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Objective:To analyze fetal sex chromosome abnormalities in prenatal diagnosis based on amniotic fluid cell culture.Methods:Clinical data of 12 164 pregnant women who underwent amniocentesis in Maternal and Child Health Hospital of Hunan Province from January 2017 to December 2020 were retrospectively analyzed. For those diagnosed with fetal sex chromosome abnormalities, the results of karyotyping and chromosome microarray analysis (CMA) were analyzed and described.Results:(1) Among the 12 164 cases, fetal sex chromosome abnormalities were detected in 387 cases (3.2%), including 351 cases with abnormal sex chromosome karyotype and 36 with sex chromosome microdeletion/microduplication. (2) High-risk patients indicated by non-invasive prenatal test (NIPT) had the highest proportion of sex chromosomes abnormalities (74.2%, 287/387), followed by those with other ultrasound abnormalities (8.5%, 33/387), high risk of Down syndrome screening (7.0%, 27/387), advanced maternal age (4.7%, 18/387), history of adverse pregnant or delivery (3.3%, 13/387), and nuchal translucency thickening or cervical lymphatic hygroma (2.3%, 9/387). (3) Detected chromosome karyotype abnormalities included numerical abnormalities [73.2%(257/351)], mosaicism [18.8(66/351)], and structural abnormalities [8.0%(28/351)], among which, 47,XXY [46.7%(120/257)], 45,X/46,XX[48.5%(32/66)], and X chromosome deletion [39.3%(11/28)] were the most common, respectively. Among 36 sex chromosome microdeletions/microduplications cases, 15(41.7%) were with pathogenic copy number variation (CNV), including 14 cases of X chromosome microdeletion/microduplication; 7(19.4%) with benign CNV, and 14(38.9%) with CNV of unknown clinical significance. The fragment size [ M (min-max)] of the 15 pathogenic CNV was 1.68 Mb(0.37-9.20 Mb). Of the nine cases with microdeletions, seven were found with deletion in the Xp22.31 region. Conclusions:Numerical abnormalities are the most common fetal sex chromosome abnormalities detected from amniotic fluid samples. Others included mosaicism and chromosome structure abnormalities.
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Objective:To investigate the power and prenatal diagnosis strategies of cell-free fetal DNA (cffDNA) testing for chromosomal aneuploidy screening apart from trisomy-13/18/21.Methods:This study collected the clinical data of three cases at high risk of trisomy-16 indicated by cffDNA testing in Hunan Provincial Maternal and Child Health Care Hospital from March 2019 to March 2020. Results of the conventional G-banding karyotype analysis of amniotic fluid, single nucleotide polymorphism array (SNP-array) and low-coverage massively parallel copy number variation sequencing (CNV-seq) of placenta/fetal skin samples were analyzed.Results:(1) cffDNA testing results suggested that case 1-3 were at high risk of trisomy-16 and the Z values of chromosome 16 were 20.57, 24.88 and 17.87, respectively. (2) Karyotype analysis of amniotic fluid samples did not identify any abnormalities in Case 1 and 2, while SNP-array revealed a 19.2 Mb and 23.0 Mb heterozygous deletion at 16p13.3p12.3 and 16q22.1q24.3 in Case 1, and a 16.0 Mb loss of heterozygosity at 16q22.3q24.3 in Case 2. Case 3 had a mosaicism karyotype of 47,XY,+16[3]/46,XY[97] and SNP-array analysis showed no heterozygous deletion greater than 5 Mb or copy number variation. (3) Ultrasonography indicated fetal growth restriction in Case 1 and 2 and fetal death in Case 3. All three pregnancies were terminated. CNV-seq analysis of placental tissue in the center of both fetal and maternal side revealed mosaic trisomy 16, with the copy numbers of chromosome 16 of 2.56/2.70, 2.73/2.82, 2.80/2.81, respectively. However, no copy number variation was detected in Case 1 or 2 by CNV-seq analysis of fetal skin tissues. Conclusions:cffDNA testing has a certain power in detecting trisomy-16 apart from trisomy-13/18/21. For high-risk cases of trisomy-16 indicated by cffDNA testing, SNP-array analysis combined with karyotype analysis is suggested to rule out low-level mosaicism and loss of heterozygosity.
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Objective:To analyze the prenatal ultrasound manifestation of trisomy 21 syndrome and investigate the clinical significance of prenatal ultrasound in screening 21-trisomy syndrome.Methods:A retrospective analysis of prenatal ultrasound results of 200 fetuses diagnosed with 21-trisomy syndrome by karyotype from May 2017 to August 2018 in Hunan Provincial Maternal and Child Health Care Hospital. Ultrasound abnormalities were divided into isolated soft markers, simple structural abnormalities, complex ultrasound markers. The relationship between these markers and trisomy 21 was analysed.Results:200 fetuses with trisomy 21 syndrome diagnosed by karyotype, in which 39 cases (19.5%, 39/200) abnormalities were detected by ultrasound, including soft indexes and structural abnormalities/other abnormalities. The rates of isolated soft indexes, simple structural abnormalities/ other abnormalities and complex ultrasound markers were 15.5%(31/200), 2.0%(4/200), 2.0%(4/200), respectively. The most common of soft markers in the first trimester was thickened nuchal translucency (4/18), thickened nuchal fold (13.19%, 24/182) in the second trimester, followed by nasal bone dysplasia, tricuspid regurgitation and polyhydramnios (1.65%, 3/182). The most common structural malformations in the second trimester was cardiovascular malformation (3.30%, 6/182).Conclusions:Prenatal ultrasound has a role to play in the screening of 21-trisomy syndrome, but exerts certain limitations. It is necessary to strengthen the understanding of the ultrasonographic features of trisomy 21 and improve the detection rate of abnormal indicators. Meanwhile, it should be combined with serological screening, non-invasive prenatal testing technology to increase the detection rate of trisomy 21.
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A patient with global developmental delay and facial abnormality treated in Hunan Maternal and Child Health Care Hospital in September 2018 was diagnosed as a typical Say-Barber-Biesecker/Young-Simpson syndrome (SBBYSS)accompanied with comprehensive clinical manifestations and genetic testing was carried out.The patient carries a heterozygous synonymous mutation of KAT6B gene (NM_012330.3)c.3147G>A (p.P1049P), thus leading to the formation of a new cleavage site (receptor) and forming a new truncated protein.In Chinese, this is the second typical SBBYSS that has been identified and the first prenatal genetic diagnosis has been performed.This study has broadened the mutation spectrum of SBBYSS caused by the mutation of KAT6B gene in Chinese population.
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OBJECTIVE@#To explore the genetic basis for a patient with premature ovarian insufficiency.@*METHODS@#Chromosomal G-banding and C-banding, single nucleotide polymorphism array (SNP-array), fluorescence in situ hybridization (FISH) and Y chromosome microdeletion assay were used for the analysis.@*RESULTS@#With the combined techniques, the patient was found to carry a Xq;Yq translocation, with a karyotype of 46,X,der(X)t(X;Y)(q25;q12).ish der(X)(Tel XYp+,Tel XYq+,Yq12+).@*CONCLUSION@#Unbalanced Xq;Yq translocation probably underlay the premature ovarian insufficiency in this patient.
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OBJECTIVE@#To carry out prenatal diagnosis for a fetus with high risk predicted by non-invasive prenatal testing (NIPT).@*METHODS@#Next-generation sequencing (NGS) was used to analyze free fetal DNA (ffDNA) in the maternal plasma. Chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) were used to ascertain copy number variation in the fetus and its parents.@*RESULTS@#SNP-array analysis and chromosomal karyotyping revealed that the fetus had a 15.018 Mb duplication at 4q34.1q35.2 and a 7.678 Mb duplication at 21q11.2q21.1, which were derived from a t(4;21)(q34.1;q21.1) translocation carried by its mother.@*CONCLUSION@#NIPT is capable of detecting submicroscopic chromosomal abnormalities of the fetus. Combined use of genetic techniques, in particular SNP-array, is crucial for the diagnosis of partial trisomy 21q in this case.
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OBJECTIVE@#To explore the genetic etiology of a pedigree with mental retardation and hypotonia by using chromosome microarray analysis (CMA), low coverage massive parallel copy number variation sequencing (CNV-seq) and quantitative PCR (qPCR).@*METHODS@#Genomic DNA was extracted from peripheral blood samples from two male patients and healthy members from the pedigree. CNV-seq was carried out for one patient. Suspected CNV was verified by qPCR. CNV-seq or single nucleotide polymorphism array (SNP array) were carried out for another patient and his family members.@*RESULTS@#Both patients showed severe hypotonia and global development delay, in particular language delay. CNV-seq and SNP array indicated that both patients had carried a Xq28 duplication, with spanned 0.26 Mb and 0.42 Mb, respectively. Both duplications encompassed the MECP2 gene. CNV-seq analysis of their family members confirmed that the mother and one sister had carried similar duplications, while an elder brother was normal.@*CONCLUSION@#CNV-seq and CMA are rapid and effective tools for the diagnosis of MECP2 duplication syndrome in children with mental retardation, hypotonia and recurrent infections.
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Objective@#To investigate the genetic etiology of neurodevelopmental disorders (NDD), and to provide a theoretical basis for its genetic counseling, family risk evaluation and prenatal diagnosis.@*Methods@#Karyotype analysis and chromosome microarray analysis (CMA) were conducted of the data from 420 children diagnosed accor-ding to NDD diagnostic criteria at Maternal and Child Health Hospital of Hunan Province from January 2016 to December 2018.@*Results@#Among the 420 cases, 14 cases (3.33%, 14/420 cases) with global developmental disabilities/intellectual disabilities (GDD/ID) had chromosomal abnormalities.The location of chromosome breakpoints and the range of deleted or duplicated fragments in 13 cases were further determined by using CMA.In this study, pathogenic copy number variations (CNVs) were detected in 61 children (14.52%, 61/420 cases), which included 31 cases (50.82%, 31/61 cases) of known syndromes, including Angelman/Prader-Will syndrome (8 cases), Williams syndrome (3 cases), Phelan-McDermid syndrome (3 cases) and other 13 syndromes, and 30 cases with clinically significant pathogenic CNVs.Additionally, by the combination of CMA and fluorescence in situ hybridization (FISH), a family were diagnosed with mental retardation caused by 10q26 and 12p13 occult rearrangement.@*Conclusions@#Chromosomal abnormalities and genomic microdeletion/duplication are the primary genetic causes for children with NDD.Combination of karyotype analysis, CMA and FISH can provide definite etiological diagnosis for these children, which has important clinical signi-ficance for the treatment of children and guidance of their parents′ reproduction.
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Objective@#To investigate the prevalence, mutation characteristics and clinical outcomes of inherited metabolic diseases(IMD) by using tandem mass spectrometry screening.@*Methods@#In Hunan province, 565 182 newborns who underwent tandem mass spectrometry (MS/MS) screening for IMDs were studied, including fatty acid oxidation disorders (FAODs), amino acid disorders (AAs), and organic acidemias (OAs) between March 2013 and September 2017.For the patients with positive results, a recall screening test was performed, and the results were further confirmed by specific biochemical and genetic analysis.For all the patients with IMD, guideline-directed medical treatment was administrated, and the follow-up outcomes was evaluated.@*Results@#A total of 107 newborns were diagnosed with IMDs, with an overall prevalence of 1∶5 282, including 65 newborns with FAODs (1∶ 8 695), 29 newborns with AAs (1∶19 489), and 13 newborns with OAs (1∶43 476). The primary carnitine deficiency(PCD)(44 cases), hyperphenylalaninemia (HPA)(17 cases), short-chain acyl-CoA dehydrogenase deficiency(SCADD)(12 cases), citrine deficiency(NICCD)(6 cases) were the 4 most common IMDs in Hunan province.The hotspot mutations in SLC22A5 gene of PCD were c. 51C>G(25.3%), c.1400C>G(23.0%), and c. 760C>T(13.8%); in PAH gene of HPA were c. 728G>A (22.2%) and c. 721C>T(14.8%); in ACADS gene of SCADD was c. 1031A>G(38.9%); and in SLC25A13 gene of NICCD was c. 851_854delGTAT (50.0%), respectively.The remaining IMDs were rare, and the hotspot mutations were unclear right now.During a mean follow-up of (26.1±5.6) months, 7 patients died, 4 patients suffered an intelligent disability, whereas the remaining 96 subjects had normal physical and intelligent development.@*Conclusions@#The overall prevalence of IMDs is not fairly low in Hunan province.Newborn screening and early appropriate management can significantly improve the outcomes of these patients.
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Objective@#To carry out genetic testing for a boy presenting with mental retardation and hypoplasia.@*Methods@#Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism based array (SNP-array) were used to analyze the boy and his parents.@*Results@#SNP-array has detected a 25.7 Mb microduplication at 2q33.3q36.3 in the boy. Chromosomal karyotyping and FISH analysis indicated that his mother had a karyotype of 46, XX, ish ins(11; 2)(p15; q33q36), and that the boy has carried an abnormal chromosome 11 derived from the maternal translocation. The karyotype of the boy was ascertained as 46, XY, ish der(11)ins(11; 2)(p15; q33q36)mat.@*Conclusion@#SNP-array combined with G-banding and FISH can delineate the cryptic translocation and is valuable for the assessment of recurrence risk for subsequent pregnancies.
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OBJECTIVE@#To carry out genetic testing for a boy presenting with mental retardation and hypoplasia.@*METHODS@#Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism based array (SNP-array) were used to analyze the boy and his parents.@*RESULTS@#SNP-array has detected a 25.7 Mb microduplication at 2q33.3q36.3 in the boy. Chromosomal karyotyping and FISH analysis indicated that his mother had a karyotype of 46,XX,ish ins(11;2) (p15;q33q36), and that the boy has carried an abnormal chromosome 11 derived from the maternal translocation. The karyotype of the boy was ascertained as 46,XY,ish der(11)ins(11;2) (p15;q33q36)mat.@*CONCLUSION@#SNP-array combined with G-banding and FISH can delineate the cryptic translocation and is valuable for the assessment of recurrence risk for subsequent pregnancies.
Subject(s)
Child , Female , Humans , Male , Pregnancy , Chromosome Banding , Chromosome Duplication , Genetic Testing , Hypospadias , Genetics , In Situ Hybridization, Fluorescence , Intellectual Disability , Genetics , Karyotyping , Polymorphism, Single Nucleotide , Translocation, GeneticABSTRACT
OBJECTIVE@#To explore the prenatal screening and diagnosis for a pair of monochorionic-diamniotic (MCDA) twins discordant for 45,X/46,XX mosaicism.@*METHODS@#Amniotic fluid samples were taken from both twins for whom non-invasive prenatal testing has signaled a high risk for sex chromosomal abnormality. Uncultured amniotic fluid was analyzed by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array). Conventional G-banded karyotyping analysis was performed on the cultured amniotic fluid.@*RESULTS@#Metaphase chromosome analysis showed that one of the twins had a mos 45,X[11]/46,XX[26] karyotype, while the other had a normal karyotype. FISH and SNP-array applied on uncultured amniotic fluid revealed about 30% mosaicism in one of the twins. The twins were confirmed to be monozygotic by SNP-array analysis.@*CONCLUSION@#To avoid confusion arising from discordant karyotypes in MCDA twins with abnormal non-invasive prenatal testing (NIPT) results, dual amniocentesis should be carried out to obtain amniotic fluid samples for chromosomal as well as molecular analysis. To determine the ratio of 45,X and 46,XX cells in Turner syndrome can provide valuable information for prenatal genetic counseling.
Subject(s)
Female , Humans , Pregnancy , Amniocentesis , Chromosomes, Human, X , In Situ Hybridization, Fluorescence , Karyotyping , Mosaicism , Prenatal DiagnosisABSTRACT
OBJECTIVE@#To explore the genetic basis of a child featuring intellectual disability, developmental delay and epilepsy.@*METHODS@#Cytogenetic and molecular analysis including chromosomal karyotyping analysis, single nucleotide polymorphism array (SNP array) and qPCR were performed.@*RESULTS@#The karyotype of the child was determined as 46, XX; SNP array: arr [19]21q22.12q22.13(36 860 195-38 801 482)×1 dn. A heterozygous 1.9 Mb microdeletion was detected at 21q22.12q22.13. qPCR has confirmed deletion of exon 1 of the DYRK1A gene, which has occurred de novo.@*CONCLUSION@#A 21q22 deletion was diagnosed with multiple genetic methods. Genotype-phenotype correlation suggested DYRK1A to be a candidate for intellectual disability.
Subject(s)
Child , Humans , Developmental Disabilities , Genetics , Epilepsy , Genetics , Genetic Association Studies , Intellectual Disability , Genetics , Karyotyping , Protein Serine-Threonine Kinases , Genetics , Protein-Tyrosine Kinases , Genetics , Sequence DeletionABSTRACT
Objective To investigate the prevalence,mutation characteristics and clinical outcomes of inherited metabolic diseases(IMD) by using tandem mass spectrometry screening.Methods In Hunan province,565 182 newborns who underwent tandem mass spectrometry (MS/MS) screening for IMDs were studied,including fatty acid oxidation disorders (FAODs),amino acid disorders (AAs),and organic acidemias (OAs) between March 2013 and September 2017.For the patients with positive results,a recall screening test was performed,and the results were further confirmed by specific biochemical and genetic analysis.For all the patients with IMD,guideline-directed medical treatment was administrated,and the follow-up outcomes was evaluated.Results A total of 107 newborns were diagnosed with IMDs,with an overall prevalence of 1 ∶ 5 282,including 65 newborns with FAODs (1 ∶ 8 695),29 newborns with AAs (1 ∶ 19 489),and 13 newborns with OAs (1 ∶ 43 476).The primary carnitine deficiency(PCD) (44 cases),hyperphenylalaninemia (HPA) (17 cases),short-chain acyl-CoA dehydrogenase deficiency (SCADD) (12 cases),citrine deficiency(NICCD)(6 cases) were the 4 most common IMDs in Hunan province.The hotspot mutations in SLC22A5 gene of PCD were c.51C ＞ G(25.3％),c.1400C ＞ G(23.0％),and c.760C ＞ T(13.8％);in PAH gene of HPA were c.728G ＞ A (22.2％) and c.721C ＞ T(14.8％);in ACADS gene of SCADD was c.1031A ＞ G(38.9％);and in SLC25A13 gene of NICCD was c.851_854delGTAT (50.0％),respectively.The remaining IMDs were rare,and the hotspot mutations were unclear right now.During a mean follow-up of (26.1 ± 5.6) months,7 patients died,4 patients suffered an intelligent disability,whereas the remaining 96 subjects had normal physical and intelligent devdopment.Conclusions The overall prevalence of IMDs is not fairly low in Hunan province.Newborn screening and early appropriate management can significantly improve the outcomes of these patients.
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<p><b>OBJECTIVE</b>To assess the value of genetic testing for Fragile X syndrome (FXS).</p><p><b>METHODS</b>A domestically made diagnostic kit based Tri-primer-PCR method was used to detect mutations of the FMR1 gene among 6 pedigrees with unexplained intellectual disability. The results were verified by methylation PCR and Southern blotting.</p><p><b>RESULTS</b>Pedigrees 1 and 6 were positive for the screening. In pedigree 1, a full-mutation allele with methylation was identified in the proband and his mother, which was passed on to the fetus. In pedigree 6, the proband was mosaic for a full-mutation allele and a pre-mutation allele. His sister was asymptomatic with a full-mutation. His mother carried pre-mutation allele, while his father and sister's baby were normal. The number of CGG repeats of the pedigrees 2 to 5 were in the normal range.</p><p><b>CONCLUSION</b>Genetic testing can provide an effective way to prevent FXS caused by FMR1 mutations and enable prenatal diagnosis for families with a high risk for the disease.</p>
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<p><b>OBJECTIVE</b>To investigate the phenotype-genotype association of isodicentromere Y chromosome by analysis of two female patients carrying the chromosome with sexual development disorders.</p><p><b>METHODS</b>The karyotypes of the two patients were determined by application of conventional G banding of peripheral blood samples and fluorescence in situ hybridization (FISH). PCR was applied to detect the presence of SRY gene.</p><p><b>RESULTS</b>Conventional karyotype analysis showed case 1 to be a mosaic: mos.45,X[38]/46,X,+mar[151]/47,XY,+mar[5]/47,X,+mar × 2[2]/46,XY[4], FISH showed that 12 different cell lines were presented in the karyotype of case 1 and partial cell lines with SRY gene, the marker is an isodicentromere Y chromosome [idic(Y)(p)]. No mutation was found in the SRY gene. The karyotype of case 2 was mos.45,X[25]/46,X,+mar[35]. FISH showed the marker to be an idic(Y)(p) without the SRY gene.</p><p><b>CONCLUSION</b>The karyotype of patients carrying idic(Y)(p) seems unstable, and female patients have the characteristics of short stature and secondary sexual hypoplasia. Karyotype analysis combined with FISH analysis can accurately determine the breakpoint of idic(Y) and identify the types of complex mosaic, which may facilitate genetic counseling and prognosis.</p>
Subject(s)
Adolescent , Child , Female , Humans , Chromosomes, Human, Y , Disorders of Sex Development , Genetics , Karyotype , Sex Chromosome Aberrations , Sex-Determining Region Y Protein , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies.</p><p><b>METHODS</b>Plasma from 4004 women with singleton pregnancy at a gestational age between 12-35(+5) weeks was collected prior to amniocentesis between April 19th 2011 and December 31st 2013. The samples were divided into three groups: (1) High risk for Down syndrome by biochemical screening; (2) Advanced maternal age; (3) Abnormalities by ultrasound or other methods. Plasma DNA extracted from above samples was sequenced at low coverage. Positive results were verified against the karyotypes of the fetuses. For those with negative results, the fetuses were followed up by telephone call for at least six months after birth.</p><p><b>RESULTS</b>Among 4003 samples subjected to non-invasive prenatal diagnosis, 66 (1.65%) had a positive result. In group 1, 22 cases of trisomy 21 (T21), 3 cases of trisomy 18 (T18), 1 case of 13 trisomy (T13), 8 cases of 45,X and 2 cases of other chromosomal abnormality were detected. In group 2, 13 cases of T21, 2 cases of T18, 1 case of T13, 5 cases of 45,X, 2 cases of 47,XXN and 1 case of other chromosomal abnormality were detected. In group 3, 1 case of T21, 1 case of T18, 1 case of T13, and 3 cases of 47,XXN were detected. For 55 samples underwent prenatal diagnosis, 30 cases of T21 and 4 cases of T18 were discovered, which was consistent with the results of non-invasive prenatal diagnosis. For the 13 cases indicated as 45,X, 3 were verified by karyotype analysis, 2 were verified as mosaicism (45,X/46,XN), 8 were 46,XN (false positives). For the 5 cases indicated as 47,XXN, 2 were verified by karyotype analysis, the other 3 were 46,XN (false positives). Karyotypes of 3 cases suspected for other chromosomal abnormalities were all verified as 46,XN (false positive). Until May 1st 2014, telephone follow-up for those with negative screening results only identified a boy with facial abnormalities and developmental delay, which was similar to his older sister, combined karyotyping and fluorescence in situ hybridization analysis has verified the karyotype of the boy as 46,XY,rec(14)dup(14q)inv(14)(p12q14)pat.</p><p><b>CONCLUSION</b>Our results indicated that sequencing of plasma free DNA can rapidly detect fetal chromosomal aneuploidies. The method is non-invasive, and the results are highly consistent with karyotype analysis in terms of accuracy and specificity. Non-invasive testing can be used as an effective adjunct to conventional prenatal diagnostic methods, which can greatly reduce unnecessary invasive prenatal diagnosis. However, the sensitivity and accuracy for aneuploidy detection other than chromosome 13/18/21 still need to be improved.</p>
Subject(s)
Adult , Female , Humans , Infant , Male , Pregnancy , Aneuploidy , Asian People , Genetics , China , Chromosomes, Human, Pair 18 , Genetics , Chromosomes, Human, Pair 21 , Genetics , Chromosomes, Human, Pair 8 , Genetics , Down Syndrome , Diagnosis , Embryology , Genetics , Fetal Diseases , Diagnosis , Genetics , High-Throughput Nucleotide Sequencing , Methods , Pedigree , Prenatal Diagnosis , MethodsABSTRACT
<p><b>OBJECTIVE</b>To perform genotyping analysis and subsequent prenatal genetic diagnosis for two families affected with oculocutaneous albinism (OCA).</p><p><b>METHODS</b>Direct sequencing of TYR and P genes was performed in two albino probands. Family members were screened for corresponding mutant alleles. Prenatal genetic diagnoses were performed at early pregnancy by chorionic villus sampling (CVS) at mid-pregnancy through amniocentesis.</p><p><b>RESULTS</b>No mutations were detected in the TYR gene in either probands, whereas 4 heterozygous mutations of the P gene were found, namely c.406C>T, c.535A>G, c.808-2A>G and c.2180T>C, among which c.535A>G and c.808-2A>G were novel. In the first round prenatal genetic testing, both fetuses were found to have the same genotypes as the probands. Both families had decided to terminate the pregnancy after genetic counseling. In the second round testing, neither of the fetuses was found to be affected by genotyping. The pregnancies continued and two healthy fetuses were born.</p><p><b>CONCLUSION</b>OCA can be classified by genotyping, with which reliable prenatal diagnosis and feasible genetic counseling may be provided.</p>
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Pregnancy , Young Adult , Albinism, Oculocutaneous , Diagnosis , Embryology , Genetics , Asian People , Genetics , Base Sequence , Fetal Diseases , Diagnosis , Genetics , Genotype , Membrane Transport Proteins , Genetics , Molecular Sequence Data , Monophenol Monooxygenase , Genetics , Pedigree , Point Mutation , Prenatal DiagnosisABSTRACT
Objective To study the relation between the HPV6/18 virus infection and the development of pathological changes of cervix. Methods The number of HPV16/18 DNA copies and the expression rate of HPV16/18 E7 mRNA in the pathological cervix were examined by the quantitative fluorescent PCR combined with pathological diagnosis and immunohistochemistry staining. Results The HPV16 infection rates in chronic cervicitis group were much lower (7.4%) than that in the cervical intraepithelial neoplasia (CIN) groups and the cervical cancer group (69.6% and 72.7%), respectively. Statistical analysis showed that the difference of HPV16 DNA copies was not significant between the chronic cervicitis group and CIN groups. In contrast to the above mentioned result, the number of HPV DNA copies between the CIN groups and the cervical cancer group was significantly different. The HPV16 E7 gene expression rates in CIN Ⅰ, Ⅱ, Ⅲ and cervical cancer groups were 0,37.5%,42.9%,63.6%, respectively. Conclusion Ins more common than that with HPV18. The number of HPV16 DNA copies in cervical cancer tissues is markedly higher than that in CIN Ⅱ, Ⅲ groups. The HPV16 E7 mRNA expression is significantly increased in the cervical cancer, and it is more closely correlated to this pathological changes. The quantitative fluorescent PCR can be used to reflect the activity of HPV, and it is a useful method for the screening examination of HPV and for the early diagnosis and treatment of cervical caner.