Isolated ocular colobomas caused by a novel variant of the YAP1 gene / 中华眼底病杂志

Objective:To identify the causative gene and observe the phenotypic characteristics of a family with isolated microphthalmia-anophthalmia-coloboma (MAC).Methods:A retrospective clinical study. One patient (proband) and 3 family members of a family with MAC visited the Henan Eye Hospital from May 2019 to May 2022 were included in the study. The patient's medical history and family history were inquired in detail, and the best corrected visual acuity (BCVA), slit lamp microscope, fundus photography, optical coherence tomography (OCT), ophthalmological B mode ultrasound and axial length (AL) measurement were performed. The peripheral venous blood of the proband, his parents and brother was collected for Trio whole-exome sequencing and pathogenic gene screening. Fluorescence quantitative Polymerase chain reaction was used to verify the suspicious variations. The clinical features of the patient's ocular and systemic also were observed.Results:The proband, male, was 3 years old at the first visit. The horizontal pendular nystagmus was detected in both eyes. Vertical elliptical microcornea and keyhole-shaped iris colobomas were detected in both eyes. The objective refraction at first visit (3 years old) was -4.00 DS/-0.50 DC×105° (OD) and -3.50 DS/-1.25 DC×80° (OS). Refraction and BCVA at 6 years old: -6.50 DS/-2.00 DC×110°→0.05 (OD) and -6.00 DS/-1.50 DC×80°→0.2 (OS). The AL at 4 years and 10 months old was 24.62 mm (OD) and 23.92 mm (OS), respectively. The AL at 5 years and 7 months old was 25.24 mm (OD) and 24.36 mm (OS), respectively. Ultrasonography shows tissue defects in both eyes. Fundus photography showed the inferior choroidal coloboma involving optic disc. OCT showed the optic disc in both eyes was abnormal with colobomas around, and the retinal neurosensory layer in colobomas area was disordered and thin; the retinoschisis was visible in the left eye. The proband's parents and siblings have normal phenotypes. Whole exome sequencing reveals a denovo heterozygous deletion of YAP1 gene: YAP1, chr11: 10280247-102100671, NM_ 001130145, loss 1 (EXON: 6-9). The results of bioinformatics analysis were pathogenic variants. Parents and siblings were of the wild type. Conclusions:Loss of heterozygosity in exons 6-9 of YAP1 gene is the pathogenic variation in this family. It can cause abnormal development of anterior segment, chorioretinal colobomas, deepening of axial myopia, even severe macular colobomas and retinoschisis.

Gene mutation detection of the posterior microphthalmia-retinal pigment degeneration family / 中华眼底病杂志

Objective:To identify the causative genes of the posterior microphthalmia-retinal pigment degeneration family.Methods:A retrospective clinical study. One child (proband) and 3 family members of a family with posterior microphthalmia-retinitis pigmentosa diagnosed by clinical and genetic examination at Henan Provincial People's Hospital in July 2019 were included in the study. Medical history and family history, and draw pedigree of the patients was collected. Visual acuity, visual field, fundus color photography, optical coherence tomography and electroretinogram (ERG) were examined. The peripheral venous blood of the proband, his parents and sister, and extract the whole genome DNA was collected. Whole-exome sequencing was used to detect genetic variations, the suspected pathogenic variations were verified by Sanger sequencing, and the pathogenicity was determined by bioinformatics analysis.Results:The parents discovered the proband was poor vision at the age of 10 months. At the age of 3, the best corrected visual acuity of the right eye and the left eye were 0.3 and 0.4, respectively. No abnormality was found in anterior segment. Extremely high hyperopia in both eyes. The axial length was 14.47 mm and 15.78 mm, respectively. The optic disc of both eyes was relatively small and flushed, retinal folds can be observed in macular area, and no obvious pigment deposition was found. ERG examination showed that the rod system response and the maximal combined response of both eyes decreased slightly to moderately, and the single-flash cone response and the 30 Hz flicker response decreased moderately to severely. Genetic analysis revealed two novel mutations in the membrane frizzled-related protein ( MFRP) gene in the proband: c.363delC/p.Thr121Thrfs*16, c.1627C>T/p.Gln543Stop,37 in exon 4 and 13, the former was a frameshift mutation, encoding 16 amino acids and then terminated, and the latter was an nonsense mutation, truncated 37 amino acids, both which were predicted to be pathogenic and segregate with disease. The mother and sister carried c.363delC, and the father carried c.1627C>T. Conclusion:MFRP gene c.363delC/p.Thr121Thrfs*16, c.1627C >T/p.Gln543Stop, 37 compound heterozygous mutation may be the pathogenic gene of this family.

Genetic screening of the congenital aniridia and genotype-phenotype analysis / 中华实验眼科杂志

Objective@#To explore the genotype-phenotype correlation among 3 pedigrees affected with congenital aniridia.@*Methods@#Clinical data and genomic DNA were collected and genetic variations were screened by whole-exome sequencing, with an emphasis on PAX6-related genes.Suspected variations were verified by Sanger sequencing and quantitative polymerase chain reaction (PCR). Written informed consent was obtained from the parents of each propositus prior to entering study cohort.This study protocol was approved by Ethic Committee of Henan Eye Hospital (No.HNEECKY-2017(6)).@*Results@#Genetic analysis identified that a nonsense c. 949 C>T variation and an c. 141+ 1 G>T splicing variation of the PAX6 gene in two of the probands, while the remainder has carried a duplication in 11 p13 (chr11: 31531331-31827959) encompassing the PAX6 and ELP4 genes.Phenotype analysis showed that the probands carrying the nonsense and splicing variations had classical features including complete aniridia, macular hypoplasia, microcornea and nystagmus; the proband carrying the 11p13 duplication had microphthalmos, microcornea, macular dysplasia, iris dysgenesis, and nystagmus.@*Conclusions@#The 11p13 duplication involving the PAX6 gene may have caused over-expression of PAX6 gene, resulting in severe eye abnormalities including microphthalmos and microcornea, macular dysplasia and nystagmus.The relatively mild iris dysgenesis has distinguishing it from classical aniridia due to PAX6 haploinsufficiency.

Mutation analysis of the autosomal dominant Weill-Marchesani syndrome and genotype-phenotype review / 中华实验眼科杂志

Objective To screen the disease-causing genes in an autosomal dominant (AD)Weill-Marchesani syndrome (WMS) family from Henan province in China,and to analyze the relationship between genotypes and phenotypes of the AD WMS.Methods A family with suspected WMS was collected and studied in Henan Eye Hospital from September 2016 to July 2017.Clinical data and genomic DNA of the families were analyzed and genetic variations were screened by whole-exome sequencing (WES) The candidate genes related to ectopia lentis (FBN1,ADAMTSL2,ADAMTSL4,TGFBR2,CBS,ADAMTS10,ADAMTS17) were analyzed,and multiplex ligation dependent probe amplification (MLPA) was applied.Novel variants were further evaluated by sequencing 96 normal individuals.The previous reports with similar genetic characteristics were reviewed and the mutation types and clinical features were summarized.Written informed consent was obtained from the participants or their guardians before the collection of their venous blood and clinical data.Ethical approval was obtained from the Institutional Review Board of Henan Eye Institute.Results The suspicious mutation of the c.5260G＞A was detected in exon 42 of the FBN1 by WES in this family,which was predicted to be pathogenic and cosegregated with the disease;the clinical futures of the patients in the family included proportionate short stature,brachydactyly,joint stiffness,and the ocular problems included microspherophakia,moderate myopia,secondary glaucoma.Four mutations of FBN1 that related to WMS were reported in previous literature,and three of them were located in 41-42 exons and the others were the deletion of exons 9-11.All patients had typical clinical features of microspherophakia,short stature,brachydactyly,joint stiffness.In addition,thick skin was common,heart defects were occasional,protuberant abdomen and umbilical hernia were rarely reported.Conclusions The affected members in this family are in according with the clinical and genetic diagnosis of WMS.A novel mutation (c.5260G＞A) in FBN1 is discovered,which increases the spectrum of WMS mutation.The 41-42 exons of the FBN1 are hotspot of mutation in WMS.

Pathogenic gene screening and phenotypic analysis of six albinism families / 中华眼底病杂志

Objective To analyze the pathogenic gene types and phenotypic characteristics of 6 albinism families.Methods A retrospective series of case studies.Six probands of albinism and 20 family members were recruited for this study,5 probands with clinical manifestations of oculocutaneous albinism (OCA) and 1 proband of ocular albinism (OA).Genomic DNA was extracted from peripheral venous blood which was collected from 6 probands and 20 family members.Genetic variations were screened by whole-exome sequencing or Sanger sequencing and then analyzed the relationship between genotypes and phenotypes.Results Genetic sequencing identified 6 potential pathogenic variants in 4 probands,including 2 compound heterozygous mutations in the 2 genes [TYR (c.1037-7T＞A,c.925_c.926insC),OCA2 (c.2359G＞A,c.587T＞C)] associated with OCA1 and OCA2,and 2 hemizygous mutations in the GPR143[GPR143 (c.11C ＞ G),GPR 143 (c.333 G ＞ A)] as sociated with OA 1,respectively.In which,5 were novel mutations and confirmed by Sanger sequencing.One case was accorded with OCA in clinical phenotype,but genetic diagnosis was OA1,the others were agreement between clinical diagnosis and genetic diagnosis.Conclusion There are 4 families with mutations in 6 families,representative of 3 type of albinism (OCA1,OCA2,OA1).

The associations between human papilloma viruse persistent infection and Stathmin-1 expression and the clinical significance in cervical intraepithelial neoplasia / 中国医师进修杂志

Objective To explore the relationship between Stathmin-1 and human papilloma viruse (HPV) persistent infection after conization of uterine cervix, and to show the clinical significance to recurrent of cervical intraepithelial neoplasia (CIN). Methods One hundred and six patients who were treated with conization of uterine cervix for CIN 2-3 grades were enrolled. Thirty-six recurrent patients were enrolled in recurrence group, and the others were enrolled in control group. The expression of Stathmin-1 in primary CIN tissues in two groups was detected by immunohistochemistry. The HPV infection was detected by HPV-DNA test. The relationship of HPV persistent infection and recurrence was analyzed. Results The positive expression rate of HPV persistent infection and HPV persistent infection rate in recurrence group were 88.89%(32/36), 83.33%(30/36), in control group were 34.29%(24/70) and 22.86%(16/70), and there were significant difference (P 0.05). Conclusions Stathmin-1 positive expression is related to HPV persistent infection. The two factors can affect the prognosis of high-grade CIN, and can provide new cues and theory basis for the prevention of recurrence.

The efficacy and safety of irinotecan and cisplatin as neoadjuvant chemotherapy for cervical cancer / 中国医师杂志

Objective To explore the efficacy and safety of irinotecan as neoadjuvant chemotherapy (INAC) plus radical surgery (RS) for cervical cancer.Methods According to International Federation of Gynecology and Obstetrics (FIGO),81 cases were divided into Ⅱ B,ⅡA,and Ⅰ B2 groups.According to the tests of UGT1A1 gene polymorphisms,we adjusted the injection dose of irinotecan.The parameters were analyzed,including the efficacy,operation time and bleeding volume,postoperative pathology,survival time,and adverse reactions.The articles on irinotecan or paclitaxel combined with cisplatin for neoadjuvant chemotherapy between 2005 and 2015 were collected,and compared.Results The effective rate of chemotherapy was 81.5％ (Ⅰ B2 group:85.7％;Ⅱ A group:83.3％;and ⅡB group:72.2％),operation time was (5.3 ± 1.1) h,and blood loss was (781 ± 361.7) ml.After chemotherapy,37 cases were delayed diarrhea,70 cases were nausea,48 cases were vomiting,and 40 cases were bone marrow suppression.The infiltration rate,operation time,and blood loss on Ⅱ B group was significantly higher than that on Ⅱ A and Ⅰ B2 groups(P ＜ 0.05),and there was no significant difference in the chemotherapy efficiency,invasion depth,lymphatic metastasis,survival time and adverse reactions(P ＞0.05).Compared to three articles,the total effective rate in this study was higher than that in previous studies,also in Ⅱ A and Ⅱ B group.Conclusions Irinotecan chemotherapy regimens combined with cisplatin is effective and well tolerated.It is worthy of popularization and application.Detection of UGT1A1 gene polymorphism has guiding significance for chemotherapy regimen on irinotecan combined with cisplatin.

Efficacy of Minocycline Against Operculitis of Wisdom Tooth:A Clinical and Experimental Study / 中华医院感染学杂志

0.05).There were significant differences between groups A and C(P

The Effects of Hysterectomy and Uterine Arterial Embolization on the Function of Ovary / 实用放射学杂志

Objective To investigate the effect of hysterectomy and uterine arterial embolization on the function of ovary.Methods The serum concentrations of estrin(E2), progestogen(P),fouicule-stimulating hormone(FSH),luteotropic hormone(LH) and prolaction(PRL) were measured in 18 patients undergone hysterectomy (group Ⅰ),15 patients undergone uterine arterial emboliation(group Ⅱ) and 30normal women (group Ⅲ or control group).These five hormones were compared in each group.Results The serum concentrations of E2 and P in the group Ⅰ were lower than that in group Ⅲ, there was significant difference between them.The serum concentrations of E2 and P in group Ⅱ and group Ⅲ was no significant difference.Conclusion Hysterectomy has significant effects on the function of ovary,while uterine arterial embolization has not.