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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 explore the etiology, clinical diagnosis and treatment strategy of Lesch Nyhan syndrome.Methods:We retrospectively analyzed 2 patients with severe dyskinesia, mental retardation and complicated renal calculi who were admitted to the first people's Hospital of Zhengzhou in August 2019. Case 1, male, 9 years old, had multiple urinary calculi for 1 year. The patient came to the local hospital because double multiple kidney stones and bladder stonesa year ago. The patient had been treated with transurethral holmium laser lithotripsy for bladder stones. The results of infrared spectrum showed that the bladder stone was anhydrous uric acid stone. A week ago, color Doppler ultrasound showed multiple kidney stones and bladder stones. The patient was underdeveloped, mentally retarded and had a full-term cesarean section. There was no history of hypoxia, asphyxia and rescue of the patient. He had the following clinical manifestations: In the waking state, he was no language response to any stimulation. The nasolabial fold on the right was shallow and the corner of the mouth was oblique to the left. He lost the large movements such as lifting head, sitting alone, standing. The trunk showed torsion spasticity, limb muscle strength 2-3, limbs showing spastic hypertonia, limb joints stiff, hands showing fist-like, no involuntary movement and muscle fasciculation. The biceps reflex and knee tendon reflex were not elicited, and the pathological reflex was positive. Serum uric acid was 517 μmol/L. The Case 2 came from the same family, male, 6 years old, had the similar symptoms to his elder brother case 1. The family members complained on behalf of the child about intermittent fever for more than 2 years. The imaging examination of case 2 revealed kidney stones. Serum uric acid was 373 μmol/L. Whole Exome Sequencing and Sanger Sequencing were used to find the genetic causes of the two siblings. The NCBI-Homologene database was used to find the homologous sequence of the human HPRT1 gene, and the human HPRT1 gene sequence was compared with other species to analyze the protein conservation. The online website PredictProtein (http: //www.predactprotein) was used to predict the two-dimensional structure of the HPRT1 gene. The reported cases were summarized and same with the treatment plan.Results:A De novo mutation [c.571T>G(p.Tyr191Asp)] was found in the HPRT1 gene of the child, which was inherited from the mother. Lesch Nyhan syndrome can be diagnosed by the results of gene examination combined with clinical manifestations. The amino acid Tyr at the 191 position and the amino acids before and after it were highly conserved. Amino acid 191 was involved in the β-strand of the protein. We treated the patients with the lowest dose of allopurinol and children's conventional dose of potassium sodium bicitrate granules, and low purine diet. After 3 months of treatment, the serum uric acid was decreased, and the urinary calculi did not increase significantly.Conclusions:Combining with the clinical manifestations of children, HPRT1 gene might be the cause of pediatric disease and the two siblings could be diagnosed as Lesch-Nyhan syndrome. For such patients, the lowest dose of allopurinol and children's conventional dose of potassium sodium hydrogen citrate granule combined with diet could be more effective.
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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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Objective@#To explore the genetic basis of a pedigree affected with hereditary spherocytosis.@*Methods@#Peripheral blood samples were collected from 17 members of the pedigree. Genomic DNA of the proband was subjected to next generation sequencing. Candidate variant was validated by co-segregation analysis. pCAS2c.5798+ 1G and pCAS2c.5798+ 1A plasmids were constructed by homologous recombination and transfected into 293T cells. Reverse transcription PCR, TA cloning and Sanger sequencing were used to analyze the effect of candidate variant on splicing. Meanwhile, peripheral blood RNAs were extracted to analyze the effect of candidate variant on splicing in vivo.@*Results@#The proband was found to carry a c. 5798+ 1G>A variant of the SPTB gene. The variant has co-segregated with the phenotype in the pedigree. In vitro and in vivo splicing experiments confirmed that the mutation has significantly affected the splicing, resulting in shift of reading frame and produced a premature termination codon.@*Conclusion@#The novel c. 5798+ 1G>A variant of the SPTB gene probably underlies the pathogenesis of hereditary spherocytosis in this pedigree.
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OBJECTIVE@#To explore the genetic basis of a pedigree affected with hereditary spherocytosis.@*METHODS@#Peripheral blood samples were collected from 17 members of the pedigree. Genomic DNA of the proband was subjected to next generation sequencing. Candidate variant was validated by co-segregation analysis. pCAS2(c.5798+1G) and pCAS2(c.5798+1A) plasmids were constructed by homologous recombination and transfected into 293T cells. Reverse transcription PCR, TA cloning and Sanger sequencing were used to analyze the effect of candidate variant on splicing. Meanwhile, peripheral blood RNAs were extracted to analyze the effect of candidate variant on splicing in vivo.@*RESULTS@#The proband was found to carry a c.5798+1G>A variant of the SPTB gene. The variant has co-segregated with the phenotype in the pedigree. In vitro and in vivo splicing experiments confirmed that the mutation has significantly affected the splicing, resulting in shift of reading frame and produced a premature termination codon.@*CONCLUSION@#The novel c.5798+1G>A variant of the SPTB gene probably underlies the pathogenesis of hereditary spherocytosis in this pedigree.
Subject(s)
Humans , Codon, Nonsense , Genetics , Genetic Variation , HEK293 Cells , Mutation , Genetics , Pedigree , Plasmids , RNA Splicing , Spectrin , Genetics , Spherocytosis, Hereditary , Genetics , TransfectionABSTRACT
Objective@#To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF).@*Methods@#Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing.@*Results@#The fetus was found to carry compound heterozygous variants c. 1440+ 1G>A and c. 925G>T of the NPHS1 gene, which were respectively inherited from its mother and father.@*Conclusion@#Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.
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OBJECTIVE@#To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF).@*METHODS@#Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing.@*RESULTS@#The fetus was found to carry compound heterozygous variants c.1440+1G>A and c.925G>T of the NPHS1 gene, which were respectively inherited from its mother and father.@*CONCLUSION@#Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.
Subject(s)
Female , Humans , Pregnancy , Fetus , Finland , Heterozygote , Membrane Proteins , Genetics , Nephrotic Syndrome , Diagnosis , Prenatal DiagnosisABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical manifestations and mutation of MYH9 gene in a large Chinese family affected with MYH9-related thrombocytopenia.</p><p><b>METHODS</b>After informed consent was obtained; clinical examination and history investigation was performed on 29 members of the family. DNA was extracted using a standard method, then exons 1 to 40 and their corresponding exon-intron junctions of the MYH9 gene were amplified with PCR and subjected to Sanger sequencing. The results were compared to reference sequence from the University of California, Santa Cruz (UCSC) to screen the mutation. PCR and Sanger sequencing was performed on genome DNA of all family members to confirm the identified mutation.</p><p><b>RESULTS</b>The clinical manifestations of family members were prominently heterogeneous. Four affected members showed hearing loss or deafness, two affected members showed nephritis or kidney failure, and other affected members was only characterized by mild bleeding or with no obvious symptoms. A heterozygous missense mutation c.4270G>A (p.Aspl841Asn) in exon 30 of the MYH9 gene was identified in all affected members from this family, which also co-segregated with the phenotype.</p><p><b>CONCLUSION</b>A missense mutation c.4270G>A (p.Aspl841Asn) within the exon 30 of the MYH9 gene was identified to be associated with MYH9-related thrombocytopenia in a Chinese family.</p>
Subject(s)
Female , Humans , Male , Amino Acid Sequence , Asian People , Genetics , China , DNA Mutational Analysis , Exons , Genetics , Family Health , Genetic Predisposition to Disease , Ethnology , Genetics , Heterozygote , Molecular Motor Proteins , Genetics , Mutation, Missense , Myosin Heavy Chains , Genetics , Pedigree , Sequence Homology, Amino Acid , Thrombocytopenia , Ethnology , GeneticsABSTRACT
Objective To analyse the effect of progesterone on peripheral blood corticotropin releasing hormone ( CRH ) and delivery time in women with premature rupture of membranes ( PROM ) .Methods 80 patients who were diagnosed with PROM in Department of Obstetrics and Gynecology, China Medical University were collected.Randomly divided into dexamethasone (DEX) group, dexamethasone plus progesterone (DEX+P) group, progesterone ( P) group and control group, three groups were detected on admission, admission 24 h, 48 h on peripheral white blood cell count, C-reaction protein, CRH level and time of delivery, neonatal weight, and analysis of CRH the level of the correlation and delivery time.Results Compared with the other three groups, the level of CRH in peripheral blood of DEX group were higher (P<0.05);CRH (P<0.05) increased faster;shorter delivery time (P<0.05); the level of CRH was negatively correlated with delivery time (r=-0.832, P<0.05).The results were statistically significant.Conclusion Dexamethasone treatment can make the premature rupture of fetal membranes of peripheral blood CRH levels rise, shorten the delivery time, progesterone can inhibit this process.
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<p><b>OBJECTIVE</b>To explore the possible roles of polymorphisms of SPO11 and glutathionine S-transferase (GST) genes in idiopathic male infertility in a ethnic Han Chinese population from Henan.</p><p><b>METHODS</b>Multiplex PCR and DNA sequencing were performed to determine the SPO11 c.517C>T(rs28368082) and GST genes (GSTM1, GSTT1, GSTP1) polymorphisms in 216 idiopathic male infertility cases and 198 normal samples.</p><p><b>RESULTS</b>The frequencies of the SPO11 CC and CT genotypes were 87.5% (189/216) and 12.5% (27/216) in the patients, and 97.5% (193/198) and 2.5% (5/198) in the controls, respectively. The frequencies of SPO11 CC and CT genotypes, the A>G transition at nucleotide 313 in the exon 5 of the GSTP1 gene, and the frequencies of combined genotypes GSTM1 (-/-), GSTT1 (+/+), GSTP1 (AA) and SPO11 (CT) were significantly different between the two groups (P<0.05).</p><p><b>CONCLUSION</b>The rs28368082 polymorphism of the SPO11 gene, the A>G transition at nucleotide 313 in the exon 5 of the GSTP1 gene, and the combined genotypes of GSTM1 (-/-), GSTT1 (+/+), GSTP1 (AA) and SPO11 (CT) may be associated with idiopathic male infertility in ethnic Han Chinese.</p>