The application of unilateral biportal endoscopy through extraforaminal approach in the treatment of extra canal lumbosacral nerve root entrapment / 中华骨科杂志

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.

Clinical characteristics and genetic analysis of two children with Autosomal dominant mental retardation type 21 due to variants of CTCF gene / 中华医学遗传学杂志

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.

Diagnosis of a case with Hermansky-Pudlak syndrome type 5 through high-throughput sequencing and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a patient with Hermansky-Pudlak syndrome type 5 (HPS-5).@*METHODS@#A child with HPS-5 who had attended the Children's Hospital Affiliated to Shandong University on October 3, 2019 was selected as the study subject. Clinical data of the child were collected. Genetic variant was analyzed through high-throughput sequencing. A literature review was also carried out.@*RESULTS@#The child, a 1-year-and-5-month-old girl, had nystagmus since childhood, lost of retinal pigmentation by fundus examination and easy bruising. High-throughput sequencing revealed that she has harbored compound heterozygous variants of the HPS5 gene, namely c.1562_1563delAA (p.F521Sfs*27) and c.1404C>A (p.C468X), which were inherited from his father and mother, respectively. Based on the guidelines from the American College for Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS+PM2_Supporting+PM3+PP4). Among 18 previously reported HPS-5 patients, all had had eye problems, and most of them had tendency for bleeding. Eight cases had carried compound heterozygous variants of the HPS5 gene, 8 carried homozygous variants, 2 carried double homozygous variants, and most of them were null mutations.@*CONCLUSION@#The c.1562_1563delAA(p.F521Sfs*27) and c.1404C>A (p.C468X) compound heterozygous variants of the HPS5 gene probably underlay the HPS-5 in this child. High-throughput sequencing has provided an important tool for the diagnosis. HSP-5 patients usually have typical ocular albinism and/or oculocutaneous albinism and tendency of bleeding, which are commonly caused by compound heterozygous and homozygous variants of the HPS5 gene, though serious complications have been rare.

Clinical and ASS1 gene variant analysis of three Chinese pedigrees affected with Citrullinemia type I / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Citrullinemia type I (CTLN1).@*METHODS@#Three children diagnosed at the Children's Hospital Affiliated to Shandong University from 2017 to 2020 were selected as the study subjects. Genomic DNA was extracted from peripheral blood samples of the probands and their parents. Next generation sequencing (NGS) was carried out to detect pathological variants of the probands. Sanger sequencing was used for validating the candidate variant among the pedigrees.@*RESULTS@#The probands have respectively carried compound heterozygous variants of c.207_209delGGA and c.1168G>A, c.349G>A and c.364-1G>A, c.470G>A and c.970G>A of the ASS1 gene, which were respectively inherited from their parents.@*CONCLUSION@#The newly discovered c.207_209delGGA and c.364-1G>A variants have enriched the mutational spectrum of the ASS1 gene. And the mutation spectrum of Chinese CTLN1 patients is heterogeneous.

Clinical and genetic analysis of a very early-onset inflammatory bowel disease type 28 child with atypical clinical manifestation / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations.@*METHODS@#A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2_Supporting+PP3).@*CONCLUSION@#The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.

Analysis of CNNM2 gene variant in a child with Hypomagnesemia, seizures, and mental retardation syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a child with Hypomagnesemia, epilepsy and mental retardation syndrome (HSMR).@*METHODS@#A child who was admitted to the Children's Hospital of Shandong University on July 9, 2021 due to repeated convulsions for 2 months was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 1-year-and-7-month-old male, had presented with epilepsy and global developmental delay. Serological testing revealed that he has low serum magnesium. Genetic testing showed that the child has harbored a heterozygous c.1448delT (p.Val483GlyfsTer29) variant of the CNNM2 gene, which was de novo in origin. The variant has caused substitution of the Valine at position 483 by Glycine and formation of a termination codon after 29 amino acids at downstream. As predicted by Swiss-Model online software, the variant may alter the protein structure, resulting in a truncation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1448delT (p.Val483GlyfsTer29) was predicted as a pathogenic variant (PVS1+PS2+PM2_Supporting+PP4).@*CONCLUSION@#The heterozygous c.1448delT variant of the CNNM2 gene probably underlay the HSMR in this child. Above finding has enriched the phenotype-genotype spectrum of the CNNM2 gene.

Repair of defects after lumbar discectomy with autologous bone marrow mesenchymal stem cells and annular suture / 中华骨科杂志

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.

Microscope-assisted minimally invasive anterior lumbar discectomy and zero-profile fusion for lumbar degenerative diseases / 中华骨科杂志

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.

Analysis of ADNP gene variant in a child with Helsmoortel-van der Aa syndrome / 中华医学遗传学杂志

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.

Analysis of a case with Mowat-Wilson syndrome caused by ZEB2 gene variant / 中华医学遗传学杂志

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.

Clinical and genetic analysis of a patient with slow-channel congenital myasthenic syndrome / 中华医学遗传学杂志

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.

Clinical and genetic analysis of a patient with Gitelman syndrome misdiagnosed as hypokalemic periodic paralysis / 中华医学遗传学杂志

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.

A case with autosomal dominant mental retardation type 5 due to de novo SYNGAP1 variant / 中华医学遗传学杂志

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.

Clinical phenotype and genetic analysis of a Chinese patient featuring X-linked Claes-Jensen type syndromic mental retardation / 中华医学遗传学杂志

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.

Analysis of clinical and genetic characteristics of a child with ring chromosome 4 syndrome / 中华医学遗传学杂志

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.

Clinical and genetic analysis of an infant with 3-methylglutaconic aciduria type VII / 中华医学遗传学杂志

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.

Clinical and genetic analysis of a patient with periventricular nodular heterotopia 7 caused by NEDD4L gene variant / 中华医学遗传学杂志

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.

Clinical and genetic analysis of a case with Nicolaides-Baraitser syndrome / 中华医学遗传学杂志

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.

Identification of two novel SLC19A3 variants in a Chinese patient with Biotin-thiamine responsive basal ganglia disease / 中华医学遗传学杂志

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.

Clinical and genetic analysis of a patient with periventricular nodular heterotopia 7 caused by NEDD4L gene variant / 中华医学遗传学杂志

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.