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Tsang-Ming Ko

Publications and source records attributed to Tsang-Ming Ko.

9 recordsLinked to original sources
PubMed2006

A novel heterozygous missense mutation 377T > C (V126A) of TGIF gene in a family segregated with holoprosencephaly and moyamoya disease.

OBJECTIVES: To identify whether any mutations of candidate genes including SHH, ZIC2, SIX3, and TGIF exist in a Taiwanese family segregated with holoprosencephaly (HPE) and moyamoya disease. METHODS: Genotypes of the candidate genes SHH, ZIC2, SIX3, and TGIF were determined in the family members who were available for analysis by sequencing. In addition, genomic regions of another 50 unrelated Taiwanese (100 chromosomes) were studied to verify whether the nucleotide changes we found were mutations or polymorphisms. RESULTS: A novel missense mutation 377T > C and two polymorphisms (420A > G and 487C > T) in the TGIF gene were identified. No mutations in SHH, ZIC2 and SIX3 were found. The mother of the three HPE fetuses was found to be afflicted with moyamoya disease. A brief review of the mutations as well as polymorphisms reported in the TGIF gene up to 2005 is given. CONCLUSION: Molecular diagnosis can help genetic counseling in HPE, which is a heterogeneous disorder with its phenotypic and genotypic spectrum highly widened and variable. The possible association between TGIF mutation and moyamoya disease noted in our study also appeared to be novel.

Adult↗
PubMed2006

Prenatal diagnosis and genetic analysis of a fetus with 47,XX,+21/46,XX mosaicism and XX/XY chimerism.

Prenatal diagnosis of simultaneous occurrence of chimerism and autosomal mosaicism is extremely rare. We report the prenatal diagnosis and genetic analysis of a fetus in a twin pregnancy with mosaic 47,XX,+21/46,XX with chimeric XX/XY. A 36-year-old, para 1, woman was referred for genetic counseling at 20 weeks' gestation because of abnormal karyotype (47,XX,+21/46,XX) in one fetus in a twin pregnancy. Cordocentesis revealed 47,XX,+21[3]/46,XX[35]/46,XY[7] in this fetus. Postnatal cytogenetic analysis of cord blood confirmed three cell lines in this twin (A) and 46,XY in the co-twin (B). Postmortem pathologic findings of both fetuses were normal. Fluorescence in situ hybridization identified three cell lines in the cord blood of twin A. Molecular genetic analysis using polymorphic DNA markers revealed parental origin of fetal tissue, and confirmed the chimeric status. Molecular genetic analysis with polymorphic DNA markers help to differentiate chimerism from mosaicism and define the origin of cell lines, which may have importance in genetic counseling.

Adult↗
PubMed2005

Prenatal diagnosis and molecular cytogenetic analysis of partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter) in a fetus associated with cystic hygroma and ambiguous genitalia.

OBJECTIVES: To present the prenatal diagnosis and molecular cytogenetic analysis of a fetus with nuchal cystic hygroma and ambiguous genitalia. CASE AND METHODS: Amniocentesis was performed at 16 weeks' gestation because of the abnormal fetal sonographic finding of a large septated nuchal cystic hygroma. Genetic amniocentesis revealed a terminal deletion in the long arm of chromosome 10. The paternal karyotype was subsequently found to be 46,XY,t(10;18)(q25.3;q23). The maternal karyotype was normal. The pregnancy was terminated. A hydropic fetus was delivered with a septated nuchal cystic hygroma and ambiguous genitalia. Fluorescence in situ hybridization (FISH), microarray-based comparative genomic hybridization (CGH), and polymorphic DNA markers were used to investigate the involved chromosomal segments. RESULTS: FISH study showed absence of the 10q telomeric probe and presence of the 18q telomeric probe in the derivative chromosome 10. Microarray-based CGH analysis showed loss of distal 10q and gain of distal 18q. Polymorphic DNA marker analysis determined the breakpoints. The fetal karyotype was 46,XY,der(10)t(10;18)(q25.3;q23)pat. The chromosome aberration resulted in partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter). CONCLUSIONS: The present case provides evidence that partial monosomy 10q (10q25.3-->qter) with partial trisomy 18q (18q23-->qter) can be a genetic cause of fetal cystic hygroma and ambiguous genitalia. Cytogenetic analysis for prenatally detected structural abnormalities may detect unexpected inherited chromosome aberrations.

Adult↗
PubMed2004

Prenatal diagnosis of mos46,X,del(Y)(q11.2)/45,X by cytogenetic and molecular studies with multiplex STR analysis.

OBJECTIVES: To present the prenatal diagnosis of a fetus of mos46,X,del(Y)(q11.2)/45,X by cytogenetic and molecular analysis. CASE AND METHODS: A 35-year-old pregnant woman came to our hospital for amniocentesis, and fetal chromosomal aberrations with mos46,X, + mar/45,X were found. Fluorescence in situ hybridization revealed the existence of a Y centromere on the marker chromosome. Analysis with six pairs of short tandem repeat markers showed that the genomic DNA extracted from the uncultured amniotic fluid cells contained a deletion of Yq11.1-Yq11.2. Spermatogenesis loci of the Y chromosome were studied using four sets of multiplex PCR. The proximal two markers DYS271 and KALY were present and the other 16 distal markers were deleted. No deletion was noted in the Y chromosome of the father. RESULTS: Cytogenetic and molecular analyses revealed deletions of AZFb, d, and c regions on Yq11.2-Yqter in the fetal Y chromosome. Postmortem examination of the fetus showed a grossly normal male fetus with normal external genitalia and testes. CONCLUSION: The present report demonstrates that molecular analysis using polymorphic microsatellite markers and multiplex PCR is a useful complement to cytogenetic methods for the identification and the characterization of Y-chromosomal deletions.

Adult↗
PubMed2004

Evaluation of second trimester maternal serum screening for Down's Syndrome using the Spiegelhalter-Knill-Jones (S-KJ) approach.

AIMS: Risk estimation for Down's syndrome in antenatal serum screening with maternal age and multiple serum biomarkers is usually complicated and computationally intensive. We have developed a simple scoring system using the Spiegelhalter-Knill-Jones approach, which was based on Bayesian theorem and the logistic regression model. METHODS: A prospective data set with 3842 singleton pregnancies including 6 affected pregnancies served as "trained data". Maternal age, maternal serum alpha-fetoprotein and human chorionic gonadotrophin levels of each pregnant woman were adopted as the predictors to establish the scoring model using the S-KJ approach. Model validation was undertaken using a receiver operating characteristics (ROC) curve with another 3050 singleton pregnancies including 4 affected pregnancies ("validated data"). RESULTS: For the trained data the sensitivity and specificity of the scoring system at cut-off value of 1:250 was 66.7% and 92.6%, respectively. For the validated data the sensitivity and specificity at the same cut-off point was 75% and 92.2%, respectively. The area under the ROC curve of the trained and validated data was 76.96% (95% CI: 51.80-100%), and 94.07% (95% CI: 84.47-100%), respectively. CONCLUSIONS: The S-KJ scoring system has been demonstrated to be a simple, and efficient method for the risk estimation of Down's syndrome. This system can be applied to other antenatal serum screening systems.

Adult↗
PubMed2004

Fetal gender determination using real-time quantitative polymerase chain reaction analysis of maternal plasma.

BACKGROUND AND PURPOSE: Cell-free fetal DNA in maternal blood is a promising non-invasive alternative for prenatal diagnosis. The goal of this study was to determine fetal sex with maternal plasma in pregnant women without previous male offspring. METHODS: Blood samples (3 mL) were collected at 6 to 16 weeks' gestation from 56 healthy pregnant women without previous male offspring. There were 23 pregnancies with male fetuses and 33 pregnancies with female fetuses. DNA was extracted from plasma and qualitative analysis of the sex-determining region Y (SRY) gene sequence on the Y chromosome (SRY-3317T) with dual-labeled fluorescent TaqMan probe using real-time quantitative polymerase chain reaction (PCR) was performed. RESULTS: In the 56 successfully assayed samples, SRY-positive signals were detected in 20 samples of the 23 pregnancies with male fetuses. None of the 33 successfully assayed samples from women bearing female fetuses yielded a positive signal. CONCLUSIONS: Because of its high correct prediction rate, fetal gender determination with maternal plasma using real-time quantitative PCR can be used as a pre-test to avoid unnecessary chorionic villus sampling for pregnancies at risk of fetal sex-associated disorders.

Adult↗
PubMedDate not supplied

Mutation spectrum of the connexin 26 (GJB2) gene in Taiwanese patients with prelingual deafness.

PURPOSE: To determine the mutation spectrum of the connexin 26 gene among 324 Taiwanese patients with prelingual deafness and the carrier rate of gene mutation in another 432 unrelated control subjects. METHODS: The coding region of the connexin 26 gene was sequenced in both directions to detect mutation in all 756 samples. RESULTS: Among the 756 samples tested, 21 connexin 26 variants were detected, including 7 novel ones. The 235delC mutation was the most common, accounting for 57.6% of the mutant alleles. Among patients, 48 (14.8%) had connexin 26 gene mutations. In the control group, the carrier rate of connexin 26 mutation was estimated at 2.8%. CONCLUSION: The mutation spectrum of the connexin 26 gene is wide, with more than half of the patients having only one mutation detected. Thus, further efforts are needed to look for possible existence of a second mutant allele.

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