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Objective:To analyze clinical characteristics of and causative genes in two families with dystrophic epidermolysis bullosa, and to reveal the pathogenesis of the disease and mechanisms underlying phenotypic differences between patients.Methods:DNA was extracted from peripheral blood samples of members from two families with dystrophic epidermolysis bullosa, and subjected to high-throughput sequencing and Sanger sequencing.Results:The clinical manifestations of the 2 probands in the 2 families were consistent with the diagnosis of dystrophic epidermolysis bullosa, and the symptoms of the proband in family 1 were more serious than those of other patients in the family. Genetic testing showed that all patients in family 1 carried a mutation c.6082G>C (p.G2028R) in the COL7A1 gene, and the proband and her phenotypically normal mother and uncle also carried a splice-site mutation c.7068+2 (IVS91) T>G in the COL7A1 gene, both of which were first reported. The proband in family 2 carried the mutations c.6081_6082 ins C (p.G2028Rfs*71) and c.1892G>A (p.W631X, first reported) in the COL7A1 gene, which were inherited from her father and mother, respectively.Conclusion:The two pathogenic mutations may be the molecular mechanism underlying the severe clinical phenotype in the proband in family 1; the first reported mutations enriched the mutation spectrum of the COL7A1 gene.
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Dystrophinopathies, including Duchenne muscular dystrophy, Becker muscular dystrophy and dilated cardiomyopathy, are X-linked recessive genetic disorders due to variants of the dystrophin gene, which can seriously affect quality of life and health. Genetic diagnosis plays a crucial role in their diagnosis, treatment, and prevention. How to rationally select and standardize the use of various genetic techniques is a skill that clinicians must acquire. By compiling expertise of experts from the relevant areas and guidelines published home and abroad, this consensus has provided a guidance from the perspective of genetic diagnosis for the selection of genetic techniques, testing strategies, and detection process for dystrophinopathies.
Subject(s)
Humans , Quality of Life , Consensus , Dystrophin/genetics , Muscular Dystrophy, Duchenne/therapy , Cardiomyopathy, Dilated/genetics , ElectrocardiographyABSTRACT
OBJECTIVE@#To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome.@*METHODS@#Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2.@*RESULTS@#The proband of pedigree 1 was a fetus at 23+5 weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up.@*CONCLUSION@#The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.
Subject(s)
Female , Humans , Pregnancy , Pedigree , Cerebellum/abnormalities , Abnormalities, Multiple/diagnosis , Eye Abnormalities/diagnosis , Kidney Diseases, Cystic/diagnosis , Phosphoric Monoester Hydrolases/genetics , Retina/abnormalities , East Asian People , MutationABSTRACT
OBJECTIVE@#To explore the genetic characteristics of a fetus with a high risk by maternal serum screening during the second trimester.@*METHODS@#Genetic counseling was provided to the pregnant woman on March 22, 2020 at Henan Provincial People's Hospital. G-banded chromosomal karyotyping and array comparative genomic hybridization (aCGH) were carried out on the amniotic fluid sample and peripheral blood samples from the couple.@*RESULTS@#The fetus and the pregnant woman were respectively found to have a 46,XX,der(6)t(6;14)(q27;q31.2) and 46,XX,t(6;14)(q27;q31.2) karyotype, whilst the husband was found to have a normal karyotype. aCGH analysis has identified a 6.64 Mb deletion at 6q26q27 and a 19.98 Mb duplication at 14q31.3q32.33 in the fetus, both of which were predicted to be pathogenic copy number variations. No copy number variation was found in the couple.@*CONCLUSION@#The unbalanced chromosome abnormalities in the fetus have probably derived from the balanced translocation carried by the pregnant woman. aCGH can help to determine the types of fetal chromosome abnormalities and site of chromosomal breakage, which may facilitate the prediction of fetal outcome and choice for subsequent pregnancies.
Subject(s)
Pregnancy , Female , Humans , Comparative Genomic Hybridization , DNA Copy Number Variations , Translocation, Genetic , Chromosome Aberrations , Fetus , Prenatal DiagnosisABSTRACT
OBJECTIVE@#To explore the clinical features and genetic etiology of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH).@*METHODS@#Two children with MICPCH who were presented at the Henan Provincial People's Hospital between April 2019 and December 2021 were selected as the study subjects. Clinical data of the two children were collected, along with peripheral venous blood samples of them and their parents, and amniotic fluid sample of the mother of child 1. Whole exome sequencing (WES), array-comparative genomic hybridization (aCGH) and real-time quantitative PCR (qPCR) were carried out for the children, their parents and the fetus. The pathogenicity of candidate variants were evaluated.@*RESULTS@#Child 1 was a 6-year-old girl featuring motor and language delay, whilst child 2 was a 4.5-year-old girl mainly featuring microcephaly and mental retardation. WES revealed that child 2 has harbored a 158.7 kb duplication in Xp11.4 (chrX: 41446160_41604854), which has encompassed exons 4~14 of the CASK gene. The same duplication was not found in either of her parents. aCGH revealed that child 1 has harbored a 29 kb deletion at Xp11.4 (chrX: 41637892_41666665), which encompassed exon 3 of the CASK gene. The same deletion was not found in either of her parents and the fetus. The above results were confirmed by qPCR assay. Above deletion and duplication were not found in the ExAC, 1000 Genomes and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PS2+PM2_Supporting).@*CONCLUSION@#The deletion of exon 3 and duplication of exons 4~14 of the CASK gene probably underlay the pathogenesis of MICPCH in these two children, respectively.
Subject(s)
Humans , Child , Female , Child, Preschool , Microcephaly/genetics , Developmental Disabilities/genetics , Intellectual Disability/complications , Comparative Genomic Hybridization , MutationABSTRACT
OBJECTIVE@#To explore the genetic basis for fetus with bilateral lateral ventriculomegaly.@*METHODS@#Fetus umbilical cord blood and peripheral blood samples of its parents were collected. The fetus was subjected to chromosomal karyotyping, whilst the fetus and its parents were subjected to array comparative genomic hybridization (aCGH). The candidate copy number variation (CNV) were verified by qPCR, Application goldeneye DNA identification system was used to confirm the parental relationship.@*RESULTS@#The fetus was found to have a normal karyotype. aCGH analysis indicated that it has carried a 1.16 Mb deletion at 17p13.3, which partially overlapped with the critical region of Miller-Dieker syndrome (MDS), in addition with a 1.33 Mb deletion at 17p12 region, which is associated with hereditary stress-susceptible peripheral neuropathy (HNPP). Its mother was also found to harbor the 1.33 Mb deletion at 17p12. qPCR analysis confirmed that the expression levels of genes from the 17p13.3 and 17p12 regions were about the half of that in the normal control, as well as the maternal peripheral blood sample. Parental relationship was confirmed between the fetus and its parents. Following genetic counseling, the parents has chosen to continue with the pregnancy.@*CONCLUSION@#The fetus was diagnosed with Miller-Dieker syndrome due to the de novo deletion at 17p13.3. Ventriculomegaly may be an important indicator for prenatal ultrasonography in fetuses with MDS.
Subject(s)
Pregnancy , Female , Humans , Classical Lissencephalies and Subcortical Band Heterotopias , Comparative Genomic Hybridization , DNA Copy Number Variations , Fetus , Hydrocephalus , Prenatal Diagnosis , Chromosome DeletionABSTRACT
OBJECTIVE@#To explore the genetic etiology of two patients with developmental delay and intellectual disability.@*METHODS@#Two children who were respectively admitted to Henan Provincial People's Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions.@*RESULTS@#Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents.@*CONCLUSION@#The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.
Subject(s)
Humans , Child , Female , Child, Preschool , Intellectual Disability/genetics , Comparative Genomic Hybridization , Chromosome Disorders/genetics , Chromosome Deletion , Magnetic Resonance Imaging , Chromosomes, Human, Pair 22 , Developmental Disabilities/genetics , Carrier Proteins/genetics , Nerve Tissue Proteins/geneticsABSTRACT
Objective:To provide experimental evidence for genetic counseling and prenatal diagnosis by analyzing the clinical characteristics, screening and identification of the function of suspicious variants in a X-1inked spondyloepiphyseal dysplasia tarda (SEDT) family.Methods:The family members' medical history, general physical examination, femur, spine X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA was extracted from these samples. Sequencing clinical whole exons of proband DNA by targeted gene high-throughput sequencing method, then analysis sequencing data. The suspicious mutation was confirmed in pedigree members by PCR and Sanger sequencing. Reverse transcription polymerase chain reaction (RT-PCR) experiments of total RNA from blood lymphocytes were performed. The amplification of exons 3 and 4 of the pathogenic gene were amplified and identified by agarose gel. The expression of the pathogenic gene was also detected.Results:Three affected males of the family were diagnosed with SEDT according to their clinical and radiological features. A nonsense mutation in the transport protein particle complex subunit 2 ( TRAPPC2) gene NM_001011658: c.91A>T (p.K31*) was found in the proband using whole exome sequencing. This variation was also detected in his cousin, but not in non-phenotypic members of the family. The RT-PCR result for amplification of exon 3 and 4 of peripheral blood lymphocytes was the same as those of normal controls, indicating that the mutation did not affect the splicing of transcripts. qPCR results showed that the transcriptional expression of TRAPPC2 in patients was significantly lower than that in family normal controls and normal people controls. Conclusion:Identification of the novel nonsense mutation (c.91A>T) in the SEDT family enables early patients screening, carrier detection, genetic counseling, prenatal diagnosis, and clinical prevention and treatment. The detailed genotype/phenotype descriptions contribute to the SEDT mutation spectrum. The study of the function of TRAPPC2 mutation will help to further elucidate the role of sedlin in cartilage.
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Objective:To explore the genetic etiology of fetuses with high suspicion of congenital skeletal malformation detected by prenatal ultrasound.Methods:This retrospective study collected 21 pregnant women with highly suspected fetal skeletal malformation indicated by ultrasound (the couples had no skeletal malformation) at Institute of Medical Genetics, Henan Provincial People's Hospital from January 2019 to August 2020. Amniotic fluid/umbilical cord blood of the fetus and peripheral blood of the couples were obtained for karyotype analysis, chromosomal microarray analysis, and whole-exome sequencing. Sanger sequencing was performed for the "pathogenic" "suspected pathogenic" "variants of uncertain significance" variants detected by whole exome sequencing. Genetic etiology of the 21 fetuses was described.Results:A total of five chromosomal abnormalities were detected, including four cases of trisomy 21 and one trisomy 18. Chromosome microarray analysis detected one case of abnormal copy number variation, 16 p11.2 microdeletion syndrome. Ten cases of monogenic diseases were found by whole exome sequencing and eight genes were involved ( SGMS2, FGFR3, DYNC2H1, WDR35, TBX5, COL2A1, FGFR2, and ALPL). Totally, 14 variations were detected, among which seven were novel variations (c.8129T>A, c.7126G>A, c.10307_10320del, and c.2641G>T in DYNC2H1 gene; c.3085G>A and c.491G>A in WDR35 gene; c.1070G>T in COL2A1 gene). Conclusions:For fetus, whose parents have no skeletal malformation, highly suspected of congenital malformation of skeletal system by prenatal ultrasound, genetic factor is the primary reason, including chromosomal abnormalities, copy number variations, and monogenic mutations.
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Objective:To investigate the prenatal diagnosis and genetic analysis of 9p24 microdeletion in six fetuses.Methods:Genetic data of six pregnant women with positive results of serological Down's syndrome screening at Henan Provincial People's Hospital from January 2018 to January 2020 were retrospectively collected and analyzed. Amniotic fluid and the parents' peripheral blood samples were subjected to G banding and array comparative genomic hybridization (aCGH) analysis. Detected copy number variation (CNV) were classified based on the American College of Medical Genetics and Genomics (ACMG) scoring standard.Results:Six fetuses showed no abnormalities in ultrasound during the second trimester as well as in karyotyping. A chromosome deletion of 1 019~6 001 kb at 9p24 was found in all six fetuses by aCGH, referring to disease-related genes DMRT1, SMARCA2, DOCK8, etc. The deletion of case 3 was inherited from the asymptomatic father, and the other fetal five were all de novo mutations. Cases 1, 2, 5, and 6 were pathogenic/likely pathogenic CNV carriers and cases 3 and 4 were CNV of unknown clinical significance carriers. After genetic counseling, cases 1, 2, 5, and 6 chose to terminate the pregnancies; cases 3 and 4 continued and gave birth to normal offspring. Conclusions:Fetuses with 9p24 microdeletion lack specific phenotypes before born. DMRT1 and SMARCA2 may be the key genes in this region.
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Objective:To investigate the association between prenatal genotype and phenotype of 16p13.11 microdeletion syndrome, aiming to provide a reference for prenatal diagnosis and genetic counseling.Methods:This retrospective study analyzed the results of comparative genomic hybridization microarray and low-coverage whole genome sequencing performed on 4 230 pregnant women in the Henan Provincial People's Hospital from July 2018 to July 2021. Indications for prenatal diagnosis, pedigree information and pregnancy outcomes of 17 fetuses with 16p13.11 microdeletion were described.Results:Prenatal diagnostic indications in the 17 fetuses were ultrasound abnormalities in five cases (increased nuchal translucency in four and cerebral ventriculomegaly with 10.7 mm in one), inter-twin weight discordance over 20% in one case, high risk in five cases and marginal risk in one in trisomy-21 serum screening, advanced maternal age in three cases (one with echogenic intracardiac focus in the left ventricle and two with normal ultrasound images) and adverse pregnancy history in two cases with normal ultrasound images. Pedigree verification that performed on 12 cases revealed that five were caused by de novo mutations and seven were inherited from their parents. The follow-up results showed that five cases were terminated, two lost to follow-up and 10 born alive (inheritance patterns were de novo mutations in three cases, parental inheritance in six and unknown pattern in one). These 10 infants were followed up from age 7 months to 3 years and 2 months and the results showed that one case was born with choroid plexus cyst of the left ventricle and presented instability of gait at 1 year and 3 months; one was a premature infant with 33 gestational weeks whose parents reported his language ability was not well at 2 years and 1 month old but without other abnormalities; one case had low muscle tone and was unable to keep head upright at 3 months who recovered at 5 months old after rehabilitation treatment according to the parents' report; all seven parents in the remaining seven cases reported no abnormalities. Conclusions:There was no specific prenatal diagnostic indication for 16p13.11 microdeletion syndrome. Genetic tracing, pregnancy outcome analysis and follow-up surveillance would provide reference for genetic counseling of 16p13.11 microdeletion syndrome.
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Objective:To analyze the clinical and genetic characteristics of a 27-year-old male patient with intellectual disability and his pedigree to provide a reference for genetic counseling and prenatal diagnosis.Methods:G-banding and array comparative genomic hybridization (aCGH) were performed to analyze the karyotypes and genomic copy number variations of the proband (Ⅲ-1) and his family members. Based on the results, prenatal diagnosis was performed for one pregnant woman (Ⅲ-2) in the pedigree who is the sister of the proband.Results:All karyotyping were normal in the family members, while aCGH results showed a 1 533 kb microduplication in the Xq25 region of the proband, his mother (Ⅱ-3), his uncle (Ⅱ-2), and his sister (Ⅲ-2), which was confirmed to be pathogenic. The proband and his uncle presented with intellectual disability, bradylalia, and facial dysmorphism. In contrast, his mother and sister showed normal phenotypes. His sister's fetal karyotype and aCGH results were normal, and the pregnancy continued. A male baby (Ⅳ-1) was delivered vaginally at term and showed no physical or intellectual abnormalities during a 46-month follow-up.Conclusions:Xq25 microduplication might be the cause of intellectual disability in the proband. STAG2 is probably the essential gene in Xq25 region.
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OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH).@*METHODS@#PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree.@*RESULTS@#The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual.@*CONCLUSION@#The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Subject(s)
Female , Humans , Adenosine Deaminase/genetics , China , Mutation , Pedigree , Pigmentation Disorders/congenital , RNA-Binding Proteins/geneticsABSTRACT
OBJECTIVE@#To explore the genetic basis for a couple who had developed polyhydramnios during three pregnancies and given birth to two liveborns featuring limb contracture, dyspnea and neonatal death.@*METHODS@#Whole-exome sequencing (WES) was carried out on fetal tissue and peripheral blood samples from the couple. Suspected variants were verified by Sanger sequencing.@*RESULTS@#The fetus was found to harbor homozygous nonsense c.3718C>T (p.Arg1240Ter) variants of the CNTNAP1 gene, which were respectively inherited from its mother and father. The variant was unreported previously. According to the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP4).@*CONCLUSION@#The novel homozygous nonsense variants of the CNTNAP1 gene probably underlay the lethal congenital contracture syndrome type 7 (LCCS7) in this pedigree. Above finding has enabled genetic counseling and prenatal diagnosis for the family.
Subject(s)
Female , Humans , Infant, Newborn , Pregnancy , Cell Adhesion Molecules, Neuronal , China , Contracture/genetics , Mutation , Pedigree , Exome SequencingABSTRACT
OBJECTIVE@#To analyze the clinical features and genetic variant in a patient with Usher syndrome.@*METHODS@#Whole exome sequencing was carried out for the patient. Suspected variants were validated by Sanger sequencing of her parents and fetus.@*RESULTS@#The proband was found to harbor compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene (NM_033056), which were respectively inherited from her father and mother. The same variants were not detected in 100 healthy controls. Based on the guidelines of the American Society of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PP4). By prenatal diagnosis, her fetus was found to carry the c.4095_4096insA variant. After birth, the child has passed neonatal hearing screening test, and no abnormal auditory and visual function was found after the first year.@*CONCLUSION@#The compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene probably underlay the Usher syndrome is this proband.
Subject(s)
Child , Female , Humans , Infant, Newborn , Pregnancy , Cadherin Related Proteins , Cadherins/genetics , China , Genetic Testing , Pedigree , Prenatal Diagnosis , Usher Syndromes/geneticsABSTRACT
Objective:To explore the accuracy of array comparative genomic hybridization(aCGH) in the unexpected detection of Duchenne muscular dystrophy ( DMD) gene duplication/deletion in prenatal diagnosis. Methods:A retrospective analysis was performed on 31 cases with DMD gene duplication/deletion detected by aCGH among 5 025 prenatal diagnosis samples without family history of DMD in Henan Provincial People's Hospital from July 2018 to December 2019. The multiplex ligation-dependent probe amplification (MLPA) method was used to verify the above results. The American College of Medical Genetics and Genomics (ACMG) guideline was referred for pathogenicity analysis of the detected duplicates/deletions. Descriptive analysis was adopted in analysis. Results:The total unexpected DMD gene duplication/deletion rate was 0.62% (31/5 025), among which 25 cases were with microduplication/microdeletion ≤ 200 kb and six were >200 kb; there were 24 cases of deletion, seven cases of duplication; exon or intron duplication/deletion were accounted for 19 and 12 cases, respectively. According to the five classification standards of ACMG guideline, there were 17 cases with pathogenic variants and 14 cases with uncertain pathogenicity/likely benign variants. Of the 19 with exon mutations, 17 cases were DMD intragenic variants, and two cases involved variants in and outside DMD gene, which were verified by MLPA whose results were all positive. Conclusions:The duplication/deletion of exon region of DMD gene detected by aCGH technique is accurate and reliable, which plays an important role in the diagnosis of DMD. For these cases involved both internal and external regions of DMD gene, aCGH can identify the upstream and downstream breaking points of DMD gene, thus providing the basis for ACMG grading.
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Objective:To summarize the diagnosis features of the prenatal genetic diagnosis of fetal renal cystic disease and to explore the clinical feasibility and significance of prenatal genetic diagnosis of congenital cystic nephrosis.Methods:A total of 25 fetuses with congenital renal cystic disease were examined via invasive prenatal diagnosis in Henan Provincial People's Hospital from June 2017 to September 2019. Amniotic fluid samples were extracted by amniocentesis. Chromosomal microarray analysis (CMA) were performed in 17 cases. In addition to CMA, the other 8 cases were analyzed by G-band karyotype. Whole exome sequencing (WES) was performed in 6 cases which got normal results by CMA and karyotype, and highly suspected as hereditary disease.Results:Of the 25 fetuses assessed, 4 cases (16.0%) pathogenic copy number variation (pCNV) were found, including 2 cases of 17q12 deletion, 1 case of 10p15.1p14 deletion and 1 case of 4q21.28q22.1 deletion(including PKD2 gene). There were 8 cases without chromosome abnormality by karyotype analysis. Six clinical WES analysis found NPHS1 gene c.1440+1 G>A and c.925G > T mutations were related to Finnish type congenital nephrotic syndrome in 1 case, PKD1 gene c.6878C>T mutation was related to autosomal dominant polycystic kidney disease (ADPKD) in 1 case, and there was no definitive mutation in 4 cases. Conclusions:CMA and next generation sequencing are powerful tools for accurate diagnosis, treatment and genetic counseling of fetal congenital renal cystic diseases. For congenital cystic nephropathy, genetic detection is helpful to clarify the etiology, and provide more exactly informations for prognosis evaluation, treatment and family genetic counseling.
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OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with mental retardation.@*METHODS@#G-banded karyotyping analysis and single nucleotide polymorphism microarray (SNP array) were used to detect the genetic variants within the family, and the origin of the variants was analyzed using UPDtool Statistics software.@*RESULTS@#The patient, a 26-year-old female, was found to have a chromosomal karyotype of 46,XX,dup(4)(q28.2q31.3),and SNP array revealed a 25.71 Mb duplication at 4q28.2-q31.3. The duplication was inherited from her father, and her fetus was found to carry the same duplication.@*CONCLUSION@#The duplication of the patient probably underlay the mental retardation. The gender of the carrier and parental origin of the duplication might have led to the variation in their clinical phenotype.
Subject(s)
Adult , Female , Humans , Male , Chromosome Banding , Genetic Testing , Karyotyping , Pedigree , Trisomy/geneticsABSTRACT
Objective:To investigate the genetic etiology of a child with epilepsy accompanied by motor retardation.Methods:A patient with epilepsy and motor retardation in Henan Provincial People′s Hospital in January 2020 and his parents′ peripheral blood 2 mL were collected.G-banded karyotyping and array-based comparative genomic hybridization (aCGH) were used to analyze the duplication / deletion of chromosome segments in child and her pa-rents.Results:The karyotype of the patient revealed 46, XX, and add(19)(p13.3→qter), whereas aCGH detected a 9.50 Mb duplication at 19q13.33q13.43[arr(hg19)(49593920_59092570)×3]. This region contains 471 genes.No abnormality was discovered in the karyotyping and aCGH analysis of the patient′s parents.The phenotypes of the patient conformed to the previously reported clinical characteristics of 19q13.3 duplication.Conclusions:The de novo 19q13.3 duplication is the cause of epilepsy and motor development retardation for the patient.Combined with aCGH, the traditional G banding is valuable to diagnose the patient with developmental delay.
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In 2014, the training of clinical medical genetics was included in the training sequence of resident standardized training in China. The standardized training of clinical geneticist in China started relatively late. As a whole, the training and qualification system of clinical hereditary physicians are still in the process of development and perfection. Based on "Rules for the training of department of medical genetics", basic medical genetics resident training system was established in Henan Provincial People's Hospital. Additionally, we took advantage of interactive online education platform, multiple disciplinary team, the analysis of positive case report, literature report and other teaching practices combined with the tutor system. After 4 years of exploration and practice, the program can quickly improve the residents' comprehensive ability, such as theoretical knowledge, professional literacy, clinical practice skills, and scientific research ability.