Paired Box Gene Family: The Taxonomic Structure Distribution and Function / 中国生物化学与分子生物学报

Paired box transcription factors (paired box, PAX) and their homologues found in a large number of vertebrates and invertebrates play a key role in many stages of embryonic development. The gene family gets its name because of its conserved paired domain, in addition to its octapeptide and homologous domain. According to the composition of the domain and sequence homology, the gene family is mainly divided into four subfamilies: PAX1 / 9 (PAX1, PAX9), PAX2 / 5 / 8 (PAX2, PAX5, PAX8), PAX3 / 7 (PAX3, PAX7), PAX4 / 6 (PAX4, PAX6). Each subfamily has different characteristic structures, such as PD-OP of PAX1 / 9 subfamily, PD-OP-PTHD of PAX2 / 5 / 8 subfamily, PD-OP-PTHD of PAX3 / 7 subfamily and PD and PTHD of PAX4 / 6 subfamily. Among them, the three members of the PAX family, PAX2 PAX4 and PAX6, play an important role in multiple stages of pancreatic development and differentiation, and also play a key role in regulating the synthesis and secretion of islet hormone. Understanding the original and differentiated roles of these transcription factors in pancreas will help finding potential treatment for diabetes. Furthermore, PAX1 / 9 families may serve as potential biomarkers for evaluation of tumor development and progression, such as the methylation levels of PAX1 and expression of PAX9 in tumor. PAX3 / 7 was transcription factors involved in the development of skeletal muscle. This paper reviewed the special and temporal expression of PAX genes in a wide variety of tumor and the function and structural abnormalities PAX gene were summarized in this paper.

A novel PAX6 mutation in a Chinese family with congenital aniridia / 中华实验眼科杂志

Background Aniridia is a rare congenital hereditary eye disease.Studies determined that PAX6 gene mutation is closely associated with congenital aniridia,but the mutation locus are varied.Objective This study was to identify virulence mutation locus of PAX6 gene of a Chinese family pedigree with autosomal dominant aniridia.Methods A Chinese family affected with autosomal dominant aniridia was collected and examined in Affiliated First Hospital of Zhengzhou University in August 2014.Periphery blood of 10 ml was collected from all the families and 100 unrelated health controls.The genomic DNA was extracted by standardized phenol-chloroform method,and all exons and splicing junctions of PAX6 were amplified by PCR.Real-time fluorescence quantitative PCR was performed to examine the relative expression of PAX6 mRNA in patients and normal phenotype families and heahh controls.This study protocol was approved by Ethic Committee of Affiliated First Hospital of Zhengzhou University and complied with Helsinki Declaration.Written informed consent was obtained from subjects or custodian before any medical examination.Results This Chinese family inclued 3 generations and 9 members,with a classic autosomal dominant inheritance mode.Five patients were found,showing the absence of iris and cataract in 3 adult patients and only absence of the iris in 2 children,and other 4 members showed the normal phenotype.A novel heterozygous PAX6 deletion mutation c.796 del G (p.A266 fs) (GenBank ID:KP255960) in exon 10 was exclusively found in all affected individuals but not in any of the unaffected families or unrelated health controls.PAX6 mRNA level in lymphocytes was about 50％ lower in aniridia patients than in unaffected family members,indicating that this mutation caused nonsense-mediated mRNA decay.Conclusions A novel deletion mutation in PAX6 gene results in an abnormal PAX6 COOH-terminal extension in the Chinese aniridia family.This finding expands the mutation spectrum of PAX6 gene.

Síndrome de Waardenburg tipo I: relato de caso / Waardenburg syndrome type I: case report

A síndrome de Waardenburg tipo I é uma desordem auditivo-pigmentária que inclui, entre outros, perda auditiva neurossensorial congênita não progressiva, telecanto, distúrbios pigmentares de íris, cabelo e pele. Indivíduos afetados podem ter maior risco de: defeitos no tubo neural, fendas labial e palatina, anormalidades nos membros e doença de Hirschsprung. O diagnóstico é clínico, sendo necessários dois critérios maiores ou um maior e dois menores. PAX3 é o único gene conhecido associado à síndrome, sendo, entretanto, mais usado no aconselhamento genético. Quanto ao diagnóstico diferencial, podemos citar: outras causas de perda auditiva neurossensorial congênita não progressiva, outros tipo de síndrome de Waardenburg, piebaldismo, albinismo, vitiligo e síndrome de Teitz. Neste trabalho, apresenta-se um paciente masculino de 11 anos com diagnóstico de síndrome de Waardenburg tipo I. Ressalta-se a importância do oftalmologista no auxílio do diagnóstico deste raro quadro sistêmico, uma vez que inclui algumas alterações oftalmológicas. O diagnóstico precoce da síndrome permite estimulação adequada para a perda auditiva, assim como medidas preventivas em caso de gestantes afetadas no aconselhamento genético.

Waardenburg syndrome (WS) type I is a non-progressive auditory-pigmentary disorder comprising congenital sensorineural hearing loss and pigmentary disturbances of the iris, hair, and skin, along with dystopia canthorum (lateral displacement of the inner canthi). Affected individuals may have higher risk of: neural tube defects, cleft lip and palate, limb abnormalities, and Hirschsprung disease. The diagnosis is clinical and should be considered if the individual has two major or one major plus two minor criteria. PAX3 is the only known gene associated to the syndrome. Nevertheless, its use is mostly for genetic counseling. Regarding different diagnosis, we may list: other causes of non-progressive auditory-pigmentary disorder comprising congenital sensorineural hearing loss, other types of Waardenburg syndrome, piebaldism, albinism, vitiligo and Teitz syndrome. This paper presents a case of an eleven year old boy with deafness and ophthalmologic alterations, based on his files and exams. It reinforced the importance of the ophthalmologist contributing for the diagnosis of this rare systemic disease, as it includes some ophthalmologic alterations. We remind that the early diagnosis allows adequate stimulation for the hearing loss, as well as preventive measures in case of pregnant women affected by genetic counseling.

Origin of ovarian epithelial inclusions and its relationship with the development of low-grade serous carcinoma / 中华妇产科杂志

Objective To investigate the possible origin of ovarian epithelial inclusions and its relationship with the low-grade ovarian serous carcinoma.Methods By comparatively evaluating the morphologic (secretory and ciliated cell distribution ) and immunophenotypic [using paired box gene 8 (PAX8),tubulin,calretinin,and Ki-67 as first antibodies] attributes of ovarian epithelial inclusions,the normal tubal epithelium,and the ovarian tumors,all adnexal tissues from a total of 198 patients were studied,including 116 adnexae removed for non-neoplastic indications,53 serous cystadenomas,44 serous borderline tumors,and 41 low-grade serous carcinomas,which were collected from Qilu Hospital of Shandong University and University of Arizona in USA.Immunohistochemical single staining was used to detect the expressions of PAX8,tubulin,calretinin,and Ki-67 in the two groups,while immunohistochemical double staining of PAX8/calretinin was used to figure out the immunophenotype of various ovarian epithelial inclusions in a more intuitive way.Results With immunohistochemical single staining of PAX8 and calretinin,the vast majority (90％,54/60) of ovarian surface epithelia displayed a mesothelial phenotype [calretinin(+),PAX8 (-)],whereas 10％ (6/60)of the cases displayed foci with tubal phenotype [calretinin(-),PAX8 (+)].In contrast,most (79％,728/921 ) of the ovarian epithelial inclusions displayed a tubal phenotype,though 21％ (193/921) of the ovarian epithelial inclusions showed a mesothelial phenotype.It was further proved by immunohistochemical double staining of PAX8/ calretinin.Secretory and ciliated cells were found in the ovarian epithelial inclusions with tubal phenotype.There was a progressive increase in the secretory/ciliated cells ratio and proliferative index,from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma,according to the expression of tubulin and Ki-67.Conclusions The findings make a strong argument that the ovarian epithelial inclusions displaying a tubal phenotype with PAX8 (+),calretinin (-) is likely derived from fallopian tube rather than through Mullerian metaplasia from ovarian surface epithelium.The increasing trend of secretory/ciliated cells ratio and proliferative index from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma indicates that the latter is a clonal expansion of secretory cells.Genetic and molecular studies are needed to further confirm these findings.