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OBJECTIVE@#To explore the clinical phenotype and genetic basis for a Chinese pedigree affected with Oral-facial-digital syndrome type I (OFD1).@*METHODS@#A pedigree with OFD1 who presented at Hebei General Hospital on March 17, 2021 was selected as the subject. Clinical data of the child was collected. Trio-whole exome sequencing (trio-WES) was carried out for the proband and members of her pedigree, and candidate variant was verified by Sanger sequencing.@*RESULTS@#The proband has featured hypotelorism, broad nasal root, flat nasal tip, lobulated tongue, tongue neoplasia, camptodactyly of left fifth finger, syndactyly of right fourth and fifth fingers, and delayed intellectual and language development. Trio-WES revealed that the proband and her daughter, sister and mother have harbored a heterozygous c.224A>G (p.Asn75Ser) variant of the OFD1 gene. The same variant was not found among healthy members from her pedigree.@*CONCLUSION@#The c.224A>G (p.Asn75Ser) variant probably underlay the OFD1 in this pedigree. Above discovery has enriched the spectrum of OFD1 gene variants.
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Humanos , Femenino , Linaje , Síndromes Orofaciodigitales/genética , Pueblos del Este de Asia , Fenotipo , Heterocigoto , Mutación , ChinaRESUMEN
This paper reported the genetic analysis of a pedigree in which three affected fetuses with short limbs were revealed by first-trimester ultrasonography in three consecutive pregnancies. Tissues of the second aborted fetus were collected and analyzed by chromosome karyotype analysis and whole exome sequencing. The results indicated compound heterozygous mutations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene. Real-time fluorescence quantitative polymerase chain reaction and Sanger sequencing further confirmed that the two variants were inherited from the father and the mother with normal phenotypes, respectively. EX64-EX83 Del was a likely pathogenic variant and c.8190G>T was a variant of uncertain significance. Based on the above results and the medical history, it was highly suspected that the fetus had autosomal recessive short rib polydactyly syndrome type Ⅲ caused by compound heterozygous variants. Real-time fluorescent quantitative polymerase chain reaction and Sanger sequencing results of the third aborted fetus were consistent with the second fetus. Given the same phenotypes of fetuses in the second and third pregnancy, it was strongly suggested that the heterozygous variations of EX64-EX83 Del and c.8190G>T in the DYNC2H1 gene were the pathogenic variants in this pedigree.
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Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.
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Objective To assess the value of apparent diffusion coefficient (ADC)map with low b-value to monitor the ablated tissue after high-intensity focused ultrasonic (HIFU)treatment for uterine fibroids.Methods 25 patients with 34 uterine fibroids were treated with HIFU.All patients underwent the routine MRI scans (including pre-and post-contrast scanning)and monoexponential model DWI with b values of 150,600 and 1 000 s/mm2 before the surgery and within 24 hours after the surgery.The mean ADC values with different b-values of the ablated and non-ablated tissues between pre-and post-treatment were analyzed by one-way ANOVA test.The consistency of the ablation area between ADC maps with different b-values and contrast enhancement MRI were evaluated. Results With the b-value of 150 s/mm2 ,the mean ADC value of the ablated tissue was (1.48±0.27)×10-3 mm2/s,which was less significantly than that of pre-treatment (2.06±0.21)×10-3 mm2/s and non-ablated tissue (1.98±0.23)×10-3 mm2/s (P0.05).A fine consistency of the ADC map with the low b-value (150 s/mm2 )was found with non-perfusion volume on contrast-enhanced T1 WI,which was superior to that with high b-values (600 s/mm2 and 1 000 s/mm2 )(P<0.05).Conclusion ADC map with low b-value (150 s/mm2 )can be used to evaluate the blood-supply changes and ablated volume of uterine fibroids indirectly,which helps to assess the treatment effect of HIFU.
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Objective To observe the bone metabolism of psoriatic arthritis (PsA) and investigate the roles of some bone metabolism markers such as tartrate-resistant acid phosphatase 5b (TRACP5),C-terminal telopeptide of collagen-Ⅰ (CTX-Ⅰ) and BALP in PsA patients with bone destructions.Methods Sixty-five cases of psoriatic arthritis,30 cases of psoriasis and 30 cases of healthy people were enrolled.Bone mineral densities of lumbar spines and the left femoral necks were measured for all PsA patients using dual energy X-ray absorptiometry.The Serum levels of TRACP5b,CTX-Ⅰ,BALP of healthy controls,Ps and PsA patients were measured.The PsA group was further divided into bone destruction group and none bone destruction group by image datasets.The levels of TRACP5b,CTX-Ⅰ,BALP,PsAJAI,ESR and CRP from each group were detected.Mann-Whitney and x2 test were used for statistic analysis.Results TRACP5b levels of the healthy controls,Ps and PsA patients were (0.9±0.4),(0.7±0.5) and (2.0±1.4) U/L respectively,and were significantly higher in the PsA patients than those of the other two groups (Z=-3.698,-3.638; P＜0.05).The CTX-Ⅰ levels of these three groups were (0.9±0.8),(0.6±0.7) and (2.6±1.8) ng/ml respectively,and were also dramatically higher in the PsA patients than the other two groups (Z=-5.262,-5.734; P＜0.05).BALP levels of each group were (22±4),(22±4) and (25±7) U/L,and were also evidently higher in the PsA patients than patients in the other two groups (Z=-2.214,-2.000; P＜0.05).Meanwhile,the levels of TRACP5b [(2.6±1.4) U/L],CTX-Ⅰ [(3.1±1.8) ng/ml] and BALP [(26±7) U/L] were significantly higher in bone destruction group than those in the none bone destruction group [(1.2±1.0) U/L,(1.9±1.6) ng/ml,(23±6) U/L,Z=-3.544,-3.429,-2.083; P＜0.05].Conclusion The high levels of TRACP5b,CTX-Ⅰ and BALP in PsA indicate that there is bone metabolism imbalances in PsA.And the high levels of TRACP5b,CTX-Ⅰ and BALP in the bone destruction group suggest that the rises of TRACP5,CTX-Ⅰ and BALP levels may be related with bone erosions.
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ObjectiveTo explore the effect of osteoclasts and osteoprotegerin/receptor activator of nuclear factor-kappa B ligand (OPG/RANKL) system on bone destruction of psoriatic arthritis.MethodsThe peripheral blood mononuclear cells from 41 psoriatic arthritis (PsA) patients,20 osteoarthritis (OA) patients and 24 healthy controls were cultured to become osteoclasts.After 14 days,cytochemistry method was used to detect tartrate-resistant acid phosphatase (TRAP) expression.At the same time,enzyme-linked immuno sorbent assay(ELISA) was used to measure the levels of serum OPG and RNAKL for all cases.At the same time,the clinical and laboratory examinations of the PsA were collected.Statistical analysis was conducted with one-way ANOVA and Spearman's correlation.ResultsSignificantly higher OC production was observed in the peripheral blood of PsA patients[(17.7±4.8)/view field] than that of the healthy controls[(6.4±1.6)/view field] and OA patients [(6.5±l.6)/view field].The levels of RANKL were significantly higher in PsA patients [(178±38) pg/ml] than those in the other two groups [(32±4) pg/ml and (67±17) pg/ml].There was significant difference between the PsA group with bone destruction and without destruction in the levels of OC and RANKL [(17.6±0.9) /view vs(7.9±1.3) /view and(199±72) pg/ml vs(128±44) pg/ml,P＜0.01].Imaging scores was positively correlated with the levels of OC and RANKL in PsA patients (P＜0.05).ConclusionIn PsA,there are significantly more OC and higher RANKL in the peripheral blood than those of the controls.The high levels of OC and RANKL are closely related with bone destruction.OC and RANKL are useful in identifying bone destruction.