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1.
Journal of Southern Medical University ; (12): 1047-1050, 2023.
Article in Chinese | WPRIM | ID: wpr-987021

ABSTRACT

OBJECTIVE@#To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients.@*METHODS@#A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment.@*RESULTS@#Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05).@*CONCLUSION@#Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.


Subject(s)
Humans , Autoantibodies , Cyclosporine/therapeutic use , Glomerulonephritis, Membranous/diagnosis , Homozygote , Immunosuppressive Agents/therapeutic use , Pharmacogenomic Testing , Receptors, Phospholipase A2 , Sequence Deletion , Serum Albumin , Tacrolimus/therapeutic use
2.
Chinese Journal of Medical Genetics ; (6): 301-307, 2023.
Article in Chinese | WPRIM | ID: wpr-970923

ABSTRACT

OBJECTIVE@#To explore the genetic basis for 4 patients with globozoospermia.@*METHODS@#Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing.@*RESULTS@#All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3' UTR region.@*CONCLUSION@#DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.


Subject(s)
Male , Humans , Teratozoospermia/genetics , Homozygote , Semen , Sequence Deletion , 3' Untranslated Regions , Membrane Proteins
3.
Chinese Journal of Medical Genetics ; (6): 733-736, 2023.
Article in Chinese | WPRIM | ID: wpr-981817

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree with 6q26q27 microduplication and 15q26.3 microdeletion.@*METHODS@#A fetus with a 6q26q27 microduplication and a 15q26.3 microdeletion diagnosed at the First Affiliated Hospital of Wenzhou Medical University in January 2021 and members of its pedigree were selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were analyzed by G-banding karyotyping and chromosomal microarray analysis (CMA), and its maternal grandparents were also subjected to G-banding karyotype analysis.@*RESULTS@#Prenatal ultrasound had indicated intrauterine growth retardation of the fetus, though no karyotypic abnormality was found with the amniotic fluid sample and blood samples from its pedigree members. CMA revealed that the fetus has carried a 6.6 Mb microduplication in 6q26q27 and a 1.9 Mb microdeletion in 15q26.3, and his mother also carried a 6.49 duplication and a 1.867 deletion in the same region. No anomaly was found with its father.@*CONCLUSION@#The 6q26q27 microduplication and 15q26.3 microdeletion probably underlay the intrauterine growth retardation in this fetus.


Subject(s)
Female , Humans , Pregnancy , East Asian People , Fetal Growth Retardation/genetics , Karyotype , Pedigree , Prenatal Diagnosis , Sequence Deletion , Chromosome Duplication
4.
Chinese Journal of Medical Genetics ; (6): 655-660, 2023.
Article in Chinese | WPRIM | ID: wpr-981803

ABSTRACT

OBJECTIVE@#To carry out carrier screening for Spinal muscular atrophy (SMA) in reproductive-aged individuals from Dongguan region and determine the carrier frequency of SMN1 gene mutations.@*METHODS@#Reproductive-aged individuals who underwent SMN1 genetic screening at the Dongguan Maternal and Child Health Care Hospital from March 2020 to August 2022 were selected as the study subjects. Deletions of exon 7 and 8 (E7/E8) of the SMN1 gene were detected by real-time fluorescence quantitative PCR (qPCR), and prenatal diagnosis was provided for carrier couples by multiple ligation-dependent probe amplification (MLPA).@*RESULTS@#Among the 35 145 subjects, 635 were found to be carriers of SMN1 E7 deletion (586 with heterozygous E7/E8 deletion, 2 with heterozygous E7 deletion and homozygous E8 deletion, and 47 with sole heterozygous E7 deletion). The carrier frequency was 1.81% (635/35 145), with 1.59% (29/1 821) in males and 1.82% (606/33 324) in females. There was no significant difference between the two genders (χ² = 0.497, P = 0.481). A 29-year-old woman was found to harbor homozygous deletion of SMN1 E7/E8, and was verified to have a SMN1∶SMN2 ratio of [0∶4], none of her three family members with a [0∶4] genotype had clinical symptoms. Eleven carrier couples had accepted prenatal diagnosis, and one fetus was found to have a [0∶4] genotype, and the pregnancy was terminated.@*CONCLUSION@#This study has determined the SMA carrier frequency in Dongguan region for the first time and provided prenatal diagnosis for carrier couples. The data can provide a reference for genetic counseling and prenatal diagnosis, which has important clinical implications for the prevention and control of birth defects associated with SMA.


Subject(s)
Humans , Child , Pregnancy , Male , Female , Adult , Homozygote , Sequence Deletion , Prenatal Diagnosis , Genetic Testing , Muscular Atrophy, Spinal/genetics , Survival of Motor Neuron 1 Protein/genetics , Genetic Carrier Screening
5.
Chinese Journal of Contemporary Pediatrics ; (12): 1038-1043, 2021.
Article in English | WPRIM | ID: wpr-922388

ABSTRACT

OBJECTIVES@#To study the natural history of spinal muscular atrophy (SMA) in Chongqing and surrounding areas, China, and to provide a clinical basis for comprehensive management and gene modification therapy for SMA.@*METHODS@#A retrospective analysis was performed on the medical data and survival status of 117 children with SMA.@*RESULTS@#Of the 117 children, 62 (53.0%) had type 1 SMA, 45 (38.5%) had type 2 SMA, and 10 (8.5%) had type 3 SMA, with a median age of onset of 2 months, 10 months, and 15 months, respectively. Compared with the children with type 2 SMA or type 3 SMA, the children with type 1 SMA had significantly shorter time to onset, consultation, and confirmed diagnosis (@*CONCLUSIONS@#There are differences in clinical manifestations and survival rates among children with different types of SMA. The children with type 1 SMA have a low survival rate, and those with type 2 SMA may have non-linear regression of motor ability. Early identification and management of SMA should be performed in clinical practice.


Subject(s)
Child , Humans , Infant , Homozygote , Muscular Atrophy, Spinal/genetics , Retrospective Studies , Sequence Deletion , Spinal Muscular Atrophies of Childhood/genetics
6.
Chinese Journal of Medical Genetics ; (6): 162-165, 2021.
Article in Chinese | WPRIM | ID: wpr-879546

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child featuring unexplained rapid growth and heart malformation.@*METHODS@#Whole exome sequencing (WES)was carried out for the patient. Suspected variant was verified by Sanger sequencing and subjected to bioinformatic analysis.@*RESULTS@#The child was found to harbor a novel de novo c.5846_5848delATA (p. N1949del) variant in exon 48 of the FBN1 gene, which was predicted to be pathogenic by Mutation Taster. The patient was ultimately diagnosed with Marfan syndrome.@*CONCLUSION@#Above finding has enriched the spectrum of genetic variants associated with Marfan syndrome. WES has provided a powerful tool for the diagnosis of rare diseases.


Subject(s)
Child , Humans , Exons , Fibrillin-1/genetics , Heart Defects, Congenital , Marfan Syndrome/genetics , Mutation , Sequence Deletion , Exome Sequencing
7.
Chinese Journal of Medical Genetics ; (6): 1387-1390, 2020.
Article in Chinese | WPRIM | ID: wpr-879506

ABSTRACT

OBJECTIVE@#To carry out prenatal diagnose for a fetus with ultrasonography abnormalities using multiple genetic techniques.@*METHODS@#Routine G-banding chromosomal analysis and single nucleotide polymorphism array (SNP-array) were applied in conjunction for the prenatal diagnosis of the fetus. The result was confirmed by fluorescence in situ hybridization (FISH).@*RESULTS@#SNP-array detected that the fetus has carried a hemizygous 5.1 Mb deletion at 22q13.31q13.33, which is associated with Phelan-McDermid syndrome, and a hemizygous 4.5 Mb deletion at 21q21.1q21.2. FISH analysis of the fetus and its parents suggested that both deletions were de novo in origin.@*CONCLUSION@#The hemizygous deletions on 21q21.1q21.2 and 22q13.31q13.33 probably underlay the abnormal phenotype of the fetus. Genetic analysis can provide crucial information for the prenatal diagnosis and genetic counseling.


Subject(s)
Female , Humans , Male , Pregnancy , Chromosome Deletion , Chromosome Disorders/genetics , Chromosomes, Human, Pair 21/genetics , Chromosomes, Human, Pair 22/genetics , Fetus , In Situ Hybridization, Fluorescence , Polymorphism, Single Nucleotide , Prenatal Diagnosis , Sequence Deletion/genetics
8.
Chinese Journal of Medical Genetics ; (6): 1371-1375, 2020.
Article in Chinese | WPRIM | ID: wpr-879502

ABSTRACT

OBJECTIVE@#To explore the genetic basis for an infant with neonatal diabetes (NDM) and multiple malformations.@*METHODS@#Genetic variants were detected by next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing.@*RESULTS@#A de novo heterozygous variant, c.1454_1455del(p.K485Rfs), was detected in exon 5 of the GATA6 gene. The variant was undetected in his parents and unreported previously. Bioinformatic analysis predicted the variant to be pathogenic.@*CONCLUSION@#The heterozygous variant of c.1454_1455del(p.K485Rfs) of the GATA6 gene probably underlies the disease in this child. Genetic testing can facilitate diagnosis and genetic counseling for NDM.


Subject(s)
Adult , Female , Humans , Infant, Newborn , Male , Abnormalities, Multiple , Diabetes Mellitus/genetics , Genetic Testing , Heterozygote , High-Throughput Nucleotide Sequencing , Sequence Deletion/genetics
9.
Chinese Journal of Medical Genetics ; (6): 1265-1268, 2020.
Article in Chinese | WPRIM | ID: wpr-879482

ABSTRACT

OBJECTIVE@#To explore the genetic cause of a patient suspected for congenital ectodermal dysplasia with repeated hyperthermia and to assess the reproductive risk for his family.@*METHODS@#Medical whole-exome sequencing (WES) were used to detect single-nucleotide variations and low-coverage massively parallel copy number variation sequencing (CNV-seq) were employed to verify suspected CNVs. PCR and real-time quantitative PCR were applied to confirm the deletion of EDA gene.@*RESULTS@#The results of WES suggested that the patient carried a hemizygous deletion for chrX:69 243 016-69 395 730. CNV-seq indicated that the patient carried a deletion of approximately 0.12 Mb on Xq13.1, which encompassed the EDA gene. The PCR results confirmed that there was a hemizygous deletion of exons 3 to 8 of the EDA gene. The same deletion was not found in his mother.@*CONCLUSION@#The congenital ectodermal dysplasia of the patient may be attributed to deletion of exons 3 to 8 of the EDA gene, which could be de novo or derive from germline mosaicism of his mother. The WES and CNV-seq are of great value for the diagnosis of rare diseases.


Subject(s)
Humans , DNA Copy Number Variations , Ectodermal Dysplasia/genetics , Ectodysplasins/genetics , Exons , Genetic Testing , High-Throughput Nucleotide Sequencing , Mosaicism , Sequence Deletion , Exome Sequencing
10.
Chinese Journal of Medical Genetics ; (6): 547-550, 2020.
Article in Chinese | WPRIM | ID: wpr-826536

ABSTRACT

OBJECTIVE@#To analyze the clinical features and pathogenesis of a fetus with holoprosencephaly.@*METHODS@#The findings of prenatal ultrasonography was reviewed. Following elective abortion, whole exome sequencing (WES) was carried out to identify potential pathogenic variant. Copy number variants (CNVs) of the abortus and its parents were detected by low-depth high-throughput sequencing. The parents were also analyzed by chromosomal karyotyping.@*RESULTS@#Prenatal ultrasound suggested that the fetus had holoprosencephaly. WES revealed that it had approximately 33 Mb deletion at chromosome 13 involving ZIC2, a haploid dose sensitive gene. The results of low-depth high-throughput sequencing confirmed that the fetus carried a de novo 32.32 Mb deletion at 13q31.1-34. Karyotyping analysis has excluded gross chromosomal aberration in both parents.@*CONCLUSION@#The fetus was diagnosed with holoprosencephaly, which may be attributable to the 13q31.1-34 deletion involving the ZIC2 gene.


Subject(s)
Adult , Female , Humans , Male , Pregnancy , Chromosomes, Human, Pair 13 , Genetics , Fetus , Genetic Testing , Holoprosencephaly , Diagnostic Imaging , Genetics , Pathology , Karyotyping , Nuclear Proteins , Genetics , Prenatal Diagnosis , Sequence Deletion , Transcription Factors , Genetics , Ultrasonography, Prenatal , Exome Sequencing
11.
Chinese Journal of Medical Genetics ; (6): 559-562, 2020.
Article in Chinese | WPRIM | ID: wpr-826533

ABSTRACT

OBJECTIVE@#To carry out genetic analysis for a family with a fetus manifesting bilateral polycystic renal dysplasia and oligohydramnios at 16 gestational week and a previous history for fetal renal anomaly.@*METHODS@#Ultrasound scan was carried out to detect the morphological changes. Following genetic counselling, the parents had decided to terminate the pregnancy. Fetal kidneys were subjected to histological examination. Target capture and next generation sequencing (NGS) was applied to the abortus to detect potential variants. The results were verified by Sanger sequencing.@*RESULTS@#Histological examination of fetal kidneys revealed cystic changes without cortex, medulla or normal renal structure. NGS has identified a heterozygous c.100+1G>A variant and deletion of exon 3 of the INVS gene, which were respectively inherited from the mother and father.@*CONCLUSION@#Through NGS and Sanger sequencing, the fetus was diagnosed with type II nephronophthisis (NPHP2). Above result can provide guidance for further pregnancy and enforce understanding of clinical features and genetic etiologies for NPHP.


Subject(s)
Female , Humans , Pregnancy , Fetus , Genetic Testing , Heterozygote , Mutation , Polycystic Kidney, Autosomal Dominant , Diagnostic Imaging , Genetics , Sequence Deletion , Genetics , Transcription Factors , Genetics , Ultrasonography
12.
Chinese Journal of Medical Genetics ; (6): 491-494, 2019.
Article in Chinese | WPRIM | ID: wpr-771982

ABSTRACT

OBJECTIVE@#To provide genetic testing for two brothers with mental retardation and epilepsy.@*METHODS@#Array comparative genomic hybridization (aCGH) was used to detect copy number variations in the two patients, their parents and maternal grandparents. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was utilized to delineate the deleted region in the pedigree.@*RESULTS@#A 138 kb deletion in 15q11.2 region was detected by aCGH in both patients, which encompassed part of the UBE3A gene. MS-MLPA has narrowed down the region to exons 8 to 14 of the UBE3A gene. The same deletion was also found in their mother and grandfather.@*CONCLUSION@#The pathogenesis of this rare form of recurrent Angelman syndrome may be attributed to the partial deletion of maternal UBE3A gene.


Subject(s)
Female , Humans , Male , Angelman Syndrome , Comparative Genomic Hybridization , DNA Copy Number Variations , Gene Deletion , Sequence Deletion , Ubiquitin-Protein Ligases
13.
Chinese Journal of Medical Genetics ; (6): 581-583, 2019.
Article in Chinese | WPRIM | ID: wpr-771964

ABSTRACT

OBJECTIVE@#To detect pathogenic variation in a pedigree affected with hereditary spastic paraplegia type 31 and explore its molecular pathogenesis.@*METHODS@#Customized Roche NimbleGen capture probes were used to capture all exons of the target genes in relation with hereditary spastic paraplegia. The DNA samples were also assayed with fluorescent quantitative PCR as well as chromosomal microarray analysis using CytoScan HD chip.@*RESULTS@#The proband and her father and grandfather were found to carry a deletion for position 85 992 693-86 842 693 on chromosome 2, which spanned approximately 900 kb and encompassed the REEP1 gene. The latter has been specifically associated with hereditary spastic paraplegia type 31. The same deletion was not found in her mother who is phenotypically normal.@*CONCLUSION@#The deletional variation of the REEP1 gene probably underlies the disease in this pedigree.


Subject(s)
Female , Humans , Membrane Transport Proteins , Paraplegia , Pedigree , Sequence Deletion , Spastic Paraplegia, Hereditary , Genetics
14.
Journal of Experimental Hematology ; (6): 504-508, 2019.
Article in Chinese | WPRIM | ID: wpr-771929

ABSTRACT

OBJECTIVE@#To explore the potential pathogenetic mutations of primary hypereosinophilia(HEN)by sequencing FGFR1 FLT3, MPL and JAK2 genes, and to clarify their effect on clinical manifestation and prognosis of HEN patients.@*METHODS@#The direct DNA sequencing was employed to detect the gene mutations of FGFR1, FLT3, MPL and JAK2 in HEN patients.@*RESULTS@#One deletion mutation (2654_2753del) within tyrosine kinase domain of FLT3 gene was found in a patient suffered from severe symptoms and ended with dismal outcome, which induced a premature stop codon (G885fsX888). For FGFR1, a new variation described as 1014_1019del AACAGT for nucleotide change was found in 19 cases, resulting in T339_V340del at the protein level.@*CONCLUSION@#The deletion of 6 bases in the FGFR1 gene (1014_1019del AACAGT) is first reported as non-synonymous SNP (nsSNP) site in the patients with primary hypereosinophilia. Deletion mutations in the FLT3 gene may be related with malignant clinical features and poor prognosis.


Subject(s)
Humans , Base Sequence , Hypereosinophilic Syndrome , Genetics , Mutation , Receptors, Thrombopoietin , Sequence Deletion , fms-Like Tyrosine Kinase 3
15.
Chinese Journal of Biotechnology ; (12): 458-471, 2019.
Article in Chinese | WPRIM | ID: wpr-771361

ABSTRACT

Few tools of gene editing have been developed in Bacillus licheniformis at present. In order to enrich the tools, an FLP/FRT gene editing system that can repeatedly use a single selectable marker was constructed in Bacillus licheniformis, and the system was verified by knocking out an alpha amylase gene (amyL), an protease gene (aprE) and knocking in an exogenous Vitreoscilla hemoglobin gene (vgb). First, knock-out plasmids pNZTT-AFKF of amyL and pNZTT-EFKF of aprE were constructed using thermosensitive plasmid pNZT1 as a carrier. The two knock-out plasmids contained respective homology arms, resistance genes and FRT sites. Then the knock-out plasmids were transformed into Bacillus licheniformis and the target genes were replaced by respective deletion cassette via twice homologous exchange. Finally, an expression plasmid containing FLP recombinase reading frane was introduced and mediated the excision of resistance marker. In order to expand the practicability of the system, knock-in plasmid pNZTK-PFTF-vgb was constructed, with which knock-in of vgb at pflB site was carried out successfully. The results showed that amyL and aprE were successfully knocked out and the marker kanamycin cassette exactly excised. The activities of amylase and protease of deletion mutants were reduced by 95.3% and 80.4% respectively. vgb was successfully knocked in at pflB site and the marker tetracycline cassette excised. The expression of integrated vgb was verified via real-time PCR. It is the first time to construct an FLP/FRT system for gene editing in Bacillus licheniformis, which could provide an effective technical means for genetic modification.


Subject(s)
Bacillus licheniformis , Gene Editing , Plasmids , Sequence Deletion
16.
Chinese Journal of Medical Genetics ; (6): 701-703, 2019.
Article in Chinese | WPRIM | ID: wpr-776826

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a pedigree affected with Bartter's syndrome (BS).@*METHODS@#Panel-based next-generation sequencing (NGS) was carried out to detect mutation in BS-related genes SLC12A1, KCNJ1, BSND and CLCNKB. Sanger sequencing of MAGED2 gene and chromosomal microarray analysis (CMA) were also performed on the patient. Suspected mutation was validated in her family members.@*RESULTS@#No pathogenic mutation was detected by NGS, while a 0.152 Mb microdeletion at Xp11.21 (54 834 585-54 986 301) was found in the male fetus, which removed the entire coding region of the MAGED2 gene. His mother was a heterozygous carrier of the deletion. His father and sister did not carry the same deletion.@*CONCLUSION@#The loss of the MAGED2 gene may underlie the BS in this pedigree.


Subject(s)
Female , Humans , Male , Adaptor Proteins, Signal Transducing , Genetics , Antigens, Neoplasm , Genetics , Bartter Syndrome , Genetics , Genetic Testing , Heterozygote , Mutation , Pedigree , Sequence Deletion
17.
Chinese Journal of Medical Genetics ; (6): 704-707, 2019.
Article in Chinese | WPRIM | ID: wpr-776825

ABSTRACT

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 Deletion
18.
Chinese Journal of Medical Genetics ; (6): 708-711, 2019.
Article in Chinese | WPRIM | ID: wpr-776824

ABSTRACT

OBJECTIVE@#To correlate genotype with clinical phenotype of a child featuring multiple congenital malformations.@*METHODS@#Clinical examination of the patient was carried out. Chromosome microarray analysis (CMA) was employed to detect genomic copy number variations (CNVs), and quantitative PCR (qPCR) was used for verifying the result.@*RESULTS@#The child had congenital heart disease (ventricular septal defect, atrial septal defect, pulmonary arterial hypertension, and tricuspid regurgitation), psychomotor retardation, agenesis of corpus callosum, hypospadias and scoliosis. CMA has detected a 1.8 Mb deletion at 7p22.3, a 1.8 Mb duplication at 7p22.3p22.2 and a 23.5 Mb duplication at 7q33q36.3 in the fetus, all of which were de novo in origin.@*CONCLUSION@#CMA can precisely detect microdeletion/duplications and facilitate the genotype-phenotype correlation analysis.


Subject(s)
Child , Humans , Male , Abnormalities, Multiple , Genetics , Chromosomes, Human, Pair 7 , Genetics , DNA Copy Number Variations , Genetic Testing , Heart Defects, Congenital , Genetics , Phenotype , Sequence Deletion
19.
Chinese Journal of Medical Genetics ; (6): 798-800, 2019.
Article in Chinese | WPRIM | ID: wpr-776803

ABSTRACT

OBJECTIVE@#To identify potential mutations of the CLS gene in a Chinese pedigree affected with Coffin-Lowry syndrome.@*METHODS@#Whole exome sequencing was applied to detect potential mutation in the proband, and the result was verified by Sanger sequencing.@*RESULTS@#The proband was found to carry a c.966_967delAA (p.Arg323Thr fs*11) deletional mutation in the RPS6KA3 gene. The same mutation was also found in his mother.@*CONCLUSION@#The c.966_967delAA (p.Arg323Thr fs*11) deletional mutation of the RPS6KA3 gene probably underlies the disorder in this pedigree.


Subject(s)
Humans , Asian People , China , Coffin-Lowry Syndrome , Genetics , Mutation , Pedigree , Ribosomal Protein S6 Kinases, 90-kDa , Genetics , Sequence Deletion
20.
Chinese Journal of Medical Genetics ; (6): 1175-1178, 2019.
Article in Chinese | WPRIM | ID: wpr-781323

ABSTRACT

OBJECTIVE@#To explore the feasibility of high performance liquid chromatography (DHPLC) combined with multiple ligation-dependent probe amplification (MLPA) for the prenatal diagnosis of spinal muscular atrophy (SMA).@*METHODS@#Three families who had given birth to children with SMA type I were subjected to prenatal diagnosis. Peripheral blood samples were collected from the three couples, and 10 mL amniotic fluid was taken for each fetus through amniocentesis at 16-24 gestational week. Following DNA extraction, maternal contamination was excluded by STR analysis. Copy numbers of the SMN genes were detected by denaturing high performance liquid chromatography (DHPLC). Relative copy number of SMN1, SMN2 and reference genes was detected with a MLPA P021 assay kit.@*RESULTS@#The three couples were all found to harbor heterozygous deletion of exon 7 of the SMN1 gene by DHPLC. MLPA analysis also suggested that the three couples were all carriers of SMA mutations. The fetus of family 1 harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus had SMA. The fetus of family 2 also harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, while the copy number of SMN2 gene was normal, suggesting that the fetus was a SMA patient too. The fetus of family 3 harbored heterozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus was a carrier.@*CONCLUSION@#DHPLC can effectively screen carriers of SMA mutations. Combined DHPLC and MLPA can provide accurate diagnosis for fetuses with a high risk for SMA.


Subject(s)
Child , Female , Humans , Pregnancy , Chromatography, High Pressure Liquid , Homozygote , Muscular Atrophy, Spinal , Diagnosis , Nucleic Acid Amplification Techniques , Prenatal Diagnosis , Sequence Deletion , Survival of Motor Neuron 1 Protein , Genetics , Survival of Motor Neuron 2 Protein , Genetics
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