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Bone age is a quantitative representation of the skeletal development pattern.X-ray imaging of the wrist with the Greulich-Pyle method is commonly used to assess bone age in clinic.In adolescent children, the sensitivity and specificity of the the Greulich-Pyle method are not sufficient because the bones of the wrist are already mature.In contrast, epiphyseal morphological changes in the knee joint throughout adolescence can provide information for the assessment of bone age in adolescent children, and the feasibility of knee joint bone age assessment has been verified.With the application of artificial intelligence (AI) in the medical field, the accuracy of AI interpretation of bone age is also recognized.One of the important uses of bone age assessment in adolescent children is to predict the remaining growth potential.Based on knee images, exploring the use of AI to build a model for predicting residual growth potential is a more meaningful research direction for clinical purposes.This paper reviews the anatomical characteristics of the knee joint, the application of knee joint imaging and the research progress of AI in bone age assessment.
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OBJECTIVE@#To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene.@*METHODS@#Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature.@*RESULTS@#The patient was found to harbor a heterozygous c.601C>T (p.Arg201*) nonsense variant of the PSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed.@*CONCLUSION@#Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.
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Child , Humans , China , Dwarfism , Genetic Testing , Heterozygote , SyndromeABSTRACT
Objective:To analyze the association between the expression of ubiquinone oxidoreductase complex assembly factor 4 (NDUFAF4) and clinical prognosis of patients with hepatocellular carcinoma (HCC), evaluate the effect of NDUFAF4 on the radiosensitivity of human HCC cell lines, and unravel the underlying mechanism.Methods:The online database and HCC tissue samples were used to investigate the expression of NDUFAF4, and the correlation between NDUFAF4 expression level and clinical prognosis. The si-NDUFAF4 plasmid which down-regulated the expression level of NDUFAF4 was transferred into HepG2 and Huh7 cells. The radiosensitivity of HCC cell lines was detected by clone formation experiment. Nude mice were prepared for tumor-bearing experiment. The β-catenin level was detected by immunofluorescent staining. The expression levels of E-cadherin and N-cadherin proteins were determined by Western blot.Results:Bioinformatics results confirmed that NDUFAF4 was significantly up-regulated in HCC tissues, and the higher the expression level, the worse the patients' clinical prognosis ( P<0.05). The expression level of NDUFAF4 in HCC tissues was significantly higher than that in the adjacent tissues. Clone formation experiment confirmed that knockdown of NDUFAF4 significantly decreased the survival rate of HCC cells ( P<0.01). In vivo experiment showed that knockdown of NDUFAF4 could prevent the proliferation of HCC cells and down-regualte the expression levels of β-catenin and Ki-67. Knockdown of NDUFAF4 significantly down-regulated the expression level of β-catenin protein in the nucleus of HCC cell lines, suggesting that NDUFAF4 could activate the WNT/β-catenin signaling pathway. Knockdown of NDUFAF4 significantly up-regulated the expression level of E-cadherin and down-regulated that of N-cadherin. Conclusions:Knockdown of NDUFAF4 can significantly enhance the radiosensitivity of HCC cell lines by inhibiting the WNT/β-catenin signaling pathway. The expression level of NDUFAF4 is intimately correlated with clinical prognosis. NDUFAF4 can be considered as a new target for lowering the radiation resistance of HCC.
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Objective:To observe the clearance strategies of hemiplegic stroke survivors with foot drop.Methods:Thirty hemiplegic stroke survivors with foot drop formed the observation group and 30 healthy counterparts constituted the control group. A three-dimensional motion capture system was used to observe and compare the minimum toe clearance (MTC) and its variability between the two groups to draw the motion trajectory of the toe in the swing phase of their gaits. The gait parameters were correlated with the toe clearance.Results:The average MTC of the observation group subjects on both the hemiplegic and non-hemiplegic side (12.01±3.36 and 22.38±5.51mm) was significantly smaller than the control group′s averages. The variability of their MTCs on both sides was also significantly greater. Clearance on the hemiplegic side was significantly less and its variability was significantly greater. Among the observation group, MTC on the hemiplegic side was positively correlated with walking speed, step length, swing phase percentage, maximum angle of hip extension, maximum angle of knee flexion, maximum angle of ankle dorsiflexion, and the range of motion of the knee and ankle joints.Conclusions:Hemiplegic stroke survivors with foot drop walk unstably with little toe clearance. It is necessary to intervene at the hip, knee and ankle to improve their obstacle clearance.
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The clinical features and genetic variants of the patient with sitosterolemia who was referred to Shanghai Children′s Medical Center, Shanghai Jiaotong University School of Medicine from June 2019 to January 2020 were retrospectively analyzed.The patient was treated with Ezetimibe tablets combined with diet control, and the follow-up was performed regularly.Besides, a relevant literature review was conducted.A 7-year and 5-month-old boy was referred to the hospital for " repeated thrombocytopenia for 7 months" with normal serum cholesterol.The whole exome sequencing showed that compound heterozygous mutations (p.Arg446*, p.Gln251*) in ABCG5 gene were inherited from their parents respectively.Hence, he was diagnosed with sitosterolemia.After 29 days of treatment with Ezetimibe tablets combined with diet control, the patient′s platelets returned to normal values without obvious adverse reactions related to drugs.Children with sitosterolemia may present with rare thrombocytopenia, and the therapeutic effects of Ezetimibe tablets combined with diet control are favorable.
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Alstr?m syndrome is a rare multisystem genetic disease caused by mutations in the ALMS1 gene.Both of its clinical diagnosis and treatment are very difficult.In 2020, the Consensus Clinical Management Guidelines for Alstr?m Syndrome, developed with the participation of many countries, was published in the Orphanet Journal of Rare Diseases.A systematic literature review on Alstr?m syndrome of the last 45 years until October 2019 was carried out and then the clinical management guideline for Alstr?m syndrome was proposed.In this report, the contents of the 2020 European guideline for Alstr?m syndrome would be introduced briefly with appropriate interpretation in order to provide reference.
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The clinical data of a case of diabetic ketoacidosis with FOXP3 mutation identified by genetic test were collected and summarized. The follow-up results and clinical characteristics of 18 months after hematopoietic stem cell transplantation were analyzed. The male patient was 3 years and 5 months old. At the age of 5 months, the patient was diagnosed as diabetic ketoacidosis due to mental malaise and vomiting, followed by severe diarrhea, repeated eczema, and nephrotic syndrome, which was confirmed as IPEX syndrome due to FOXP3 gene mutation by genetic test. In August 2018, hematopoietic stem cell transplantation was carried out in the Hematology Department of our hospital. During 18 months of follow-up, the patients′ autoimmune status was ameliorated, no new autoimmune diseases appeared, the blood glucose control was significantly improved, and the insulin dosage was significantly reduced.
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OBJECTIVE@#To explore the clinical and genetic characteristics of a child with frontometaphyseal dysplasia 1 (FMD1) due to variant of FLNA gene.@*METHODS@#Clinical phenotype of the patient was analyzed. Whole exome sequencing (WES) was carried out to detect pathogenic genetic variants. Sanger sequencing was used to verify the result in his parents.@*RESULTS@#The 2-year-and-9-month-old boy presented with facial dysmorphism (supraorbital hyperostosis, down-slanting palpebral fissure and ocular hypertelorism), skeletal deformities (bowed lower limbs, right genu valgum, left genu varus, slight deformity of index and middle fingers, and flexion contracture of little fingers). He also had limited left elbow movement. High-throughput sequencing revealed that he has carried a de novo heterogeneous c.3527G>A (p.Gly1176Glu) missense variant of the FLNA gene. The same variant was found in neither parent.@*CONCLUSION@#The clinical manifestations of FMD1 such as joint contracture and bone dysplasia can occur in infancy and deteriorate with age, and require long-term follow-up and treatment. Above finding has expanded the spectrum of FLNA gene variants.
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Child , Humans , Infant , Male , Filamins/genetics , Forehead/abnormalities , Osteochondrodysplasias/genetics , Phenotype , Exome SequencingABSTRACT
OBJECTIVE@#To explore the genetic basis for 7 patients with Alström syndrome.@*METHODS@#DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4).@*CONCLUSION@#ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.
Subject(s)
Humans , Alstrom Syndrome/genetics , Cell Cycle Proteins/genetics , Mutation , Pedigree , Exome SequencingABSTRACT
Congenital disorders of glycosylation(CDG)are a group of rare inherited metabolic diseases due to defects in the glycosylation of glycoproteins and/or glycolipids.Most of them are autosomal recessive and have multisystemic manifestations, which is characterized by dysmorphic facial features, developmental delay, growth failure, hypotonia, neurological abnormalities, hypoglycemia and multisystem disfunctions.Isoelectrofocusing(IEF)analysis of transferrin(Tf)and mass spectrometry(MS)technology can diagnose some subtypes of CDG, while many currently rely on genomic sequencing technology for diagnosis.A few subtypes can be clinically relieved or even cured by treatment, but most have no effective treatment.Development of molecular, biochemical and facial recognition techniques may deepen our understanding of this disease.
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OBJECTIVE@#To explore the clinical characteristics and genetic basis for an infant featuring combined pituitary hormone deficiency.@*METHODS@#Clinical data and results of DNA sequencing of the child were analyzed.@*RESULTS@#The 10-month-old male infant presented with recurrent hypoglycemia, extremely poor appetite and constipation, and severe growth retardation from 2 months on, in addition with pituitary hormone deficiency involving growth hormone, thyroid stimulating hormone, and prolactin. Next generation sequencing revealed a novel heterozygous c.767-769del (p.Glu256del) variant of the POU1F1 gene in the patient.@*CONCLUSION@#The patient was diagnosed with combined pituitary hormone deficiency due to the POU1F1 gene variant, for which replacement therapy including thyroxine and growth hormone was provided. Hypoglycemia is unusual in patients carrying POU1F1 gene variants and requires close attention in clinical practice. For children with multiple pituitary hormone deficiency, genetic testing should be recommended to determine the cause.
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OBJECTIVE@#To analyze the clinical characteristics and genetic variation in a child with acrodysostosis type 2.@*METHODS@#The child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples from him and his parents. High-throughput sequencing was carried out. The result was verified by Sanger sequencing.@*RESULTS@#The 8-year-old boy presented with midface hypoplasia, hypertelorism, prominent nasal bridge, small and upturned nostrils, broad thumb and great toes, and brachydactyly of remaining fingers and toes. Genetic testing revealed that the child has carried a heterozygous c.1813T>C (p.Tyr605His) missense mutation of the PDE4D gene. The same mutation was not found in either parent and was unreported previously.@*CONCLUSION@#The child was diagnosed with acrodysostosis type 2 due to the novel mutation of the PDE4D gene.
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Alstrom syndrome(ALMS)is a rare autosomal recessive disorder involving multiple systems.The main clinical manifestations include nystagmus, hearing loss, obesity, insulin resistance, type 2 diabetes, dilated cardiomyopathy, etc.Primary cilia are key organelles.ALMS is classified as a ciliopathy, mainly related to the mutation of ALMS1 gene which affects cilia function, but the specific mechanism remains unclear.At present, the diagnosis of ALMS mainly relies on clinical manifestations and gene sequencing.There are no specific and effective treatment methods except for symptomatic treatment, but early diagnosis and intervention can delay disease progression and improve patients′ quality of life.This article reviews recent advances in the pathogenesis, diagnosis, and treatment of ALMS.
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Some systemic diseases also can cause changes in thyroid hormone levels in the human body,called the non-thyroidal illness syndrome (NTIS),which occur in both children and adults.NTIS is more common in neonates,surgical patients,patients at intensive care unit and patients with genetic disease patients.Deiodinase activity,hypothalamic-pituitary-thyroid axis,thyroid hormone transporters,serum binding proteins,nuclear thyroid hormone receptors,cytokines,and oxidative stress are factors for developing NTIS.The prognosis of NTIS is often adaptive and self-limiting.The treatment of thyroid hormone supplementation during the disease needs further study.
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Genetic syndromes often involve craniofacial malformations,and certain syndromes are associated with a specific facial pattern such as Down syndrome.With the development of artificial intelligence in the medical field,face recognition technology has been successfully applied in the diagnosis of genetic syndrome,such as Down syndrome,Cornelia de Lange syndrome,22q11.2 deletion syndrome and Noonan syndrome.Some reports suggested that the detection rates of face recognition technology are higher than clinical specialists.In the future,face recognition technology is expected to be applied in the screening of and genetic syndromes,to help the diagnosis and to be applied in scientific research.
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Objective@#To expand the knowledge of the clinical and molecular characteristics of the children with Bloom syndrome.@*Methods@#Clinical data of two siblings with classic Bloom syndrome of Shanghai Children's Medical Center from January 2009 to June 2017 were obtained and analyzed. The DNA of peripheral blood was collected from two Bloom syndrome siblings and their parents during 2015. The mutations were detected with high-throughput sequencing by Illumina sequencing platform.@*Results@#The two siblings (probands) visited our department for short stature and growth retardation, they had full-term normal delivery after normal pregnancy of their mother. Both cases presented with feeding difficulties, malnutrition, microcephaly and mental retardation, repeated infection, symmetrical short stature and special faces. At first, the proband was an 8-year-3-month old girl, her height was 99.7 cm, body mass index (BMI) 12.07 kg/m2, head circumference was 45.5 cm, and birth weight was 1.6 kg. Her younger brother was 3-year-11-month old, his height was 86.6 cm, BMI was 14 kg/m2, birth weight was 1.95 kg, and the head circumference reached 36 cm at 16 months. No evidence of cancer and characteristic rash was detected at 8-year follow-up. Pathogenic complex heterozygous mutations c.772_773delCT, p.Leu258Glufs*7 and c.959+ 2T>A in BLM gene were detected in both siblings, which were separately inherited from their unaffected parents. Besides , c.959 + 2T>A has not been reported previously.@*Conclusions@#Children with Bloom syndrome are characterized by short stature, microcephaly, special faces, feeding difficulties, and immunodeficiency. And butterfly erythematous rash may be absent. The c.959+2T>A mutation detected in our patients maybe a novel pathogenic mutation.
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<p><b>OBJECTIVE</b>To analyze clinical manifestations and genetic mutation in a child with severe short stature and other malformations.</p><p><b>METHODS</b>The child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples of the proband and her family members. Candidate genes were captured with Agilent SureSelect and sequenced on an Illumina platform. Suspected mutation was verified by Sanger sequencing.</p><p><b>RESULTS</b>The patient, a six-year-and-10-month old girl, presented with non-symmetrical short stature, dysmorphism, abnormalities of limbs and spine, amblyopia of left eye, and cataract of right eye, in addition with frequent respiratory infection and micturition. Laboratory testing suggested 25-hydroxy vitamin D deficiency (18.9 ng/mL). Spine X-ray showed multiple malformations with centrums. Her mother also featured short stature (138 cm). Her aunt had short stature (130 cm) and limb-length discrepancy. Her little brother was 2.5 years old, and his height was 81 cm (-3.4 SD). Exome sequencing revealed a heterozygous mutation c.184C to T (p.Arg62Trp) in the proband and her mother. The same mutation was not found in her father and brother.</p><p><b>CONCLUSION</b>The patient was diagnosed with X-linked chondrodysplasia punctata 2. Mutation of the EBP gene probably underlied the disease in this family.</p>
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<p><b>OBJECTIVE</b>To analyze two Chinese pediatric patients with multiple malformations and growth and development delay.</p><p><b>METHODS</b>Both patients were subjected to targeted gene sequencing, and the results were analyzed with Ingenuity Variant Analysis software. Suspected pathogenic variations were verified by Sanger sequencing.</p><p><b>RESULTS</b>High-throughput sequencing showed that both patients have carried heterozygous variants of the CHD7 gene. Patient 1 carried a nonsense mutation in exon 36 (c.7957C>T, p.Arg2653*), while patient 2 carried a nonsense mutation of exon 2 (c.718C>T, p.Gln240*). Sanger sequencing confirmed the above mutations in both patients, while their parents were of wild-type for the corresponding sites, indicating that the two mutations have happened de novo.</p><p><b>CONCLUSION</b>Two patients were diagnosed with CHARGE syndrome by high-throughput sequencing.</p>
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Humans , Infant , Male , CHARGE Syndrome , Genetics , DNA Helicases , Genetics , DNA-Binding Proteins , Genetics , Genetic Testing , High-Throughput Nucleotide Sequencing , MutationABSTRACT
Objective To investigate the clinical phenotype and molecular diagnosis of Noonan syndrome (NS) caused by mutations in SHOC2 gene. Methods The clinical data and gene testing results of one child with NS were analyzed retrospectively. Results This is an 8-month-old infant. Since birth, the boy had feeding and sleeping difficulties, irritability, and growth retardation. The boy had large head circumference, sparse, thin and yellow hair, broad and prominent forehead, flat nose, slightly wide eye distance, and slightly bilateral eye fissure outward tilt, no eyelid ptosis. Echocardiography showed patent foramen ovale,ventricular septum and left ventricular hypertrophy.A novel mutation(De novo)was found in the SHOC2 gene, heterozygous missense mutation c.4A>G, p.Ser2Gly His parents were normal genotypes. According to the clinical characteristics, relevant literature was reviewed. The clinical manifestation of sleep difficulty has not been reported in the NS patients with SHOC2 mutation.Conclusions This is the first domestic reported NS case with SHOC2 mutation.The phenotype is consistent with the foreign reports.Sleep difficulty may be a new phenotype of NS with SHOC2 mutation.
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Objective To analysis the clinical and gene mutation characteristics of hereditary fructose intolerance (HFI). Methods The clinical features and the results of gene testing in the child with HFI and her parents were analyzed retrospectively. Gene sequencing was carried out by high-throughput sequencing and validated by Sanger sequencing. Results The 4-year-3-month old girl had recurrent hypoglycemia episodes and growth retardation. When the condition was stable, the levels of lactic acid and urine micro protein were slightly higher, and the levels of thyroid hormone, cortisol, glycosylated hemoglobin, insulin and C peptide were normal.EEG showed epileptiform activity.Gene sequencing revealed the presence of aldolase B gene(ALDOB) compound heterozygous mutations, a novel splicing mutations (c.325-1G>A) in intron 3 and a frameshift mutation (c. 865delC;p.L289fs*10) in exon 8. Her father carries a frameshift mutation, and her mother carries a splicing mutation. Conclusion The diagnosis of HFI caused by ALDOB mutation can be confirmed by high-throughput sequencing technology.