ABSTRACT
OBJECTIVE@#To explore the clinical and genetic characteristics of two children with developmental delay.@*METHODS@#Two children who had presented at the Children's Hospital Affiliated to Shandong University on August 18, 2021 were enrolled as the study subjects. Clinical and laboratory examination, chromosomal karyotyping and high-throughput sequencing were carried out for both children.@*RESULTS@#Both children had a 46,XX karyotype. High-throughput sequencing showed that they have respectively carried a c.489delG (p.Q165Rfs*14) and a c.1157_1158delAT (p.Y386Cfs*22) frameshifting variant of the CTCF gene, both had a de novo origin and were unreported previously.@*CONCLUSION@#The CTCF gene variants probably underlay the development delay in the two children. Above discovery has enriched the mutational spectrum of the CTCF gene and has important implications for revealing the genotype-phenotype correlation for similar patients.
Subject(s)
Child , Humans , Developmental Disabilities/genetics , High-Throughput Nucleotide Sequencing , Intellectual Disability/genetics , Karyotyping , MutationABSTRACT
Objective:To investigate the effect of unilateral biportal endoscopy (UBE) through extraforaminal approach in the treatment of extra canal lumbosacral nerve entrapment.Methods:Seventeen patients with extra canal lumbosacral nerve root entrapment were treated by UBE through extraforaminal approach in Tianjin Hospital from January 2020 to March 2022, including 9 males and 8 females with an average age of 59.2 years (range 45-71 years). All 17 patients had lower limb radiation pain, numbness, and weakness with or without intermittent claudication. MRI imaging examination showed L 4, 5 foramen stenosis with far lateral disc herniation in 2 case, and L 5S 1 foramen stenosis with far lateral disc herniation in 15 cases, and the height of intervertebral space decreased, resulting in the compression of exiting nerve root and ganglion. Among them, far-out syndrome was diagnosed in 7 cases and transitional lumbarsacral vertebrae was found in 12 cases. The incisions were designed 2 cm away form the projection of adjacent pedicles, while incision at S 1 was designed at the inner edge of the iliac bone due to the shielding of the ilium, taking the outer edge of the isthmus at the outer opening of the intervertebral foramen as the target of channels. The ventral and apical part of superior articular process (SAP) was gradually removed with high-speed burr from its outer edge and isthmus, and the occluded sacral ala and the lower edge of transverse process were removed when necessary. The hyperplastic ligament was removed to expose the exiting nerve root. The protruding intervertebral disc was removed at the ventral side of the nerve root. The far-out syndrome was decompressed laterally along the exiting nerve root until it is completely released. The results and stability were evaluated with visual analogue scale (VAS), Oswestry disability index (ODI), Macnab scores and dynamic X-ray film during follow-up. Results:The operation time was 45-85 min, with an average of 60 min. After remove of the SAP tip and enlarge of the intervertebral foramen, the exiting nerve root and disc protrusion were fully exposed, the exiting nerve root was exposed and released laterally until totally release without entrapment in far out syndrome, and the nerve could be decompressed completely. The symptoms were significantly relieved after operation, and imaging examination showed that facet joints were preserved. During follow-up, the pain and function improved continuously. At final follow-up, the improve rate of VAS and ODI were 85.2% and 86.2%, respectively, and the results were excellent in 15 cases and good in 2 case according to Macnab score, and there was no lumbar instability on dynamic lumbar X-ray film.Conclusion:Extra canal lumbosacral nerve entrapment can be treated by UBE through extraforaminal approach, with sufficient exposure, complete decompression and better preservation of lumbar stability.
ABSTRACT
Objective:To evaluate the safety and validity of enriched autologous bone marrow mesenchymal stem cells (BMSCs) and annular suture for repairing defect after lumbar discectomy.Methods:Enrichment of autologous BMSCs: autologous bone marrow blood was collected from 5 patients undergoing lumbar surgery, and nucleated cells were enriched on gelatin sponge particles by selective cell retention technique. From October 2016 to March 2019, 109 patients with lumbar disc herniation underwent discectomy with mobile microendoscopic discectomy technique, including 61 males and 48 females, aged 24-59 years. Discectomy group: 26 cases received simple discectomy. Suture group: 39 cases received annular suture after discectomy. BMSCs+suture group: 44 cases received intradisc transplantation of gelatin sponge particles enriched with autologous BMSCs and annular suture after discectomy. The perioperative conditions were recorded, with visual analogue scale (VAS), Oswestry dysfunction index (ODI), Pfirrmann grade of disc degeneration, disc height and degree of herniationevaluated after operation.Results:In enrichment test with flow cytometry, the enrichment multiple of nucleated cells and target cells was 6.4±0.9 and 4.2±0.6 respectively, and BMSCs grew well in vitro. The operation time was 35-55 mins. 7 cases in the suture group were transferred to the discectomy group and 10 cases in the BMSCs+suture group were transferred to BMSCs group due to unsuccessful suture. There were no significant differences in VAS, ODI, Pfirrmann grade of disc degeneration, disc height and degree of herniation among the groups. There was no significant difference in intraoperative bleeding, postoperative drainage and length of hospital stay. The incision was healed without redness and swelling. 18 patients were followed up for 6 months, and 91 cases were followed up for 1-3 years (25.0±5.6 months). There was no interbody fusion, heterotopic ossification or infection during follow-up. VAS and ODI decreased significantly after operation in all patients. At final follow-up, the VAS improvement rate of BMSCs+suture group (81.7%±7.9%) was higher than discectomy group (73.0%±8.9%), suture group (74.0%±6.9%) and BMSCs group (75.3%±8.4%); the ODI improvement rate of BMSCs+suture group (91.9%±8.8%) was higher than discectomy group (86.2%±8.1%) and suture group (86.4%±5.5%). According to MRI, the Pfirrmann grade of disc increased 0.7 in discectomy group, 0.6 in suture group, while it did not increased significantly in BMSCs+suture group and BMSCs group, and the progress of Pfirrmann grade in BMSCs+suture group and BMSCs group were lighter than discectomy group and suture group.The disc height decreased in each group, the loss rate of disc height in BMSCs+suture group (17.2%±4.3%) was less than discectomy group (29.3%± 6.3%) and suture group (20.6%±5.7%); and suture group was less than discectomy group. The degree of herniation was reduced by more than 50% in all groups, while 1 case in discectomy group had herniation without clinical symptoms.Conclusion:Autologous BMSCs and annulus suture are safe and effective in repairing the defect after lumbar discectomy, which may help to slow down the degeneration of intervertebral disc.
ABSTRACT
Objective:To evaluate the value and efficacy of microscope-assisted minimally invasive anterior lumbar discectomy and zero-profile fusion (ALDF) for lumbar degenerative diseases.Methods:Anterior lumbar distractors were designed to maintain the distraction of intervertebral space and expose the posterior edge of the intervertebral space. From June 2018 to December 2020, 41 cases of lumbar degenerative diseases were treated with this operation, including 19 men and 22 women, aged 29-71 years old (average 42.1 years old). All patients had intractable low back pain. Imaging examination showed lumbar disc degeneration with narrow intervertebral space, including disc herniation with Modic changes in 7 cases, spinal stenosis with instability in 16 cases and spondylolisthesis in 18 cases. The involved levels included L 2,3 in 1 case, L 3,4 in 3 cases, L 2-L 4 in 1 case, L 4,5 in 17 cases and L 5S 1 in 19 cases. An incision was taken that was pararectus for L 2-L 4 and transverse for L 4-S 1, with the intervertebral disc exposed via extraperitoneal approach. The intervertebral space was released and distracted after discectomy in intervertebral space, and self-made distractors were used to maintain the space. Under microscope, the herniation, posterior annulus and osteophyte were removed for sufficient decompression, with a suitable self-anchoring cage implanted into the intervertebral space. The visual analogue score (VAS), Oswestry dysfunction index (ODI), intervertebral space height, lordosis angle and spondylolisthesis rate were evaluated. Results:Operations were performed successfully in all the patients. The operation time was 70-120 min with an average of 90 min, and the intraoperative blood loss was 15-70 ml with an average of 30 ml. No severe complication such as nerve or blood vessel injury occurred. The patients were followed up for 12 to 36 months, with an average of 18 months. At the last follow-up, VAS decreased from 6.4±2.3 to 1.1±0.9, and ODI decreased from 44.9%±16.9% to 5.8%±4.7%. Intervertebral space height recovered from 7.2±2.8 mm to 12.1±2.1 mm and lordosis angle recovered from 6.9°±4.8° to 10.1°±4.6°. X-ray showed significant recovery of intervertebral space height, lordosis angle and spondylolisthesis rate, with obvious interbody fusion and no displacement of cage. For 18 patients of spondylolisthesis, the slippage recovered from 16.6%±9.3% to 7.6%±5.3%, with an average improvement of 54.2%.Conclusion:Microscope-assisted minimally invasive ALDF can provide sufficient decompression and zero-profile fusion for lumbar degenerative diseases with satisfactory results during short-term follow-up.
ABSTRACT
OBJECTIVE@#To explore the genetic basis for a child manifesting with intellectual disability, language delay and autism spectrum disorder.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the child and his family members, and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and interpreted according to the guidelines of the American College of Medical Genetics and Genomics.@*RESULTS@#The child was found to harbor a heterozygous c.568C>T (p.Q190X) nonsense variant of the ADNP gene, which was not detected in either parent by Sanger sequencing.@*CONCLUSION@#The clinical and genetic testing both suggested that the child has Helsmoortel-van der Aa syndrome due to ADNP gene mutation, which is extremely rare in China.
Subject(s)
Child , Humans , Abnormalities, Multiple/genetics , Autism Spectrum Disorder/genetics , Autistic Disorder/genetics , Heterozygote , Homeodomain Proteins/genetics , Intellectual Disability/genetics , Mutation , Nerve Tissue Proteins/genetics , Rare DiseasesABSTRACT
OBJECTIVE@#To analyze the clinical and genetic characteristics of an infant girl featuring comprehensive developmental backwardness.@*METHODS@#The patient was subjected to clinical examination, gas chromatography mass spectrometry and next-generation sequencing (NGS).@*RESULTS@#The child was insensitive to sound, could not turn over, raise head, laugh or recognize his mother. Laboratory tests were all normal, but metabolic analysis suggested 3-methylglutaconic aciduria due to elevated 3-methylglutaconic acid and 3-methylglutaric acid. NGS has detected two compound heterozygous CLPB variants in the child, namely c.1085G>A and c.1700A>C, which were respectively inherited from her father and mother. Bioinformatic analysis predicted both variants to be pathogenic. The patient was diagnosed with 3-methylglutaconic aciduria type VII (MGCA7).@*CONCLUSION@#The MGCA7 in the child was probably caused by CLPB gene variants. NGS has provided a powerful diagnostic tool for this rare disorder.
Subject(s)
Female , Humans , Infant , Endopeptidase Clp , Genetics , Genetic Testing , High-Throughput Nucleotide Sequencing , Metabolism, Inborn Errors , GeneticsABSTRACT
OBJECTIVE@#To explore the clinical features and molecular basis of a Chinese pedigree with two siblings affected by cytochrome P450 oxidoreductase deficiency (PORD).@*METHODS@#Clinical features of the patients were reviewed, and their genomic DNA was subjected to next generation sequencing (NGS).@*RESULTS@#The two siblings presented peculiar facies, genital hypoplasia and skeletal deformity. NGS revealed that both have carried compound heterozygous variants of the POR gene, namely c.1370G>A and c.517-19_517-10delGGCCCCTGTGinsC, which were respectively inherited from their parents.@*CONCLUSION@#Both siblings were diagnosed with PORD based on sequencing of the POR gene. The newly discovered POR c.517-19_517-10delGGCCCCTGTGinsC has enriched the spectrum of PORD-related genetic variants.
ABSTRACT
OBJECTIVE@#To validate the diagnosis of an infant with elevated urine 3-methylglutaconic acid (3-MGA) through sequencing of the CLPB gene.@*METHODS@#Genomic DNA of the infant was sequenced by next generation sequencing (NGS), and candidate pathogenic variants were verified by Sanger sequencing and bioinformatics analysis.@*RESULTS@#NGS has revealed that the infant has carried a c.1085G>A (p.Arg362Gln) and a c.1700A>C (p.Tyr567Ser) of the CLPB gene, which were respectively inherited from her parents. Among these, c.1085G>A (p.Arg362Gln) is a novel variant which was unreported previously, and based on the ACMG guidelines, it was predicted to be a possible pathogenic variant.@*CONCLUSION@#Compound heterozygous variants c.1085G>A (p.Arg362Gln) and c.1700A>C (p.Tyr567Ser) of the CLPB gene probably underlay the disease in this infant. Genetic testing has confirmed the diagnosis.
ABSTRACT
OBJECTIVE@#To explore the genetic basis for a Chinese boy featuring developmental delay and epilepsy.@*METHODS@#Clinical data of the patient was collected. Genomic DNA of the patient and his parents was extracted and subjected to high-throughput sequencing. Pathogenicity of the variant was predicted and validated.@*RESULTS@#Sequencing results showed that the patient has carried a de novo c.1470delA (p.V491Ffs*6) variant of the UBE3A gene, which was predicted to be pathogenic.@*CONCLUSION@#The frameshift variant c.1470delA (p.V491Ffs*6) probably underlay the disorders in this child.
ABSTRACT
OBJECTIVE@#To explore the clinical and genetic features of a patient with mental retardation.@*METHODS@#G-Banding chromosomal karyotyping and high-throughput sequencing was carried out for the child. Suspected variant was validated in his family by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient was found to carry a de novo heterozygous c.4090G>T (p.Gly1364X) variant of the ASXL3 gene, which was known to predispose to Bainbridge-Ropers syndrome.@*CONCLUSION@#The nonsense c.4090G>T (p.Gly1364X) variant probably accounts for the disease in this patient.
Subject(s)
Child , Humans , Codon, Nonsense , Developmental Disabilities , Genetics , High-Throughput Nucleotide Sequencing , Intellectual Disability , Genetics , Phenotype , Syndrome , Transcription Factors , GeneticsABSTRACT
OBJECTIVE@#To explore the genetic basis of a proband with distinctive facial features, global developmental delay, seizures and hypoplasia of corpus callosum through next generation sequencing (NGS).@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Whole exome and flanking sequences were screened by NGS. Suspected variants were verified by Sanger sequencing.@*RESULTS@#The proband was found to carry a heterozygous c.2824G>T (p.G942X) variant of the ZEB2 gene, which was verified by Sanger sequencing to be a de novo variant.@*CONCLUSION@#The heterozygous c.2824G>T (p.G942X) variant of the ZEB2 gene probably underlies the Mowat-Wilson syndrome in the proband.
Subject(s)
Humans , Facies , Genetic Variation , Heterozygote , Hirschsprung Disease , Genetics , Intellectual Disability , Genetics , Microcephaly , Genetics , Exome Sequencing , Zinc Finger E-box Binding Homeobox 2 , GeneticsABSTRACT
OBJECTIVE@#To explore the genetic basis for a female patient featuring unstable head upright and hypotonia of limbs.@*METHODS@#The child was examined clinically. Peripheral blood samples of the child, her parents and siblings were collected. Genomic DNA was extracted and subjected to next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#DNA sequencing found that the patient has carried a de novo heterozygous c.354C>A (p.N118K) variant of the CHRND gene, which was not found in her parents and sibling. Bioinformatics analysis predicted that the variant was likely to be pathogenic. Literature review suggested that the phenotype of the patient was very similar to previously reported ones.@*CONCLUSION@#The child was diagnosed with slow-channel congenital myasthenic syndrome (SCCMS) type 3A caused by heterozygous variant of the CHRND gene. NGS has provided a powerful tool for the diagnosis of such disorders.
Subject(s)
Child , Female , Humans , Genetic Testing , Heterozygote , High-Throughput Nucleotide Sequencing , Mutation , Myasthenic Syndromes, Congenital , Genetics , Pathology , Receptors, Cholinergic , GeneticsABSTRACT
OBJECTIVE@#To explore the genetic basis for a child suspected for hypokalemic periodic paralysis.@*METHODS@#Clinical data of the patient was collected, and venous blood samples were taken from the patient and his parents for the extraction of genomic DNA. Next generation sequencing (NGS) with target capture was carried out to detect potential variants. Suspected variants were validated by Sanger sequencing.@*RESULTS@#The child developed fatigue without obvious reason at the age of 15. Laboratory test revealed hypokalemia but normal serum magnesium. Genetic testing discovered that he has carried two variants in the SLC12A3 gene, namely c.179C>T and c.539C>A. The patient was diagnosed with Gitelman syndrome.@*CONCLUSION@#For children with hypokalemia, genetic testing should be considered for the differential diagnosis of Gitelman syndrome from hypokalemia due to other causes.
ABSTRACT
OBJECTIVE@#To investigate the clinical and genetic features of a Chinese girl featuring mental retardation, intellectual disability, language development delay and epilepsy.@*METHODS@#G-banded chromosomal karyotyping was carried out for the child. Genomic DNA of the patient and her parents was extracted and subjected to high-throughput sequencing. The results were analyzed with bioinformatic tools and validated by Sanger sequencing.@*RESULTS@#The karyotype of the child was ascertained as 46,XX. Sequencing result showed that she has carried a de novo heterozygous c.1861C>T (p.R621X) variant of the SYNGAP1 gene.@*CONCLUSION@#The nonsense variant c.1861C>T (p.R621X) of the SYNGAP1 gene probably underlies the disease in this child. Above result has enabled genetic diagnosis and counseling for her family.
ABSTRACT
OBJECTIVE@#To explore the genetic basis of a Chinese patient featuring global developmental delay.@*METHODS@#Peripheral venous blood samples from the proband and his parents and sister were taken for the extraction of DNA. Target capture and next generation sequencing was carried out to detect genetic variants associated with the disease. Suspected variant was validated by Sanger sequencing.@*RESULTS@#Genetic testing discovered that the proband has carried hemizygous c.150G>T and c.150+1G>T variants of the KDM5C gene which are inherited from his mother. His younger sister also carried the variants. The c.150+1G>A variant was unreported previously, which has altered a splice site and was predicted to be pathogenic by bioinformatics analysis.@*CONCLUSION@#The hemizygous c.150+1G>T variant of the KDM5C gene, known to underlie X-linked Claes-Jensen type syndromic mental retardation, probably accounts for the disorder in the patient. Identification of this variant has enriched the variant spectrum of the KDM5C gene.
ABSTRACT
OBJECTIVE@#To explore the genetic basis for a child featuring short stature.@*METHODS@#G-banded karyotyping, chromosomal microarray analysis (CMA) and high-throughput sequencing were carried out on peripheral blood sample from the child.@*RESULTS@#The karyotype of the child was ascertained as 45,XY,-4[3]/46,XY,r(4)(p16q35)[84]/47,XY,-4,r(4)(p16q25)*2[7]/48,XY,-4,r(4)(p16q35)*3[1]/46,XY,dic r(4;4)(p16q35;p16q35)[2]/46,XY,add(4)(p16)[3]. A 647 kb deletion at 4p16.3 was identified by CMA, which encompassed 6 OMIM genes including ZNF141, PIGG, PDE6B, ATP5I, PCGF3 and MYL5. High-throughput sequencing has identified no pathogenic/likely pathogenic variants consistent with the clinical symptoms.@*CONCLUSION@#A rare ring chromosome 4 syndrome was identified by combined chromosomal karyotyping, CMA and high-throughput sequencing. Conventional cytogenetic analysis and genetic testing in combine have enabled the diagnosis in this case.
ABSTRACT
Objective@#To explore the genetic basis of a patient featuring global developmental delay, intellectual disability, cleft palate, seizures and hypotonia.@*Methods@#Clinical examination and laboratory tests were carried out. Peripheral blood samples were obtained from the patient and his parents. Whole genomic DNA was extracted and subjected to next generation sequencing. Candidate variation was analyzed by using bioinformatic software and validated by Sanger sequencing.@*Results@#The proband was found to carry a heterozygous c. 2117T>C (p.Leu706Pro) variant of the NEDD4L gene, which was a de novo variant validated by Sanger sequencing and predicted to be likely pathogenic according to the American College of Medical Genetics Guidelines.@*Conclusion@#The heterozygous variant of c. 2117T>C (p.Leu706Pro) of the NEDD4L gene probably underlies the disorders in the patient.
ABSTRACT
OBJECTIVE@#To explore the genetic basis of a patient featuring global developmental delay, intellectual disability, cleft palate, seizures and hypotonia.@*METHODS@#Clinical examination and laboratory tests were carried out. Peripheral blood samples were obtained from the patient and his parents. Whole genomic DNA was extracted and subjected to next generation sequencing. Candidate variation was analyzed by using bioinformatic software and validated by Sanger sequencing.@*RESULTS@#The proband was found to carry a heterozygous c.2117T>C (p.Leu706Pro) variant of the NEDD4L gene, which was a de novo variant validated by Sanger sequencing and predicted to be likely pathogenic according to the American College of Medical Genetics Guidelines.@*CONCLUSION@#The heterozygous variant of c.2117T>C (p.Leu706Pro) of the NEDD4L gene probably underlies the disorders in the patient.
Subject(s)
Humans , Male , Genetic Testing , Heterozygote , Intellectual Disability , Genetics , Mutation , Nedd4 Ubiquitin Protein Ligases , Genetics , Periventricular Nodular Heterotopia , GeneticsABSTRACT
OBJECTIVE@#To explore the genetic etiology of a girl featuring epilepsy, speech delay and mild mental retardation.@*METHODS@#Peripheral blood samples of the child and her parents were collected. Genomic DNA was extracted and subjected to next generation sequencing. Suspected variant was confirmed by Sanger sequencing.@*RESULTS@#The child was found to carry a de novo heterozygous c.3592G>A (p.V1198M) variant of the SMARCA2 gene, which was predicted to be pathogenic by bioinformatic analysis.@*CONCLUSION@#The child was diagnosed with Nicolaides-Baraitser syndrome due to heterozygous variant of the SMARCA2 gene.
ABSTRACT
OBJECTIVE@#To explore the genetic basis for a neonate featuring global developmental delay.@*METHODS@#Clinical and laboratory tests were carried out for the patient. Peripheral venous blood samples were collected from the neonate and his parents for the extraction of DNA. Potential variant was detected by using targeted capture and next generation sequencing for a panel of genes associated with nervous system diseases. Suspected variant was validated by Sanger sequencing.@*RESULTS@#The nine-month-old boy manifested global developmental delay and was unstable to sit alone and distinguish strangers from acquaintance. Genetic testing revealed two novel variants of the SLC19A3 gene in him, namely c.448G>A and c.169C>T. The amino acids encoded by the two codons are highly conservative, and both variants were predicted to be pathogenic by bioinformatic analysis.@*CONCLUSION@#The compound heterozygous c.448G>A and c.169C>T variants probably underlay the onset of disease in the patient. Above finding also enriched the variant spectrum of SLC19A3 gene underlying Biotin-thiamine responsive basal ganglia disease.