Prenatal diagnosis of mosaic tetrasomy 18p Chen, Chih-Ping; Ko, Tsang-Ming; Su, Yi-Ning ...
Taiwanese journal of obstetrics & gynecology,
12/2012, Letnik:
51, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract Objective To present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from isochromosome 18p, by interphase fluorescence in ...situ hybridization (FISH) on uncultured amniocytes. Case Report A 41-year-old woman underwent amniocentesis at 18 weeks of gestation, because of advanced maternal age. Amniocentesis revealed a de novo supernumerary isochromosome 18p in two of 14 colonies of cultured amniocytes. Repeated amniocentesis was performed at 22 weeks of gestation. Interphase FISH analysis on uncultured amniocytes showed four 18p11.32-specific probe (RP11-324G2) signals in 5.7% (3/53 cells) of uncultured amniocytes. A multiplex ligation-dependent probe amplification P095 test kit and array comparative genomic hybridization analysis did not detect genomic imbalance in chromosome 18. Cytogenetic analysis of cultured amniocytes at repeated amniocentesis revealed a karyotype of 47,XY,+i(18)(p10)3/46,XY23. The pregnancy was carried to 38 weeks of gestation, and a healthy 3120 g male baby was delivered. When examined at 2 months of age, the infant was normal in growth and development, without phenotypic abnormalities. The cord blood had a karyotype of 46,XY. Polymorphic DNA marker analysis excluded uniparental disomy 18. Interphase FISH analysis on uncultured urinary cells showed 9.4% (3/32 cells) mosaicism for tetrasomy 18p. Conclusion There is cytogenetic discrepancy between amniocytes and cord blood lymphocytes in prenatally detected mosaic tetrasomy 18p. Interphase FISH on uncultured amniocytes has the advantage of rapid confirmation of low-level mosaicism for tetrasomy 18p at amniocentesis.
Background: The objectives of the present study were to explore whether maternal psychosocial factors, mental health and work stress around delivery, are related to the behavior of 2‐year‐old ...children.
Methods: In a prospective cohort study design, pregnant women attending the National Taiwan University Hospital for delivery and post‐partum care from April 2004 to January 2005 were recruited and their children were observed at 24 months. A total of 186 mother–term‐born child dyads completed the measurement. The five‐item Mental Health Index (MHI‐5) self‐report data of maternal psychosocial factors were selected from the Taiwanese version of the short form 36 (SF‐36). The Child Behavior Checklist for age 1½–5 (CBCL/1½‐5) was completed by the parents when the child was 2 years old.
Results: The mean score of mental health around delivery was 68.11. The proportion of mothers with work stress seldom and always was 61.8% and 24.7%, respectively. The mean of the total CBCL score, and internalizing, externalizing behavior and sleep problems scores was 45.95, 11.89, 15.59 and 4.23, respectively. After adjusting for the potential confounders, maternal work stress around delivery was found to have a significant effect on the total CBCL and externalizing, attention and aggressive, behavioral problems of 2‐year old children. Maternal mental health around delivery, however, did not show significant effects on child behavior.
Conclusions: Work stress around delivery seems to aggravate children's externalizing behavior problems at 2 years old. It is therefore important to improve the psychosocial health and reduce the stress of pregnant women.
Aim: To explore whether maternal psychosocial factors around delivery are related to development of 2‐year‐old children.
Methods: Pregnant women going to the hospital for delivery were recruited, ...and their children were observed at 24 months. A total of 186 mother–child dyads completed the measurement. Self‐report data of maternal psychosocial factors around delivery were selected from the Taiwanese version of the short‐form 36. The Comprehensive Developmental Inventory for Infants and Toddlers was completed by interviewers and the main care givers for the child at 2 years old.
Results: Using the multiple linear regression analysis and adjusting for potential confounders, maternal vitality around delivery was found to have a significantly positive relationship with the whole Comprehensive Developmental Inventory for Infants and Toddlers (P = 0.005) and self‐help development (P = 0.001), but work stress had a significantly negative relationship with motor development (seldom, P = 0.050; always, P = 0.048).
Conclusions: Maternal vitality around delivery was beneficial to a child's self‐help development, while work stress seemed to be an adverse effect on child's motor development in later life. It is important to improve the psychosocial health of pregnant women.
To examine the role of placenta growth factor (PlGF) in the pathogenesis of pulmonary emphysema, we generated PlGF-transgenic (TG) mice using a phosphoglycerate kinase promoter. This resulted in ...constitutive overexpression of PlGF. In these TG mice, pulmonary emphysema, with enlarged air spaces and enhanced pulmonary compliance, first appeared at 6 months of age and became prominent at 12 months. Increased alveolar septal cell apoptosis was noted in their lungs. Fluorescence-activated cell sorter analysis suggests that these apoptotic septal cells are type II pneumocytes. At the same time, the messenger RNA of vascular endothelial growth factor and platelet-endothelial cell adhesion molecule-1, an endothelial cell marker, were downregulated indicating a reduced number of endothelial cells and its survival factor VEGF. In vitro, exogenous PlGF can inhibit the proliferation and promote the cell death of mouse type II pneumocytes. In normal newborn mice, abundant expression of PlGF messenger RNA was detected in the lungs during saccular division but was rapidly downregulated after alveolarization was complete. Thus, a persistently elevated PlGF was detrimental to the developed lung and causes the emphysematous change seen in our TG mice. Our study suggests that PlGF plays an important role in the pathogenesis of pulmonary emphysema via its action on type II pneumocytes.
Abstract Objective To present prenatal diagnosis of chromosome 1p32-p31 deletion syndrome with NFIA haploinsufficiency, ventriculomegaly, corpus callosum hypogenesis, abnormal external genitalia, and ...intrauterine growth restriction and to review the literature. Materials, Methods, and Results A 26-year-old, primigravid woman was referred for amniocentesis at 30 weeks of gestation because of hydrocephalus and short limbs. Prenatal ultrasound showed macrocephaly, prominent forehead, ventriculomegaly, corpus callosum hypogenesis, micrognathia, and ambiguous external genitalia. Amniocentesis was performed, and array comparative genomic hybridization using uncultured amniocytes revealed a 22.2-Mb deletion of 1p32.3-p31.1 arr cgh 1p32.3p31.1 (55,500,291 bp–77,711,982 bp)×1 encompassing the genes of NFIA , GPR177 , and 89 additional genes. Cytogenetic analysis revealed a karyotype of 46,XX,del(1)(p31.1p32.3)dn. At 33 weeks of gestation, a dead fetus was delivered with a body weight of 1536 g (<5th centile); relative macrocephaly; a broad face; prominent forehead; hypertelorism; anteverted nostrils; micrognathia; low-set ears; and abnormal female external genitalia with labial fusion, labial hypertrophy, absence of vaginal opening, and clitoral hypertrophy. Polymorphic DNA marker analysis determined a paternal origin of the deletion. Conclusion Prenatal diagnosis of ventriculomegaly with an abnormal corpus callosum should alert subtle chromosome aberrations and prompt molecular cytogenetic investigation if necessary. Fetuses with chromosome 1p32-p31 deletion syndrome and haploinsufficiency of the NFIA gene may present ventriculomegaly, corpus callosum hypogenesis, abnormal external genitalia, and intrauterine growth restriction in the third trimester.
Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene have been reported in patients with chronic pancreatitis. The authors examine whether the mutations and haplotypes of CFTR ...will increase the risk of developing idiopathic chronic pancreatitis (ICP) in Chinese and their genotype and phenotype correlations. Seventy‐eight patients with ICP and 200 geographically and ethnically matched controls in Taiwan were analyzed. The entire 27 coding and intronic regions of the CFTR gene were identified using heteroduplex analytical techniques and confirmed by sequencing analysis. The presence of 125G/C, 1001+10C>T, IVSTn(TG)m, 1540A>G, c2694T>G, and c4521G>A were determined by directing sequencing. Abnormal CFTR allele was found to be thrice as frequent in ICP patients as in controls (22/156 vs 19/400, p < 0.0001). T5 allele was associated with early onset of ICP. In six‐loci haplotype analysis, 13 common haplotypes were assembled in the 278 individuals tested. The 125G/1001+11C/TG12/470M/2694T/4521G haplotype was associated with risk of ICP (odds ratio 11.3; 95% confidence interval 2.3–54.6, p = 0.008) in Chinese. The mutation spectrum is different from other ethnic groups. A population‐specific panel of CFTR changes should be recommended for targeted populations including ICP in Chinese. It is important to design suitable screening programs for different populations.
Hemophilia A represents the most common and severe inherited hemorrhagic disorder. It is caused by mutations in the F8 gene, which leads to a deficiency or dysfunctional factor VIII protein, an ...essential cofactor in the factor X activation complex.
We used long-distance polymerase chain reaction and denaturing high performance liquid chromatography for mutation scanning of the F8 gene. We designed the competitive multiplex PCR to identify the carrier with exonal deletions. In order to facilitate throughput and minimize the cost of mutation scanning, we also evaluated a new mutation scanning technique, high resolution melting analysis (HRM), as an alternative screening method.
We presented the results of detailed screening of 122 Taiwanese families with hemophilia A and reported twenty-nine novel mutations. There was one family identified with whole exons deletion, and the carriers were successfully recognized by multiplex PCR. By HRM, the different melting curve patterns were easily identified in 25 out of 28 cases (89%) and 15 out of 15 (100%) carriers. The sensitivity was 93 % (40/43). The overall mutation detection rate of hemophilia A was 100% in this study.
We proposed a diagnostic strategy for hemophilia A genetic diagnosis. We consider HRM as a powerful screening tool that would provide us with a more cost-effective protocol for hemophilia A mutation identification.
Abstract Hemophilia B (HB) is an X-linked recessive disorder characterized by mutations in the clotting factor IX ( FIX ) gene that result in FIX deficiency. Previous studies have shown a wide ...variation of FIX gene mutations in HB. Although the quality of life in HB has greatly improved mainly because of prophylactic replacement therapy with FIX concentrates, there exists a significant burden on affected families and the medical care system. Accurate detection of FIX gene mutations is critical for genetic counseling and disease prevention in HB. In this study, we used denaturing high-performance liquid chromatography (DHPLC), which has proved to be a highly informative and practical means of detecting mutations, for the molecular diagnosis of our patients with HB. Ten Taiwanese families affected by HB were enrolled. We used the DHPLC technique followed by direct sequencing of suspected segments to detect FIX gene mutations. In all, 11 FIX gene mutations (8 point mutations, 2 small deletions/insertions, and 1 large deletion), including two novel mutations (exon6 c.687–695, del 9 mer and c.460–461, ins T) were found. According to the HB pedigrees, 25% and 75% of our patients were defined as familial and sporadic HB cases, respectively. We show that DHPLC is a highly sensitive and cost-effective method for FIX gene analysis and can be used as a convenient system for disease prevention.
Abstract Objective We describe a prenatal molecular diagnosis of hypochondroplasia (HCH) in a pregnancy not at risk of HCH and review the literature on prenatal diagnosis of HCH. Case report A ...28-year-old primigravid woman was referred for genetic counseling at 30 weeks of gestation because of short-limbed dwarfism in the fetus. The woman had a body height of 152 cm. Her husband had a body height of 180 cm. Level II ultrasound showed a normal amount of amniotic fluid and a singleton fetus with fetal biometry equivalent to 30 weeks except for short limbs. Fetal biometry measurements were as follows: biparietal diameter = 7.38 cm (30 weeks); head circumference = 28.14 cm (30 weeks); abdominal circumference (AC) = 24.64 cm (30 weeks); femur length (FL) = 3.97 cm (<5th centile); FL/AC ratio = 0.161 (normal > 0.18); humerus = 3.64 cm (<5th centile); radius = 3.49 cm (30 weeks); ulna = 3.76 cm (<5th centile); tibia = 3.67 cm (<5th centile); and fibula = 3.72 cm (<5th centile). The digits and craniofacial appearance were normal. A tentative diagnosis of achondroplasia (ACH) was made. DNA testing for the FGFR3 gene and whole-genome array comparative genomic hybridization (aCGH) analysis were performed using cord blood DNA obtained by cordocentesis. FGFR3 mutation analysis revealed a de novo heterozygous c.833A > G, TAC > TGC transversion in exon 7 leading to a p.Tyr278Cys (Y278C) mutation in the FGFR3 protein. aCGH analysis revealed no genomic imbalance in cord blood. After delivery, the fetus had short limbs, a narrow thorax, brachydactyly, and relative macrocephaly. Cytogenetic analysis of cultured placental cells revealed a karyotype of 46,XX. Conclusion Prenatal diagnosis of abnormal ultrasound findings suspicious of ACH should include a differential diagnosis of HCH by molecular analysis of FGFR3.
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