defect presented for emergent removal of a subglottic tracheal granuloma. Developed anesthetic plan allowed the patient to breathe spontaneously with a combination of inhalational and intravenous anesthetics. Our technique offered optimal operating conditions and adequate depth of anesthesia. The important points of the case include an understanding of the physical characteristics of a patient with Trisomy 15 and unrepaired ventriculo-septal defect and an anesthetic plan for emergent removal of an obstructing subglottic granuloma via rigid bronchoscopy.

Ocular Findings in Trisomy 13: Nasolacrimal Duct Stenosis Case Series

Trisomy 13, also known as Patau Syndrome, is a congenital malformation that leads to several ocular anomalies, of which cataracts are the most common, as well as iris and retinal colobomas, persistent hyperplastic primary vitreous, persistent tunica vasculosa lentis, and microphthalmos. While most do not survive beyond the neonatal period, those that do survive past one year of age have an 84% chance of making it to age 5. Therefore, treatments for ocular problems should be used to improve the quality of life if the child can withstand surgery. The literature on this topic has described histopathologic findings in postmortem eyes. This case series supports those observations and presents a new discovery of nasolacrimal duct obstructions or stenosis. Deciding on surgical intervention in cases with Trisomy 13 can be challenging, and a variety of factors must be taken into account before surgery is considered. Treatment of these cases can be difficult, necessitating deliberate consideration and determination on a case-by-case basis;however, this case series gives additional evidence to help guide these decisions. Traditionally, trisomy 13 was regarded as being lethal, multiple organ malformations and severe intellectual disability.

Dynamic Balance in Children With Trisomy 21:A Pilot Study

At age 5,children with trisomy 21 have roughly 2 years of delayed motor development.We aimed to verify if children with trisomy 21(AD)(N=6,7.67±1.51 years)had a similar performance to children with a typical development(TD)(N=37,5.19±0.40 years old),in a playful motor action(to spin on herself until she cannot get more).On average,ADs gave less laps,for less time,spending more time per rotation,but without significant difference.Of the AD,one-third fell and rose to continue to spin;one-third stopped and resumed spinning(with intervals of 2.05±0.86s).Three ADs performed the action counterclockwise and the other three in clockwise direction.The results support the hypothesis that AD can perform the activity of spinning,with DT(significantly)younger,allowing to AD momentary pauses and conditions for their physical security.

Case Report： Description of a Patient with Trisomy 22 in Inbred Line

Long arm trisomy of chromosome 22 or cat eye syndrome （OMIM#115470） is a disease with an enormous variability of clinical features, ranging from minor malformations like hypertelorism, to major ones, as congenital heart and renal disorders, combined with variable growth retardation. The authors report a case of a newborn female with clinical features of cat eye syndrome with trisomy 22 in inbred line, who died 35 days after birth. The clinical features at the time of diagnosis were： left preauricular appendix, low-set ears, hypertelorism, mongoloid palpebral apertures, right-sided microphthalmia, left-sided anophthalmia, cleft lip and palate, short neck, anomalous pulmonary venous return, severe lung hypertension, hyperechogenic little kidneys and clinodactyly of the fifth finger on the left side. Cerebral ultrasound showed dilatation of both lateral ventricles, with a callosum corpus difficult to evaluate. The cytogenetics diagnostic was made from peripheral blood by conventional cytogenetics techniques in two different laboratories, and confirmed by fluorescent in situ hybridization.

Prenatal genetic diagnosis in a fetus with partial trisomy 18q that inherited from his mother's chromosomal rearrangement

Objective:To report the recurrent spontaneous abortion that were caused by the mother's chromosomal rearrangement which was 18 chromosome inversion;and cytogenetic analysis of the fetal amniotic fluid was performed.Methods: Traditional chromosome karyotype and whole-genome sequencing(WGS) was used to process karyotyping and genomic microdeletion and microduplication analysis.Results: the result of fetal amniotic fluid chromosome karyotype is 46,XY,rec(18),dup(18)(q12.3q23);his mother's chromosome karyotype is 46,XX,inv(18)(P11.3q12);and his father's chromosome karyotype is normal.Conclusions:A male newborn with partial trisomy 18q variation was detected in a fetus whose mother with abnormal pregnancy history, that was combined with traditional chromosome karyotype and WGS. The WGS technology has an important clinical value in the prevention of fetal birth defects of abnormal pregnancy history family in prenatal diagnosis.

Trisomy 18: A Difficult Decision for the Family

Trisomy 18 (Edwards Syndrome) was first reported in 1960 by Edward et al. in a newborn with multiple abnormalities, and is a broad clinical presentation involving more than 130 different abnormalities. Most cases die during the embryonic or fetal life. Only 5% - 10% of the live-born cases survive the first year of life. Prenatal diagnosis is possible. However, the prenatal detection compels parents to make a difficult decision. After the birth of the baby, it also places a material and moral burden on both the family and the national economy due to multiple congenital abnormalities and limited lifespan. On the other hand, pediatricians experience difficulties in making a decision on interventions, especially cardiac surgery and resuscitation, due to the comorbid abnormalities in the neonatal intensive care units, in which medical ethics arises for discussion. The current study presents a case diagnosed with trisomy 18 by chromosome analysis, who was found to have multiple abnormalities with ultrasonography (USG) during the prenatal period and born because the patient’s mother, who was advised to have amniocentesis, decided to continue with the pregnancy.

Molecular cytogenetic detection oftrisomy 21 in interphase nuclei andmetaphase chromosomes

Objective To explore the potential application of molecular methodology in the detection of numerical chromosome aberration for clinical diagnosis and prenatal diagnosis of Down’s syndrome Methods The primed in situ labelling (PRINS) procedure was carried out by in situ annealing of specific oligonucleotide primers to chromosome 13, 16, 18, 21, X and Y, respectively, followed by primer elongation by a Taq polymerase in the presence of labelled nucleotides Detection of the labelling sites was performed by immunocytochemistry and conventional fluorescence microscopy Results Under the stringent annealing temperature, chromosomes 13, 16, 18, X and Y were specifically labelled at centromeres and the procedure was carried out successfully on interphase nuclei as well as on metaphase spreads with easily scorable signals In 33 cases of uncultured peripheral blood lymphocytes and 11 cases of uncultured amniocytes tested, two fluorescence signals were shown on more than 87 6% interphase nuclei when chromosomes 13, 16, 18 were investigated Sex chromosomes were correctly detected in the same way Blind tests on peripheral blood lymphocytes from 14 cases of normal individuals and 12 cases of Down’s syndrome patients and on 9 cases of amniocytes showed that when chromosome 21 was detected by PRINS, two fluorescence spots as positive signals were visible on 89 3% normal nuclei and three spots on 88 8% trisomic nuclei The above results were fully compatible with karyotypic analysis Conclusion PRINS provides a rapid and efficient method for the clinical diagnosis or prenatal diagnosis of trisomy