Prenatal Genetic Diagnosis and Origin Analysis of Rare Complete Translocation Trisomy 18 / 中山大学学报(医学科学版)

ObjectiveTo discuss the origin of rare abnormal karyotypes of fetuses with high risk of trisomy 18 revealed by non-invasive prenatal testing （NIPT） and its impact on fertility. MethodsThe cytogenetic and molecular genetic analyses were performed on the abnormal chromosomes of a prenatally diagnosed fetus with rare complete translocation trisomy 18. Using the keywords “translocation trisomy 18” or “trisomy 18 translocation” in both Chinese and English， we searched PubMed， CNKI， SinoMed， WanFang Data， CQ VIP and the Chinese Medicine database. The relevant case series were retrieved and critically appraised. ResultsG-banded karyotype analysis showed that the maternal karyotype was 46，XX，t（9；18）（q31.2；q23） and the fetal karyotype was 47， XN， t （9； 18） （q31.2；q23）mat， +18， which was a rare complete translocation type of trisomy 18. The SNP array revealed the fetus had increased copy number of chromosome 18 and two complete chromosome 18 inherited from the mother with balanced chromosomal translocation. Literature search found two children with complete translocation trisomy 18 reported abroad. Both of them had trisomy 18 phenotype and originated from the balanced translocation between parental chromosome 18 and other chromosomes. ConclusionNIPT gives an effective advance warning of trisomy 18. SNP array not only improves the detection rate of chromosomal abnormalities， but also helps identify the origin. The karyotype is still the gold standard for prenatal diagnosis.

A Rare Case of Acute Lymphoblastic Leukemia with t(12;17)(p13;q21) / 대한진단검사의학회지

Patients with ALL rarely present with t(12;17)(p13;q21) as the primary clonal abnormality; this abnormality is associated with the expression of myeloid antigens. In this study, we have reported presumably the first case of this chromosomal abnormality in Korea, thereby facilitating the delineation of a distinct subtype of ALL. A 57-yr-old woman was referred to our hospital because of pancytopenia. Peripheral blood examination showed 55% blasts. The bone marrow was markedly hypercellular, and about 82.4% of all nucleated cells were blasts. The results of immunophenotyping and cytochemical staining suggested early precursor B-ALL. Cytogenetic analysis of the bone marrow cells showed a complex karyotype, including a reciprocal translocation between the short arm of chromosome 12 and the long arm of chromosome 17, t(12;17)(p13;q21). Data from array comparative genomic hybridization were almost consistent with the cytogenetic findings.

A Case of Partial Trisomy 9 due to Maternal Balanced Translocation t(9;21)(q21.2;q11.2) / 대한주산의학회잡지

Trisomy 9 syndrome was first reported by Retheore in 1970 and has been rarely reported. This syndrome consists of partial and complete trisomy 9. It is characterized by growth and mental retardation, craniofacial abnormalities including microcephaly, hypertelorism, prominent nose, deep-set ears and down-slanting palpebral fissures. Congenital heart diseases and congenital dislocations of knee are also common in trisomy 9 syndrome. Here, we report a very rare case of partial trisomy 9 due to maternal balanced translocation t(9;21). He showed craniofacial abnormalities, brain malformation, cardiac defect, hydronephrosis and congenital dislocations of hip and knee joints.

A Case of Partial Trisomy 9 due to Maternal Balanced Translocation t(9;21)(q21.2;q11.2) / 대한주산의학회잡지

Trisomy 9 syndrome was first reported by Retheore in 1970 and has been rarely reported. This syndrome consists of partial and complete trisomy 9. It is characterized by growth and mental retardation, craniofacial abnormalities including microcephaly, hypertelorism, prominent nose, deep-set ears and down-slanting palpebral fissures. Congenital heart diseases and congenital dislocations of knee are also common in trisomy 9 syndrome. Here, we report a very rare case of partial trisomy 9 due to maternal balanced translocation t(9;21). He showed craniofacial abnormalities, brain malformation, cardiac defect, hydronephrosis and congenital dislocations of hip and knee joints.

The Recurrent Pregnancy Loss Associated with a Female Carrier of a Structural Chromosome Rearrangement

Inversion, one of the balanced rearrangements, usually does not lead to phenotypic abnormalities; all genetic information exists in the proper amount, merely in a different order or in an abnormal location. However, offspring of an inversion carrier is at risk of chromosomal imbalance because an inversion loop can be formed during crossing-over of the paternal and the maternal chromosomes in meiosis. We report a 38-year-old woman with inversion and balanced translocation and her fetus with unusual rearrangement causing chromosomal imbalance. We performed conventional cytogenetic analysis, MLPA, and subtelomeric FISH in the cells of the embryo. The results showed that the distal portion of chromosome 13q was added to the terminal portion of chromosome 9p during crossing-over. Therefore, the final karyotype of the fetus was 46,XY,rec(9)t(9;13)(p22;q32)inv(9)(p12q13)mat, confirmed using molecular-cytogenetic analyzing tools.

A Case of Partial Trisomy 14q derived from Paternal Balanced Translocation / 대한주산의학회잡지

Partial trisomy 14q is an extremely rare disorder. Approximately 50 cases have been reported around the world. This disorder results from a malsegregation or non-disjunction of balanced translocated chromosome, thus the offspring inherits such a chromosome. In this report, the father's chromosomal arrangement was 46, XY, t(11;14)(q25;q32.1) and the mother had a normal chromosomal arrangement. We experienced a case of partial trisomy 14q in a male neonate who had craniofacial abnormalities, frontal bossing, bulgin fontanelle, hypertelorism, low-set ears, wide and flat nasal bridge, thin cupid bow lip and micrognathia. The karyotype of his chromosome was 46,XY,der(11)t(11;14)(q25;q32.1). We report the case with a review of the literature.

A Case with Partial Monosomy 6q and Partial Trisomy 14q Derived from Maternal Balanced Translocation / 대한주산의학회잡지

There are several cases of partial monosomy or partial trisomy derived from maternal balanced translocation, but partial monosomy 6q and partial trisomy 14q derived from maternal balanced translocation has not been reported around the world. The authors experienced a case of partial monosomy 6q and partial trisomy 14q derived from maternal reciprocal balanced translocation t (6;14) in a neonate with multiple anomalies including intrauterine growth retardation, facial and cardiac anomalies. We report the case with a brief review of associaed lieratures.

A Case of Partial Trisomy 9pter --> q13 due to Paternal Balanced Translocation t (9;21) (q13;q21) / 대한진단검사의학회지

Trisomy 9p is one of the most frequent autosomal anomalies compatible with a long survival rate. Clinical characteristics are craniofacial dysmorphisms including hypertelorism, prominent nose, deepset eyes, and down-slanting palpebral fissures. The degree of clinical severity in trisomy 9 roughly correlates with the extent of trisomic chromosomal material. If the trisomic segments include the long arm of chromosome 9, clinical findings may not fit into the trisomy 9p but rather resemble trisomy 9 mosaic syndrome and are associated with muscular and cardiac anomalies. Therefore, breakpoints as well as clinical findings need to be precisely defined for differential diagnosis. Cases with trisomy 9p, especially involving proximal 9q, are very rare in Korea. The patient was a 1,920 g male infant born at 36 weeks 3 days of gestation to a 27-yr-old mother and 32-yr-old father after Cesarian section. The patient showed specific craniofacial anomalies, cardiac defects, and hand anomalies. Routine cytogenetic analysis, performed on peripheral blood using GTG banding, showed 46,XY,+der(9)t (9;21)(q13;q21),-21pat. Furthermore, FISH (Vysis Inc., USA) analysis with whole chromosome painting probes confirmed the derivative chromosome 9.

Dandy-Walker malformations in a case of partial trisomy 9p (p12.1→pter) due to maternal translocation t(9;12)(p12.1;p13.3).

We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12) (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient.

Sprengel's deformity associated with a de novo balanced translocation involving chromosome 3 and 17 / 소아과

This is the first case of a de novo balanced translocation 46, XY, t(3;17)(p12.2;q25) associated with multiple musculoskeletal abnormalities, including Sprengel's deformity (congenital undescended scapula to be reported). This translocation has not been described previously with this congenital anomaly in Korea.

A Case of Partial Monosomy 10q with Partial Trisomy 22q due to Maternal Balanced Translocation

Partial monosomy of chromosome 10q is a rare chromosomal anomaly. Most cases of partial deletion 10q have chromosome breakpoints in the 10q25 or 10q26 region. Recently about 30 cases with breakpoint in the 10q26 region have been reported. Partial trisomy of chromosome 22q is also a rare chromosomal anomaly. Most cases of partial duplication 22q are 22q proximal segment duplications known as Cat-eye syndrome. The other cases, 22q11.2 microduplications and 22q distal long arm (22qter) duplications, are also reported but exceedingly rare. We experienced a male neonate who had facial dysmorphisms, congenital heart defect and cryptorchidism. His chromosomal analysis revealed an deletion of chromosome 10q26.1-->qter and duplication of chromosome 22q11.2-->qter caused by maternal balanced translocation e.g. partial monosomy 10q and partial trisomy 22q. Although some cases of partial monosomy 10q were accompanied by other chromosomal abnormalities, this combination of chromosomal abnormalities has not been reported in the literature.

Clinical and Cytogenetic Analysis of Children with Maternal Chromosomal Balanced Translocation / 소아과

PURPOSE: Parents' genetic information plays an important role in their children's genetic expression. Human chromosome has 23-paternal chromosomes and 23-maternal chromosomes. Parental chromosomal translocation can induce clinical problems in their children because of imbalance in genetic information. We intent to analyze the cytogenentic and clinical features about children with maternal balanced translocation between chromosome 15 and 18. METHODS: We detected by one family's FISH study of chromosome 15. We have evaluated children born to clinically normal parents about peripheral bood analysis, endocrine, metabolic, radiologic study, electroencephalogram and social & intelligence scale. and We analysis their clinical manifestation by hospital records. RESULTS: Patient's father and elder sister are normal clinically and genetically. Her mother's chromosome show balanced translocation, 46, XX, t (15; 18) (p11.2; p11.3). One child has 46, XX, der (18) t (15; 18) (p11.2; p11.3), mental retardation, growth retardation, speech & social developmental delay, recurrent infection and mild mitochondria dysfunction. Her young brother has 46, XY, der (15) t (15; 18) (p11.2; p11.3), mental retardation, aggressive behavior, obesity and speech developmental delay. CONCLUSION: In this study we observed the children with developmental delay, dysmorphic facial features, mental retardation, growth retardation associated with growth hormone deficiency and aggressive behavior due to unbalanced translocation between chromosome 15 and 18.

Recurrent Partial Trisomy 1q in Maternal Balanced Translocation t(1;11)(q32;q23) / 대한산부인과학회잡지

Abnormal offsprings from balanced translocation carriers usually inherit only one of the translocated products and are therefore partially trisomic for one chromosome and partially monosomic for another. Partial trisomy 1q usually demonstrates fetal growth restriction and anomalies of head, face, urogenital tract, heart, finger and toes with a wide range of characteristics and severities. It has been reported in a few individuals in the world and this is the first report of partial trisomy 1q in Korea. We present the case of recurrent partial trisomy 1q in maternal balanced translocation which was prenatally diagnosed by amniocentesis with fluorescence in situ hybridization(FISH) based on abnormal ultrasonographic findings and poor obstetric history.

A Balanced Translocation t (2:18) (p23:q23) in the Family

It has been estimated that chromosomal abnormality occurs in 0.4% of live births. A balanced translocation between chromosome 2 and 18, t (2;18) (p23;q23), is extremely rare. We report a neonate whose karyotype was 46, XY t (2;18) (p23;q23). He had multiple anomalies such as micrognathia, low-set ears, short neck, undescended testes, atrial septal defect, and decreased physical activity. Chromosomal analysis with G banding in high resolution showed a balanced translocation t (2;18) (p23;q23). The same chromosomal abnormality was found on the family for 3 generations.

A Case of Wolf-Hirschhorn Syndrome Resulting from Familial Translocation

Wolf-Hirschhorn syndrome is caused by a partial loss of the distal short arm of chromosome 4. Characteristic clinical features are severe growth retardation, mental retardation, seizures, congenital cardiac defects, urogenital abnormalities, microcephaly, hypertelorism, prominent glabella, cleft lip and palate and micrognathia. In 87% of cases, chromosome 4 deletion arises as a de novo event, whereas in the remaining cases it is derived from a familial balanced translocation. Chromosomal study of the patient showed 46 XX der(4)t(4;18)(p15.2;q23), and the patient's mother was found to have a balanced translocation, 46 XX t(4;18)(p15.2;q23).

The Frequency of Chromosomal Abnormalities and the Prenatal Cytogenetic Analyses for Couples with Recurrent Abortions

Between 1988-1998, cytogenetic analyses were performed for 1,476 couples and 162 women with recurrent abortions. We applied GTG-banding, high resolution-banding and FISH (fluorescent in situ hybridization) techniques in this study. The frequency of balanced translocations was 3.6% (112/3114). Of them, 74 cases (2.38%) were reciprocal translocations and 38 (1.22%) were robertsonian translocations. Chromosome aberrations were more frequent in women (80 cases) than in men (32 cases). No phenotypical abnormalities were found in all carriers who had experienced recurrent spontaneous abortions or experienced giving birth to malformed offsprings. Prenatal cytogenetic analyses were carried out on 40 subsequent pregnancies for carrier couples with balanced translocation. The fetal karyotypes showed that 13 cases (32.5%) were normal, 25 (62.5%) were balanced translocations, and two (6%) were unbalanced translocations. It is believed that the frequency of chromosomal abnormalities in patients with recurrent spontaneous abortion is higher than that of the normal population. Most of the fetal samples showed normal karyotypes or balanced translocations matching that of one of their parents. Although the incidence of chromosomal imbalance in the fetuses was relatively low in prenatal cytogenetic analysis, individuals with balanced translocations are predisposed to giving birth to malformed offsprings with partial trisomy or monosomy. Therefore, we recommend the cytogenetic and the prenatal cytogenetic analysis for those who experiences recurrent abortion as well as in case they become pregnant, to prevent the birth of offsprings with chromosomal abnormalities.

A Case of 3p Partial Trisomy

3p partial trisomy is a rare chromosomal anomaly. We experienced a case of 3p partial trisomy in a male neonate. It was diagnosed by clinical and chromosoaml study. He had multiple anomalies such as brachycephaly, wide open fontanelle, square face, hypertelorism, mongoloid palpebral fissure, micrognathia, low set malformed ear, bilateral cleft lip and palate, double outlet right ventricle, atrial septal defect, ventricular septal defect, left ventricular hypoplasia, renal microcysts and micropenis. He was manifested intrauterine growth retardation. Peripheral blood chromosome studies showed an additional chromosomal material at the distal part of the short arm of chromosome 7. Analysis of chromosomes of family members showed that the father had normal karyotype, but the mother had reciprocal balanced translocation,46, XX, t(3;7)(p25;p22). The karyotype formula of the propositus was thus,46,XY,der(7),t(3;7)(p25;p22)mat, that is unbalanced for a duplication 3p25-->3pter, resulting from segregation of a balanced maternal translocation. Two years after patient's birth, his sister was born at 40 weeks of gestation without congenital anomalies. In the case of his sister, amniocentesis and chromosome studies had been done at 16 weeks of gestation. The result of the chromosome analysis was 46,XX,t(3;7)(p25;p22), as in her mother. We report a neonate with multiple congenital anomalies due to partial trisomy for the short arm of chromosome 3, his mother and a female sibling with t(3;7)(p25-->p22).

A case of 4p- syndrome with oligomeganephronia

No abstract available.