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1.
Article in Chinese | WPRIM | ID: wpr-885862

ABSTRACT

Objective:To observe and analyze the pathogenic gene types and clinical phenotypes of Leber congenital amaurosis (LCA).Methods:A retrospective clinical study. Six patients with LCA confirmed by genetic testing and 18 family members were included in the study. The patients came from six unrelated families. The family was investigated with a specific hereditary eye disease enrichment panel which contained 463 known pathogenic genes and based on targeted exome capture technology first to indentify the potential pathogenic genes and mutations. Then the TULP1 , RPGRIP1 , GUCY2D pathogenic mutations were conformed by Sanger sequencing. The pathogenicity of the gene variation was searched through relevant databases and PubMed literature, and its function was explained by protein prediction software. Results:Of the 6 patients, 3 were males and 3 were females; the age was from 3 to 33 years. Nystagmus, finger pressing eyes, photophobia, and night blindness were seen in 5 cases; electroretinogram showed 3 cases of extinction or near extinction; and 4 cases of retinopathy. The results showed patients with compound heterozygous mutation of c.1318C> T and c.1142T> G, homozygous mutation ofc.1318C> T and compound heterozygous mutation of c.1153G> A and c.1561C> T of TULP1 in Family 1, Family 2 and Family 5, respectively. There were compound heterozygous mutations of RPGRIP1 c.391delG and c.1468-2A> G in Family 3 and c.715delA and c.1765C> T in Family 6, respectively. Homozygous mutation of c.3177_3178delAC of GUCY2D was found in Family 4.The parents of all six patients were carriers of corresponding heterozygous mutations. TULP1 gene c.1142T> G, RPGRIP1 gene c.391delG, c.715delA and c.1765C> T and GUCY2D gene c.3177_3178delAC mutations were novel mutations and unreported. The 381th amino acid locus of product protein of TULP1 gene was highly conserved among species. The protein prediction software predicted that the mutation pathogenic. The c.391delG, c.715delA and c.1765C> T mutations of RPGRIP1 gene and c.3177_3178delAC mutation of GUCY2D gene can lead to early translation termination of their product proteins, which are pathogenic variants. Conclusion:The pathogenic mutations of TULP1, RPGRIP1 and GUCY2D genes led to LCA 15, LCA 6 and LCA 1 in six families.

2.
Article in Chinese | WPRIM | ID: wpr-885527

ABSTRACT

Objective:To analyze the applicability and feasibility of a cell-free DNA barcode-enabled single-molecule test (cfBEST) in non-invasive prenatal diagnosis of phenylketonuria.Methods:This study recruited four pregnant women who were prenatally diagnosed as heterozygous carriers of hot spot mutations in the PAH gene from pedigrees with phenylketonuria at the First Affiliated Hospital of Zhengzhou University from July to September 2019. The frequency of mutations in maternal plasma cell-free DNA and the fetuses' genotypes were analyzed by cfBEST. Nested polymerase chain reaction primers were designed to amplify the mutation sites in each pedigree. The results of cfBEST were compared with those of invasive prenatal diagnosis. Descriptive analysis was used for data analysis. Results:In pedigree 1, the frequency of c.603T>G and c.842+2T>A mutations in maternal plasma cell-free DNA were 48.40% (291/601) and 9.70% (61/628), which was detected by cfBEST. The fetus was diagnosed with phenylketonuria with two heterozygous mutations. In pedigree 2, the frequency of c.1238G>C and c.842+2T>A mutations in maternal plasma cell-free DNA was 43.70% (786/1 798) and 0% (0/1 550), respectively. Both mutations were wild-type, and the fetus was neither phenylketonuria nor a carrier. In pedigree 3, the frequency of c.1045T>G and c.728G>A mutations in maternal plasma cell-free DNA was 44.00% (930/2 112) and 0% (0/705), respectively, suggesting that both mutations in the fetus were wild-type, and the fetus was neither phenylketonuria nor a carrier. In pedigree 4, the frequency of c.755G>A and c.728G>A mutations were 45.40% (743/1 637) and 4.50% (28/849), respectively, which indicated that the former was wild-type, and the latter was heterozygous; namely the fetus was a carrier of phenylketonuria. The results of cfBEST were consistent with those of invasive prenatal diagnosis. Three pedigrees (Pedigree 2, 3 and 4) continued the pregnancy to full-term, and the phenylalanine levels in the neonates were all below 120 μmol/L. No abnormalities were reported in those three infants during follow-ups at one, three, and six months after birth.Conclusions:The cfBEST could be used for non-invasive prenatal diagnosis of phenylketonuria caused by PAH gene mutation, but further studies with a larger sample size are needed.

3.
Article in Chinese | WPRIM | ID: wpr-885513

ABSTRACT

Objective:To analyze the genetic test results and ultrasonographic markers of 41 fetuses with short femurs and their relationship.Methods:This study retrospectively analyzed 41 fetuses who were diagnosed with short femurs by ultrasound during 19-37 gestational weeks and underwent prenatal genetic examination at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2019. According to the results of genetic examination, these cases were divided into three groups after excluding three cases of variants of unknown significance: genetically normal group, chromosome variation (including chromosomal aneuploidy and pathogenic or likely pathogenic copy number variations) group, and gene mutation (including pathogenic or likely pathogenic gene mutations) group. According to the head circumference (HC), abdominal circumference (AC) and femur length (FL), Z FL, FL/HC, FL/AC, ΔZ H-F and ΔZ H+A-2F for each fetus were calculated. One-way ANOVA and LSD- t test were used for statistical analysis. Results:(1) Among the 41 fetuses with short femurs, there were 28 in the genetically normal group, five in the chromosome variation group, three with chromosome variations of unknown significance and five in the gene mutation group. (2) In the genetically normal, chromosome variation and gene mutation groups, Z FL values were -2.78±0.77, -4.36±0.69 and -4.69±0.70; FL/HC ratios were 0.178±0.011, 0.170±0.010 and 0.131±0.022; FL/AC ratios were 0.197±0.013, 0.186±0.011 and 0.151±0.017; ΔZ H-F values were 2.49±1.09, 3.53±1.28 and 8.17±1.30; ΔZ H+A-2F values were 4.44±2.00, 6.78±2.20 and 14.28±1.26, respectively. The differences in Z FL values between the genetically normal group and the chromosome variation group as well as the gene mutation group were statistically significant (both P<0.05); so were the differences in FL/HC, FL/AC and ΔZ H-F values between the gene mutation group and the genetically normal group as well as the chromosome variation group (all P<0.05) and in any pairwise comparison of ΔZ H+A-2F among the three groups (all P<0.05). Conclusions:The genetic etiology of fetal short femurs is mainly related to chromosomal variations (including chromosomal aneuploidy and pathogenic or likely pathogenic copy number variations) and gene mutation. In fetuses with chromosome variation and gene mutation, the degree of the femoral development delay relative to the development of HC and AC is worse than that in the normal genetic results group.

4.
Article in Chinese | WPRIM | ID: wpr-885098

ABSTRACT

Turnner syndrome is a common sex chromosome disorder. We reported a rare case with Turnner syndrome caused by abnormal number and structure of sex chromosomes. Hereby fluorescence in situ hybridization (FISH) and copy number variation by whole genome low depth sequencing (CNV-seq) were used to clarify the abnormal chromosome. This study provides a diagnostic strategy for clinicians and genetic researchers.

5.
Article in Chinese | WPRIM | ID: wpr-879617

ABSTRACT

OBJECTIVE@#To detect gene inversion in two pedigrees affected with Hemophilia A by using Nanopore sequencing technology.@*METHODS@#Peripheral blood samples were taken from members of the two pedigrees. Following extraction of genome DNA, genetic variants of the carriers were detected by Nanopore sequencing and subjected to bioinformatic analysis.@*RESULTS@#Nanopore sequencing has identified the niece of the proband of the pedigree 1 as carrier of Hemophilia A Inv22, and the mother of the proband of the pedigree 2 as carrier of Hemophilia A Inv1, which was consistent with clinical findings. Breakpoint sites in both pedigrees were accurately mapped. Statistical analysis of the sequencing results revealed a large number of variations in the carriers' genomes including deletions, duplications, insertions, inversions and translocations.@*CONCLUSION@#Nanopore sequencing can be used to analyze gene inversions associated with Hemophilia A, which also provided a powerful tool for the diagnosis of diseases caused by gene inversions.


Subject(s)
Chromosome Inversion/genetics , Hemophilia A/genetics , Humans , Introns , Nanopore Sequencing , Pedigree
6.
Article in Chinese | WPRIM | ID: wpr-879605

ABSTRACT

OBJECTIVE@#To explore the clinical and genetic characteristics of a child with X-linked hypohidrotic ectodermal dysplasia (XLHED).@*METHODS@#Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents with informed consent and subjected to copy number variation (CNV) analysis and whole exome sequencing (WES).@*RESULTS@#The male infant manifested sparse hair, anhidrosis, anuresis due to polycystic kidney dysplasia, external genital malformation and anal atresia. WES has revealed a 406 bp hemizygous deletion at Xq13 (68 836 147-68 836 553) in the proband, which encompassed exon 1 of the EDA gene. A heterozygous deletion at the same site was detected in the mother, while no deletion or duplication of the site was detected in the father.@*CONCLUSION@#The hemizygous deletion of EDA gene exon 1 probably underlay the ectodermal dysplasia in the proband. Above result has provided a basis for genetic counseling and prenatal diagnosis for the family.


Subject(s)
Child , DNA Copy Number Variations , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Genetic Testing , Humans , Infant , Male , Pedigree
7.
Article in Chinese | WPRIM | ID: wpr-879603

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with X-linked hereditary Alport syndrome.@*METHODS@#Next generation sequencing was carried out for the pedigree. Candidate variant was validated by Sanger sequencing. Pathological changes of renal basement membrane and expression of COL4A5 protein were analyzed by renal biopsy and immunofluorescence assay, respectively.@*RESULTS@#All patients from the pedigree manifested progressive renal damage, gross hematuria, proteinuria and nephrotic syndrome. Renal biopsy of the proband revealed thickening of the basement membrane. No expression of the COL4A5 gene was detected by immunofluorescence. High-throughput sequencing and Sanger sequencing indicated that the proband has carried a c.3706delC (p.1236Pfs*69) variant in exon 41 of the COL4A5 gene. The same variant was also found in his mother and two brothers whom were similarly affected.@*CONCLUSION@#The novel c.3706delC (p.1236Pfs*69) variant of the COL4A5 gene probably underlay the pathogenesis of X-linked hereditary Alport syndrome in this pedigree. Above findings have enriched the spectrum of COL4A5 gene variants and provided a basis for the diagnosis and genetic counseling for the pedigree.


Subject(s)
Collagen Type IV/genetics , Hematuria , High-Throughput Nucleotide Sequencing , Humans , Male , Mutation , Nephritis, Hereditary/genetics , Pedigree
8.
Article in Chinese | WPRIM | ID: wpr-879599

ABSTRACT

OBJECTIVE@#To explore the genetic basis for two Chinese pedigrees affected with Huntington disease and provide prenatal diagnosis for them.@*METHODS@#Peripheral venous blood samples were collected from the probands. PCR and capillary gel electrophoresis were used to determine the number of CAG repeats in their IT15 gene. Pre-symptomatic testing was offered to their children and relatives, and prenatal diagnosis was provided to three pregnant women from the two pedigrees.@*RESULTS@#The two probands, in addition with three asymptomatic members, were found to have a (CAG)n repeat number greater than 40. Upon prenatal diagnosis, the numbers of CAG repeats in two fetuses from pedigree 1 were determined as (16, 19) and (18, 19), both were within the normal range. A fetus from pedigree 2 was found to have a CAG repeat number of (15, 41), which exceeded the normal range.@*CONCLUSION@#Genetic testing can facilitate the diagnosis of Huntington disease and avoid further birth of affected children.


Subject(s)
Child , Female , Genetic Testing , Humans , Huntington Disease/genetics , Nerve Tissue Proteins/genetics , Pedigree , Pregnancy , Prenatal Diagnosis
9.
Article in Chinese | WPRIM | ID: wpr-879597

ABSTRACT

OBJECTIVE@#To carry out genetic testing and prenatal diagnosis for 29 Chinese pedigrees affected with tuberous sclerosis complex (TSC) and assess efficacy of combined next generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) for the diagnosis.@*METHODS@#NGS and MLPA were used in conjunct to detect variants of TSC1 and TSC2 genes among the probands of the pedigrees. Paternity test was carried out to exclude maternal DNA contamination. Prenatal diagnosis was provided to 14 couples based on the discoveries in the probands.@*RESULTS@#Twenty-seven variants were identified in the TSC1 and TSC2 genes among the 29 pedigrees, which yielded a detection rate of 93.1%. Respectively, 5 (18.5%) and 22 (81.5%) variants were identified in the TSC1 and TSC2 genes. Twelve variants were unreported previously. Prenatal diagnosis showed that five fetuses were affected with TSC, whilst the remaining nine were unaffected.@*CONCLUSION@#Above finding has expanded the spectrum of TSC1 and TSC2 gene variants. Combined NGS and MLPA has enabled diagnosis of TSC with efficiency and accuracy.


Subject(s)
DNA Mutational Analysis , Female , Genetic Testing , Humans , Mutation , Pregnancy , Prenatal Diagnosis , Tuberous Sclerosis/genetics , Tuberous Sclerosis Complex 1 Protein/genetics , Tuberous Sclerosis Complex 2 Protein/genetics
10.
Article in Chinese | WPRIM | ID: wpr-879595

ABSTRACT

OBJECTIVE@#To summarize the result of genetic testing and therapeutic prospect of 2042 unrelated Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD) from a single center from 2005 to 2019.@*METHODS@#Peripheral blood samples of the pedigrees were collected for the detection of DMD gene variants with combined multiple ligation-dependent probe amplification (MLPA), next generation sequencing (NGS) and Sanger sequencing.@*RESULTS@#DMD and BMD have respectively accounted for 78.60% and 21.40% of the pedigrees, which included 33 female probands. Variants of the DMD gene were detected in 1986 pedigrees (97.26%). Large deletions, duplications and small-scale mutations have respectively accounted for 71.85%, 8.76% and 19.39%. Common deletions and duplications have included deletion of exons 45-50 and duplications of exon 2, while no hot spot was found with small-scale mutations. For 1595 pedigrees affected with DMD, 935 (58.62%) were hereditary and 660 (41.38%) were de novo in origin. 34.28% (700/2042) of the patients had symptoms which could be relieved by gene therapy.@*CONCLUSION@#This has been the largest single-center study of DMD pedigrees, which has attained definite diagnosis in 97.26% of the patients. The results have enabled genetic counseling and prenatal diagnosis for the affected families upon their subsequent pregnancies, enriched the spectrum of DMD gene variants, as well as facilitated study of the mechanism of DMD gene mutations and exploration of clinical treatment.


Subject(s)
China , Dystrophin/genetics , Exons/genetics , Female , Gene Deletion , Genetic Testing , Humans , Muscular Dystrophy, Duchenne/therapy , Mutation , Pedigree , Pregnancy
11.
Article in Chinese | WPRIM | ID: wpr-879589

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a neonate with Pierre-Robin sequence.@*METHODS@#The child was subjected to chromosomal karyotyping, single nucleotide polymorphism array (SNP-array)-based comparative genomic hybridization and fluorescence in situ hybridization (FISH) analysis.@*RESULTS@#The child has featured microgthnia, glossoptosis, upper airway obstruction, mandible dehiscence and short neck. He was found to have a karyotype of 46,XY,der(4)add(4)(q34). Her mother's karyotype was determined as 46,XX,t(1;4)(q43;q34), while his father was 46,XY. SNP-array analysis suggested the child to be arr [hg19] 1q42.2q44 (232 527 958-249 202 755)× 3; 4q34.3q35.2 (168 236 901-190 880 409)× 1. The result of SNP-array for both parents was normal. FISH analysis confirmed that his mother has carried a balanced t(1;4)(q42;34) translocation. The aberrant chromosome 4 in the child has derived from his mother's translocation, which gave rise to partial 1q trisomy and 4q monosomy.@*CONCLUSION@#The 1q42.2q44 duplication and 4q34.3q35.2 deletion of the child probably underlay his abnormal phenotype of Pierre-Robin sequence.


Subject(s)
Child , Comparative Genomic Hybridization , Female , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Male , Monosomy , Pierre Robin Syndrome/genetics , Translocation, Genetic , Trisomy/genetics
12.
Article in Chinese | WPRIM | ID: wpr-879588

ABSTRACT

OBJECTIVE@#To describe the clinical and genetic characteristics of a child with 14q12q13.1 deletion involving the FOXG1 gene.@*METHODS@#Clinical manifestation of the child was analyzed. Peripheral blood sample of the patient was subjected to chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) analysis.@*RESULTS@#The male infant has developed feeding difficulty, poor sucking, lower limb tremor, and frontal bruising 8 days after birth. Magnetic resonance imaging revealed significant enlargement of bilateral ventricles and corpus callosum dysplasia. Chromosomal analysis revealed a karyotype of 46,XY,del(14)(q12q13.1), and SNP-array confirmed that there was a 9.6 Mb deletion in 14q11.2q13.1, which encompassed the FOXG1 gene.@*CONCLUSION@#For patients with brain development abnormalities, dyskinesia, cognitive impairment, speech disorder and other manifestations, copy number variation of the FOXG1 gene should be excluded. SNP-array should be carried out as early as possible to attain the diagnosis.


Subject(s)
Child , Chromosome Deletion , DNA Copy Number Variations , Forkhead Transcription Factors/genetics , Heterozygote , Humans , Infant , Karyotyping , Male , Nerve Tissue Proteins/genetics , Polymorphism, Single Nucleotide
13.
Article in Chinese | WPRIM | ID: wpr-879576

ABSTRACT

OBJECTIVE@#To assess the value of non-invasive prenatal testing based on cfDNA barcode-enabled single-molecule test (cfBEST) for the prenatal diagnosis of oculocutaneous albinism type I in a family.@*METHODS@#Prenatal genetic diagnosis was carried out by using the cfBEST-based method as well as invasive prenatal diagnosis through amniocentesis. The outcome of the pregnancy was followed up.@*RESULTS@#Non-invasive prenatal testing based on cfBEST showed a fetal DNA concentration of 6.6%, with the proportion of c.929_930insC (p.Arg311Lysfs*7) and c.1037-7T>A mutations being 45.7% and 0%, respectively. The posterior frequency of the negative results was 1, suggesting that the fetus carried neither of the two mutations. The result was consistent with that of invasive prenatal diagnosis, and the follow-up found that the fetus was normal.@*CONCLUSION@#Non-invasive prenatal testing based on cfBEST can be used to detect maternal and fetal genotypes in maternal cell-free DNA, which is clinically feasible.


Subject(s)
Albinism , Albinism, Oculocutaneous/genetics , Amniocentesis , Cell-Free Nucleic Acids , Female , Humans , Pregnancy , Prenatal Diagnosis
14.
Article in Chinese | WPRIM | ID: wpr-879575

ABSTRACT

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the detection of fetal chromosomal aneuploidies in women with twin pregnancy.@*METHODS@#A total of 2473 women with twin pregnancy underwent the NIPT test to assess the risk for fetal chromosomal aneuploidies from January 2016 to September 2019. Those with a high risk by NIPT were confirmed by amniocentesis or chorionic villus sampling. All cases were followed up to evaluate the positive prediction value of NIPT for twin pregnancies.@*RESULTS@#Among the 2473 women, the NIPT test has identified 31 cases (1.25%) with a high risk for fetal chromosomal aneuploidies, which included 5 cases of trisomy 21, 1 case of chromosome 21 deletion, 4 cases of trisomy 18, 7 cases of sex chromosome abnormality and 14 cases of microdeletion and microduplication. By invasive prenatal diagnosis or chromosomal karyotyping analysis of neonates, 5 cases of trisomy 21, 3 cases of trisomy 18, 1 case of sex chromosome abnormality, and 2 cases of microdeletion and microduplication were confirmed, which yielded a positive predictive value of 100%, 75%, 25% and 25%, respectively.@*CONCLUSION@#NIPT can be used for the screening of fetal chromosomal aneuploidies in women with twin pregnancy with high accuracy. The method is non-invasive, safe and effective for the screening of fetal chromosomal aneuploidies, in particular trisomy 21.


Subject(s)
Aneuploidy , Chromosome Disorders , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy, Twin , Prenatal Diagnosis , Trisomy , Trisomy 13 Syndrome , Trisomy 18 Syndrome
15.
Article in Chinese | WPRIM | ID: wpr-879570

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child affected with Bainbridge-Ropers syndrome.@*METHODS@#Genomic DNA was extracted from peripheral venous blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out to detect genetic variant of the proband. Candidate variant was verified by Sanger sequencing.@*RESULTS@#The 3-year-old boy presented with psychomotor retardation, linguistic difficulties, mental retardation and peculiar craniofacial phenotype. A de novo heterozygous nonsense variant of the ASXL3 gene, c.3106C>T, was identified by WES in the proband, and the same mutation was not found among his parents. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.3106C>T variant was predicted to be pathogenic (PVS1+PS2+PP4).@*CONCLUSION@#The heterozygous variant c.3106C>T of the ASXL3 gene probably underlies the Bainbridge-Ropers syndrome in the patient. Above result has enabled the clinical diagnosis and genetic counseling for the family.


Subject(s)
Child , Child, Preschool , Heterozygote , Humans , Intellectual Disability/genetics , Male , Mutation , Phenotype , Transcription Factors/genetics , Whole Exome Sequencing
16.
Article in Chinese | WPRIM | ID: wpr-879554

ABSTRACT

OBJECTIVE@#To analyze the clinical phenotype and genetic variants in five Chinese pedigrees affected with Dysferlinopathy.@*METHODS@#Next generation sequencing (NGS) was carried out for the probands from the five pedigrees. Suspected variants were validated by Sanger sequencing. Pathogenicity of the variants was assessed based on the standards and guidelines by the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#Ten DYSF gene variants (including 5 frameshift variants, 3 splicing variants, 1 missense variant and 1 nonsense variant) were detected. Among these, c.1375dupA (p.Met459Asnfs*15), c.610C>T (p.Arg204X), c.1180+5G>A and c.1284+2T>C were known to be pathogenic, while c.4008_4010delCCTinsAC (p.Leu1337Argfs*8), c.1137_1169del (p.379_390del), c.754A>G(p.Thr252Ala), c.1175_1176insGCAGAGTG (p.Met394Serfs*7), c.3114_3115insCGGC (p.Arg1040Profs*74) and c.1053+3G>C were unreported previously. Of the six novel variants, c.1137_1169del, c.1175_1176insGCAGAGTG and c.3114_3115insCGGC were predicted as pathogenic (PVS1+PM2+PM3), c.4008_4010delCCTinsAC as likely pathogenic (PVS1+PM2), c.754A>G and c.1053+3G>C as variants of uncertain significance based on the ACMG standards and guidelines.@*CONCLUSION@#Variants of the DYSF gene probably underlay Dysferlinopathy in the patients among the five pedigrees. Above finding has enriched the spectrum of DYSF gene variants.


Subject(s)
Humans , Muscular Dystrophies, Limb-Girdle/genetics , Mutation , Pedigree , Phenotype , RNA Splicing
17.
Article in Chinese | WPRIM | ID: wpr-879526

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a fetus with lissencephaly.@*METHODS@#Genomic DNA was extracted from amniotic fluid sample and subjected to copy number variation (CNV) analysis.@*RESULTS@#The fetus was found to harbor a heterozygous 5.2 Mb deletion at 17p13.3p13.2, which encompassed the whole critical region of Miller-Dieker syndrome (MDS) (chr17: 1-2 588 909).@*CONCLUSION@#The fetus was diagnosed with MDS. Deletion of the PAFAH1B1 gene may account for the lissencephaly found in the fetus.


Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics , Chromosome Deletion , Chromosomes, Human, Pair 17/genetics , Classical Lissencephalies and Subcortical Band Heterotopias/genetics , Female , Fetus , Genetic Testing , Humans , Microtubule-Associated Proteins/genetics , Pregnancy , Prenatal Diagnosis
18.
Article in Chinese | WPRIM | ID: wpr-879518

ABSTRACT

OBJECTIVE@#To explore the genetic basis of four Chinese families affected with deafness.@*METHODS@#All probands were subjected to next generation sequencing (NGS). Suspected variant were verified by Sanger sequencing among the family members. Prenatal diagnosis was provided for three couples through Sanger sequencing.@*RESULTS@#All probands were found to carry pathogenic variants of the TMC1 gene, which included c.100C>T (p.R34X) and c.642+4A>C in family 1, c.582G>A (p.W194X) and c.589G>A (p.G197R) in family 2, c.1396_1398delAAC and c.1571T>C (p.F524S) in family 3, and homozygosity of c.2050G>C (p.D684H) in family 4. All parents were heterozygous carriers of the variants. The c.642+4A>C and c.1571T>C (p.F524S) were unreported previously. Prenatal diagnosis revealed that none of the fetuses were affected. Follow-up confirmed that all newborns had normal hearing.@*CONCLUSION@#Variant of the TMC1 gene probably underlay the deafness in the four families. Above findings have enhanced our understanding of the function of the TMC1 gene and enriched its variant spectrum. The results also facilitated genetic counseling and prenatal diagnosis for the families.


Subject(s)
China , Deafness/genetics , Female , Genetic Variation , Humans , Infant, Newborn , Male , Membrane Proteins/genetics , Mutation , Pedigree , Pregnancy , Prenatal Diagnosis
19.
Article in Chinese | WPRIM | ID: wpr-781301

ABSTRACT

OBJECTIVE@#To explore the genetic basis of an infant featuring congenital cataract, developmental delay and proteinuria.@*METHODS@#Clinical data and peripheral blood samples of the family were collected. Potential variants were screened by using targeted capture and high-throughput sequencing on a NextSeq 500 platform. Suspected variant was verified by quantitative PCR. Pathogenicity of the candidate variant was predicted based on clinical presentation and laboratory tests.@*RESULTS@#The infant's phenotypes included brain development retardation and proteinuria. Cranial MRI indicated widening of cerebral fissure, bilateral frontal and temporal subarachnoid cavities, and dysplasia of white matter myelination in posterior angular of ventricle. A novel duplication of exons 5 to 16 of the OCRL gene was found in the patient. His mother has carried the same duplication variant.@*CONCLUSION@#The duplication variant of the OCRL gene probably underlies the oculo-cerebro-renal syndrome in the infant. Due to the heterogeneity of its clinical manifestation, pertinent genetic detection is essential for acurrate diagnosis of patients who have the related phenotypes.


Subject(s)
Exons , Genetics , Genetic Testing , Humans , Infant , Oculocerebrorenal Syndrome , Genetics , Phenotype , Phosphoric Monoester Hydrolases , Genetics
20.
Article in Chinese | WPRIM | ID: wpr-781299

ABSTRACT

OBJECTIVE@#To determine the frequency, common chromosomal karyotypes and breakpoints, and involved regions among carriers of reciprocal translocations from Henan Province, and to explore the influence of common breakpoint regions on pregnancy and fetal development.@*METHODS@#For 586 carriers of reciprocal translocations, the above features were retrospectively analyzed.@*RESULTS@#The 586 reciprocal translocations were identified among 62 477 subjects, which yielded a frequency of 0.94%. Among these, 572 (0.92%) had abnormal fertility, and 14 (0.02%) had a history of abnormal fetal development. Statistical analysis showed that chromosomes 1, 4, 7 and 11 were most frequently involved, with t(11;22)(q25;q13) being the most common type of translocation. In total 437 breakpoint regions were identified, with 11q23, 22q13 and 1p36 being most frequently involved, which resulted in infertility, abortion, embryo death, congenital malformation, development delay, mental retardation or a normal phenotype.@*CONCLUSION@#Above results indicated a 0.92% carrier rate for reciprocal chromosomal translocations in Henan. The location of breakpoint regions may affect the pregnancy and/or fetal development. Discovery of such regions may enable more accurate genetic, reproductive and developmental counseling for carriers, and provide reference for delineation of function and pathogenetic mechanism of the relevant genes.


Subject(s)
Chromosome Breakpoints , Female , Heterozygote , Humans , Karyotype , Karyotyping , Pregnancy , Retrospective Studies , Translocation, Genetic , Genetics
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