Whole exome sequencing analysis and prenatal diagnosis for a Chinese pedigree affected with microphthalmia / 中华医学遗传学杂志

OBJECTIVE@#To analyze clinical features and genetic cause for a Chinese pedigree affected with microphthalmia.@*METHODS@#The proband and his parents were subjected to whole exome sequencing (WES) to identify potential pathogenic variants. Sanger sequencing was carried out to confirm the result of WES in available members from the pedigree. Prenatal diagnosis was provided to the proband's mother by genetic testing of amnionic DNA.@*RESULTS@#A heterozygous nonsense mutation c.289C>T (p.R97*) was identified in the OTX2 gene among three patients from the pedigree by WES. The result was confirmed by Sanger sequencing. The proband's mother has carried the same mutation but did not have microphthalmia. The proband's father, aunt and the mother's fetus did not carry the mutation.@*CONCLUSION@#The c.289C>T (p.R97*) mutation probably underlies the microphthalmia in this pedigree. Above result has facilitated genetic counseling and prenatal diagnosis.

Prenatal diagnosis of a fetus with cleft lip and palate by using chromosomal microarray analysis / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with cleft lip and palate.@*METHODS@#Copy number variations (CNVs) in the fetus and his parents were detected with chromosomal microarray analysis (CMA).@*RESULTS@#As revealed by the CMA assay, the fetus has carried a 228 kb deletion in Xp11.22 region and a 721 kb duplication in 9p21.1. Both CNVs were inherited from the parents. The CNV in Xp11.22 was predicted to be pathogenic by involving the PHF8 gene, whilst the CNV in 9p21.1 was predicted to be benign.@*CONCLUSION@#Deletion of the Xp11.22 region probably underlies the cleft lip and palate in this fetus.

Norrie disease caused by a c. 361C>T missense variant of the NDP gene in a pedigree / 中华医学遗传学杂志

Objective@#To explore the genetic etiology of a pedigree affected with Norrie disease.@*Methods@#Four individuals from the core family of the proband were subjected to whole exome sequencing in order to identify the pathological variant. Sanger sequencing was used to verify the finding among 7 additional members from the pedigree.@*Results@#The proband and other 3 male patients have all carried a hemizygote c. 361C>T (p.Arg121Trp) missense variant of the NDP gene, for which his mother, grandmother and two younger female cousins were heterozygous carriers. The same variant was not detected among unaffected males. Above results conformed to a X-linked recessive pattern of inheritance.@*Conclusion@#The missense variant c. 361C>T of the NDP gene probably underlies the Norrie disease in this pedigree.

Norrie disease caused by a c.361C>T missense variant of the NDP gene in a pedigree / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a pedigree affected with Norrie disease.@*METHODS@#Four individuals from the core family of the proband were subjected to whole exome sequencing in order to identify the pathological variant. Sanger sequencing was used to verify the finding among 7 additional members from the pedigree.@*RESULTS@#The proband and other 3 male patients have all carried a hemizygote c.361C>T (p.Arg121Trp) missense variant of the NDP gene, for which his mother, grandmother and two younger female cousins were heterozygous carriers. The same variant was not detected among unaffected males. Above results conformed to a X-linked recessive pattern of inheritance.@*CONCLUSION@#The missense variant c.361C>T of the NDP gene probably underlies the Norrie disease in this pedigree.

Clonal origin analysis of the tumor cells in multifocal papillary thyroid carcinoma with Hashimoto's thyroiditis / 中华普通外科杂志

Objective To investigate the relationship between Hashimoto thyroiditis (HT) and thyroid papillary carcinoma (PTC) by analyzing the expression of BRAF V600E mutation and (N-,H-,K-) RAS codons 12,13 and 61 mutants in cases of multifocal PTC with HT.Methods 80 tumor samples in 37 multifocal PTC with HT cases,were analyzed for the genotypic changes of BRAF V600E,as well as the (N-,H-,K-)RAS codons 12,13 and 61 mutants by DNA sequencing assay and amplification refractory mutation system (ARMS).Results BRAF V600E mutation was detected in 51 samples and RAS gene mutations was found in 3 samples (N-RAS codon 61 mutant in 2 samples and H-RAS codon 61 mutant in 1 sample).Different clonal origin was present in 20 cases of multifocal PTC with HT (54.1％,20/37).There was no statistical significance (P ＞ 0.05) in the incidence of the difference in the origin of tumor cells,compared with the results (61.7％,37/60) of multifocal PTC without HT in the related literature.Conclusion In more than half of multifocal PTC with HT cases,the tumor cells originate from different clones.Our results do not support the opinion that HT predisposes patients to develop PTC,because HT does not have a significant effect on expression of BRAF and RAS gene mutation in PTC,accordingly HT is more likely to be a part of the host tumor immune response system.

The diagnostic value of computed tomography histogram analysis in thyroid malignant solitary nodules showing coarse calcifications / 中华内分泌外科杂志

Objective To investigate the diagnostic value of computed tomography (CT) histogram analysis for thyroid malignant solitary coarse calcification nodules (MSCN).Methods A total of 89 thyroid solitary coarse calcification nodules (coarse calcification ≥5 mm,no definite soft tissue around calcification) confirmed either by surgery or histopathological examination in 86 patients enrolled in this study from Jan.2009 to Dec.2015 were evaluated,including 33 MSCN from 32 patients and 56 benign solitary coarse calcification nodules (BSCN) from 56 patients.Overall,27 cut-off values were calculated by N (4 ≤ N ≤ 30) times of 50 Hounsfield units (HU) in the range of 200 HU to 1500 HU,and each cut-off value and the differences in the corresponding area percentages in the CT histogram were recorded for MSCN and BSCN.The optimal cut-off value and the corresponding area percentage were established by receiver operating characteristic (ROC) curve analysis.Results In the 24 groups with an ROC area under the curve (AUC) of more than 0.7,at a cut-off value of 1150 HU and at an area percentage of no less than 98.4％,the ROC AUC reached a maximum of 0.86,and the accuracy,sensitivity,and specificity were 70.8％,93.9％,and 57.1％,respectively.At a cut-off value of 450 HU and at an area percentage of no less than 46.3％,the accuracy,sensitivity,and specificity were 76.4％,48.5％,and 92.9％,respectively.At a cut-off value of 550 HU and at an area percentage of no less than 81.5％,the accuracy,sensitivity,and specificity were 75.3％,33.3％,and 100％,respectively.Conclusions In comparison with the cut-off value of 1150 HU with an area percentage of no less than 98.4％,the sensitivities for the cut-off value of 450 HU with an area percentage of no less than 46.3％ and for the cut-off value of 550 HU with an area percentage of no less than 81.5％ were lower;however,the specificities increased significantly,providing an important basis for reducing the misdiagnosis of MSCN.

Value of CT hyperenhancement sign in diagnosis and differential diagnosis of benign and malignant nodules in thyroid / 中华内分泌外科杂志

Objective To assess the value of CT hyperenhancement sign in diagnosis and differential diagnosis of benign and malignant thyroid nodules.Methods CT findings of 2926 nodules in 1676 patients were retrospectively analyzed,among which 2174 nodules were benign and 752 nodules were malignant.All the patients had pathological diagnosis.The degrees of enhancement were divided into hyperenhancement and iso/hypoenhancement.The distribution of hyperenhancement in benign and malignant nodules were summarized.The sensitivity,specificity,positive and negative predictive value and accuracy of hyperenhancement for benign nodules and adenomatoid nodules were observed.Results Hyperenhancement was more common in benign nodules than in malignant nodules (10.3％ vs 0.7％,x2 =70.259,P ＜ 0.05),and its sensitivity,specificity,positive and negative predictive value and accuracy was 9.8％,99.5％,98.2％,27.6％ and 32.8％,respectively.Hyperenhancement was more common in adenomatoid nodules than in nonadenomatoid benign nodules (67.4％ vs 6.1％,x2 =525.025,P ＜ 0.05),and its sensitivity,specificity,positive and negative predictive value and accuracy was 67.4％,93.9％,41.6％,97.8％ and 92.3％,respectively.Conclusion Hyperenhancement sign is an important sign which can effectively differentiate benign nodules from malignant nodules,and adenomatoid nodules from nonadenomatoid benign nodules,and it is helpful for diagnosis of benign nodules and adenomatoid nodules.

Expression of caudal related homeodomain transcription 2 in colon cancer and its relationship with metas-tasis / 中华内分泌外科杂志

Objective To study the expression of caudal related homeodomain transcription 2 ( CDX2 ) protein in human colon cancer , and study the relationship between protein expression and colon cancer metasta -sis.Methods With immunohistochemical technique in peroxidase notation , pathological specimens of 80 cases of colon cancer were selected , including 47 cases of distal metastasis , and 33 cases without cancer metastasis . CDX2 protein expression in cancer tissue and the related data were statistically analyzed .Results Patients'sex, age and location of colon tumors had no statistical relation with CDX 2 protein expression(P>0.05).CDX2 pro-tein was statistically different in well-differentiated(100.00%), moderately-differentiated(80.00%), and poor-ly-differentiated(33.33%) tumor tissues.The difference had statistical significance (P<0.05), The expression of CDX2 protein reduced with the reduction in the degree of colorectal adenocarcinoma differentiation , rs =0.217, indicating that CDX2 protein expression was positively correlated with the malignant degree of colon canc -er.Positive CDX2 protein expression was significantly lower in metastatic colon cancer tissues (72.3%) than in non-metastatic tissues ( 90.9%) , and the difference had statistical significance .Lymph node metastasis could down regulate CDX2 protein expression in colorectal cancer .Conclusion CDX2 protein is positively correlated with the differentiation degree of colon cancer and distal metastasis can down regulate CDX 2 protein expression .

The value of CT annular calcification in identifying benign and malignant thyroid nodules / 中华放射学杂志

Objective To evaluate the value of annular calcification in CT in the diagnosis and differential diagnosis for benign and malignant thyroid nodules.Methods CT findings of 67 nodules in 67 patients pathologically diagnosed with annular calcifications were retrospectively analyzed to identify 49 benign nodules and 18 malignant nodules.The interior or boundaries of annular calcification before and after contrast-enhancement were compared,and the degree of enhancements of both interior annular calcification and thyroid tissues were observed.After contrast-enhancement,the numbers of lesions showing clearer boundaries and higher degree of enhancement were summarized.Statistic analysis was conducted by using x2 test.Results Among 67 nodules with annular calcifications,clearer boundaries after contrast-enhancement were observed in 61.2％ (30/49) benign nodules and 16.7％ (3/18) malignant nodules,showing significant statistical difference (x2 =10.457,P ＜ 0.05).The sensitivity and specificity of clearer edge after contrast-enhancement for benign nodules were 61.2％ (30/49) and 83.3％ (15/18) respectively.Higher degree of enhancement were observed in 16.3％ (8/49) in benign nodules and 0(0/18) malignant nodules,showing no significant statistical difference (x2 =3.337,P ＞ 0.05).The sensitivity and specificity of higher degree of enhancement for benign nodules were 16.3％ (8/49) and 100.0％ (18/18) respectively.The combination of clearer boundaries and higher degree of enhancement after contrast-enhancement was observed in 77.6％ (38/49) benign nodules and 16.7％ (3/18) malignant nodules,showing significant statistical difference (x2 =20.549,P ＜ 0.05).Meanwhile,the sensitivity and specificity of such combination for benign nodules were 77.6％ (38/49) and 83.3％ (15/18) respectively.Conclusions CT is important in the diagnosis of thyroid nodules with annular calcification.Clearer boundary after contrast-enhancement and its combination with higher degree of enhancement are helpful for the diagnosis of benign nodules.Boundaries that similar to or more obscure than that of plain scan indicate malignant nodules.

Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated glial-derived neurotrophic factor combined with early rehabilitation training / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Spinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.</p><p><b>METHODS</b>SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups: natural healing group, gene therapy group, rehabilitation training group, and combination therapy group (gene therapy in combination with rehabilitation training). Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma.</p><p><b>RESULTS</b>The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.</p><p><b>CONCLUSION</b>These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.</p>