Spectrum of congenital and inherited ocular disorders seen in a genetic clinic: Experience of a developing ocular genetic service

Purpose: Hereditary causes are an important etiological category of childhood blindness. This study reports the real?world experience of a developing ocular genetic service. Methods: The study was carried out from Jan 2020 to Dec 2021 jointly by the Pediatric Genetic Clinic and the Department of Ophthalmology of a tertiary care hospital in North?West India. Children presenting to the genetic clinic with congenital or late?onset ocular disorder(s) and any individual (irrespective of age) suffering from an ophthalmic disorder and referred by an ophthalmologist for genetic counseling for himself/herself and/or his/her family member(s) were included. Genetic testing (exome sequencing/panel?based sequencing/chromosomal microarray) was outsourced to third?party laboratories with the cost of the test being borne by the patient. Results: Exactly 8.6% of the registered patients in the genetic clinic had ocular disorders. Maximum number of patients belonged to the category of anterior segment dysgenesis, followed by microphthalmia anophthalmia coloboma spectrum, lens disorders, and inherited retinal disorders in decreasing numbers. The ratio of syndromic ocular to isolated ocular disorders seen was 1.8:1. Genetic testing was accepted by 55.5% of families. The genetic testing was clinically useful for ~35% of the tested cohort, with the opportunity for prenatal diagnosis being the most useful application of genetic testing. Conclusion: Syndromic ocular disorders are seen at a higher frequency compared to isolated ocular disorders in a genetic clinic. Opportunity for prenatal diagnosis is the most useful application of genetic testing in ocular disorders.

Research progress of Sox2 gene in eye diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Sox2 gene is a member of sex determination region of Y chromosome(SRY)related gene family, and it is one of the key transcription factors to maintain the pluripotency and self-renewal characteristics of embryonic stem cells. Sox2 participates in a variety of biological processes, such as regulating cell proliferation and apoptosis, and participating in the formation and development of tumors. However, the review literature on the role of Sox2 gene in eye diseases has not been reported. This article reviews the expression level of Sox2 gene, related signal pathways and clinical application potential, so that readers can understand more comprehensive the role of Sox2 gene in eye diseases, and to carry out more in-depth research.

MicroRNA-100-5p Regulates Melanogenesis in Alpaca Melanocytes by Targeting FGF21 / 中国生物化学与分子生物学报

Although many microRNAs (miRNAs) are known to function as regulators of coat color and melanogenesis, the underlying molecular mechanisms of miR-100-5p governing melanogenesis were not completely known.The goal of this study was to determine the effect of miR-l()()-5p on melanogenesis in alpaca melanocytes.Fibroblast growth factor 21 (FGF21) is a predicted target gene of miR-100-5p and the luciferase reporter assay demonstrated that miR-100-5p regulates FGF21 by binding to its 3' untranslated region (3'UTR).In this study, alpaca melanocytes were transfected with miR-100-5p, inhibitor and negative control plasmid.Results showed that miR-100-5p overexpression significantly decreased mRNA and protein expression of FGF2\.Meanwhile, the ERK signal pathway was inhibited, with subsequent up-regulation of microphthalmia-associated transcription factor (MITF) , tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2), which increased melanin production.The results suggest that miR-100-5p may regulate melanogenesis by targeting FGF21 via extracellular regulated MAP kinase (ERK) signaling pathway.

DKK3 Regulates Melanogenesis in Melanocytes of Alpaca / 中国生物化学与分子生物学报

Dickkopf-3 (DKK3) , as a critical inhibitor of the Wnt/p-catenin signaling pathway, may he involved in melanogenesis.In the current study, we investigated the effects of DKK3 on melanogenesis in melanocytes of alpaca.Overexpression of DKK3 in alpaca melanocytes, the expression of Wntl, Lefl , Myc and the major target genes termed microphthalmia-associated transcription factor (M1TF) and its downstream genes, including tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1) and tyrosinase- related protein 2 (TYRP2) were significantly decreased at both mRNA and protein levels (P<0.05); total alkali melanin, pheomelanin and eumelanin were decreased by 80.30%, 72.17% and 64.60% (P <0.05), respectively.In contrast, in the melanocytes transfected with siRNA-DKK3 (a small interference RNA targeting DKK3) , the expression of Wntl, Lefl, Myc, MITF, TYR, TYRPl and TYRP2 were significantly increased at both mRNA and protein levels (P<0.05) ; total alkali melanin, pheomelanin and eumelanin were significantly increased by 1.65 folds, 1.25 folds and 1.21 folds (P< 0.05) , respectively.These results indicate that DKK3 regulates melanogenesis in alpaca melanocytes via the Wnt/p-catenin signaling pathway and down-regulates MITF.

Prenatal diagnosis of bilateral congenital microphthalmia in two fetuses from the same parents

Congenital microphthalmia (CM) is a rare anomaly of the fetal orbit, results from developmental defects of the primary optic vesicle, and is characterized by a reduced eyeball volume and axial diameter. Fetal CM cases have rarely been reported. Herein, we present a case of two fetuses with bilateral CM from the same parents, diagnosed using ultrasonography (US) and magnetic resonance imaging (MRI). We found that the antepartum US and MRI measurements were smaller than the postpartum ones. Genetic testing of the parents and fetuses revealed that GL12 gene mutation may be associated with CM.

Prenatal ultrasound diagnosis of fetal microphthalmia / 中华超声影像学杂志

Objective To analyze the ultrasonic features ,associated malformations and combined genetic abnormalities of microphthalmia . Methods The characteristics of 15 cases of fetal microphthalmia were retrospectively analyzed . And the proportion of fetal microphthalmia associated malformations were further assessed according to the different organ system . Results All the orbital diameters of affected eyes of the 15 cases were less than the 5th centile of normal fetal orbital diameter corresponding to gestational age . In which ,26 .67% ( 4/15 ) fetuses had additional ocular defects ,and 66 .67% ( 10/15 ) were diagnosis with extrocular defects ,including 20 .00% ( 3/15) with central nervous system defects ,13 .33% ( 2/15) with orofacial defects ,26 .67% ( 4/15) with cardiac defect ,13 .33% ( 2/15) with limb defect ,33 .33% ( 2/15) with urogenital defect and 40 .00% ( 6/15 ) with abnormal ultrasonographic soft markers . And the proportion of fetal microphthalmia associated extrocular defects showed no significant difference ( P ＝ 0 .502 ) . Conclusions Fetal microphthalmia is frequently associated with random and sporadic occurrence of extrocular defects

Prenatal ultrasound diagnosis of fetal microphthalmia / 中华超声影像学杂志

Objective@#To analyze the ultrasonic features, associated malformations and combined genetic abnormalities of microphthalmia .@*Methods@#The characteristics of 15 cases of fetal microphthalmia were retrospectively analyzed. And the proportion of fetal microphthalmia associated malformations were further assessed according to the different organ system.@*Results@#All the orbital diameters of affected eyes of the 15 cases were less than the 5th centile of normal fetal orbital diameter corresponding to gestational age. In which, 26.67%(4/15) fetuses had additional ocular defects, and 66.67%(10/15) were diagnosis with extrocular defects, including 20.00%(3/15) with central nervous system defects, 13.33%(2/15) with orofacial defects, 26.67% (4/15) with cardiac defect, 13.33%(2/15) with limb defect, 33.33% (2/15) with urogenital defect and 40.00%(6/15) with abnormal ultrasonographic soft markers. And the proportion of fetal microphthalmia associated extrocular defects showed no significant difference(P=0.502).@*Conclusions@#Fetal microphthalmia is frequently associated with random and sporadic occurrence of extrocular defects

Research progress in melanogenesis signaling pathway / 生物工程学报

Melanogenesis is a biosynthetic pathway to produce melanin pigment in melanocyte, involving a series of intricate enzymatic and chemical catalyzed reactions. Melanogenesis involves five signaling pathways that converge on microphthalmia-associated transcription factor. In addition, many cytokines, involved in the regulation of melanogenesis, play an important role in the development, proliferation, differentiation and migration of melanocytes. Polyoxometalate can be used as a potential inhibitor of melanin production. Hence, this paper reviews the signaling pathways of melanogenesis and their regulatory mechanism, to apply polyoxometalates in the melanin production pathway, and briefly introduces the regulatory factors of related pathways.

Effect of latanoprost on cell proliferation of and melanogenesis in human epidermal melanocytes and its mechanism / 中华皮肤科杂志

Objective To evaluate the effect of latanoprost on cell proliferation of and melanogenesis in human epidermal melanocytes,and to explore its mechanism.Methods Latanoprost was added into the 254 medium to prepare latanoprost solutions at different concentrations of 10-5,10-6 and 10-7 mol/L.In vitro cultured human epidermal melanocytes were divided into 4 groups to be cultured with media containing no latanoprost (control group) or 10-5,10-6 and 10-7 mol/L latanoprost for 48 hours.Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative activity of melanocytes,dopa oxidation assay to estimate the activity of tyrosinase.Sodium hydroxide (NaOH)-lysis method was used to determine the content of melanin,and Masson-Fontana staining to observe the number and distribution of melanin granules.Westernblot analysis and real-time fluorescence-based quantitative PCR were performed to determine the protein and mRNA expression of melanogenesis-related genes including microphthalmia-associated transcription factor (MITF),tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1).Comparison among the 4 groups and multiple comparisons were done by using one-way analysis of variance and least significant difference (LSD)-t test.Results Compared with the control group,the 10-6-,10-5-mol/L latanoprost groups showed significantly increased proliferative activity of melanocytes (1.064 ± 0.172 and 1.078 ± 0.080 vs.0.784 ± 0.015;t =3.289,3.454 respectively,both P ＜ 0.05),increased activity of tyrosinase (0.510 ± 0.017 and 0.454 ± 0.009 vs.0.355 ± 0.041;t =6.139,3.939 respectively,P ＜ 0.01 or 0.05),and increased content of melanin (t =7.232,5.967,both P ＜ 0.01).However,there were no significant differences in the proliferative activity of melanocytes,activity of tyrosinase or content of melanin between the 10-7-mol/L latanoprost group and control group (all P ＞ 0.05).Masson-Fontana staining showed more and darker melanin granules on melanocyte dendrites in the 10-5-,10-6-,10-7-mol/L latanoprost groups than in the control group,and the color of melanin granules changed from light brown to black brown along with the increase in the concentration of latanoprost.The mRNA expression of MITF increased along with the increase in the concentration of latanoprost (P ＜ 0.01),and the protein expression of MITF wassignificantly higher in the 10-6,10-5-mol/L latanoprost groups than in the control group and 10-7-mol/L latanoprost group (all P ＜ 0.01).The 10-6-mol/L latanoprost group showed significantly increased mRNA and protein expression of TYR and TYRP1 compared with the control group,10-7-,10-5-mol/L latanoprost groups (all P ＜ 0.01).Conclusion Latanoprost can increase the proliferation of human epidermal melanocytes,and promote tyrosinase activity and melanogenesis likely by enhancing the mRNA and protein expression of MITF,TYR,TYRP1.

Inhibitory effect of miR-34a on biological behavior of uveal melanoma cells and its mechanism / 中华实验眼科杂志

Objective To study the effect of microRNA-34a(miR-34a) on the biological behavior of uveal melanoma cells and its mechanism.Methods Uveal melanoma M23 cells were used as research objects,miR-34a mimics and mimics negative control were transfected into the cells respectively as miR-34a transfection group and the negative control group,and the non-transfected cells served as the normal control group.The overexpression effect was validated by real-time PCR.MTT assay was used to detect cell proliferation.Cell invasion and migration were detected by Transwell test.Target gene prediction library predicted target genes of miR-34a,and the target gene was identified by luciferase activity report.Real-time PCR and Western blot were used to detect the mRNA and protein expression of target genes.MiR-34a mimics and microphthalmia-associtated transcription factor (MITF) overexpression vectors were cotransfected into M23 cells.Cell proliferation,invasion and migration abilities were detected by MTT assay and Transwell test,respectively.The mRNA and protein expressions of MITF were detected by real-time PCR and Western blot.Results The expression of miR-34a in M23 cells transfected with miR-34a mimics increased.The cell proliferation (A570),number of invasive cells and migrating cells were significantly different among the miR-34a transfection group,negative control group and normal control group (F =18.000,P =0.003;F =20.345,P =0.002;F=15.717,P=0.004).The proliferation,invasion and migration ability of M23 cells in the miR-34a transfection group were significantly decreased compared with the negative control group and normal control group (all at P＜0.05).Target gene prediction library and luciferase activity report showed that MITF was the target gene of miR-34a.The relative expression levels of MITF mRNA and protein were 0.45 ±0.06 and 0.36± 0.04 in the miR-34a transfection group,0.99± 0.11 and 0.62 ± 0.05 in the negative control group,1.00 ± 0.07 and 0.63 ± 0.08 in the normal control group,respectively,and compared with the negative control group and normal control group,the expression of MITF in miR-34a transfection group were significantly decreased (all at P＜0.05).Cell proliferation (A570),the number of invasived cells and the number of migrated cells were 0.35±0.02,29.48±3.20 and 41.87±5.82 in the miR-34a + MITF group,0.26 ± 0.03,18.53 ± 1.47 and 27.64 ± 2.45 in the miR-34a + Vector group,respectively,the proliferation,invasion and migration ability of the cell.s in the miR-34a+MITF group was significantly higher than that in the miR-34a+Vector group (all at P＜0.05).Conclusions miR-34a can inhibit the malignant phenotype of uveal melanoma cells by inhibiting the expression of the target gene MITF.

Importancia de la neuroimagen en la anoftalmia/microftalmia congénita neonatal: a propósito de un caso / Importance of neuroimaging in neonatal congenital anophthalmia/microphthalmia: a case report

Introducción: La Anoftalmia/Microftalmia es una malformación ocular congénita que se caracteriza por la reducción variable del volumen del globo ocular, la misma requiere de estudios imagenológicos para un diagnóstico más preciso. Objetivo: Demostrar la importancia de la neuroimagen en el diagnóstico y orientación de la microftalmia/anoftalmia neonatal congénita bilateral. Presentación del caso: Se hace referencia a un recién nacido con diagnóstico clínico de anoftalmia/microftalmia de manera inicial que después de realizar estudios de neuroimagen se constataron otras malformaciones del sistema nervioso central que permitieron orientar el diagnóstico hacia un síndrome genético definido. Durante el examen físico inicial se constató hipertelorismo, orejas de implantación baja, fisura palatina, ano anterior y ausencia de los globos oculares en ambos lados. La Resonancia magnética nuclear mostró esbozos de cristalinos rudimentarios, ubicados en zona atípica y esbozo de nervio óptico incompleto del lado derecho. No se observaron globos oculares. Observándose además múltiples imágenes de aspecto quístico bilaterales en las áreas orbitarias que desplazan los cristalinos rudimentarios por conflicto de espacio. Este paciente requirió estudios de neuroimagen para determinar si se trataba de una anoftalmia/microftalmia y para orientar el diagnóstico de displasia septo-óptica que organizó el pensamiento clínico hacia un posible Síndrome de Morsier. En este caso se realizó diagnóstico diferencial con otras causas asociadas a estas malformaciones oculares. Conclusiones: Los estudios imagenológicos del cerebro de los pacientes con anoftalmia / microftalmia en la etapa neonatal permiten orientar un diagnóstico preciso y precoz que favorece una intervención multidisciplinaria temprana(AU)

Introduction: Anophthalmia/microphthalmia is a congenital eye malformation that is characterized by the variable reduction of the volume of the ocular globe, which requires imaging studies for a more precise diagnosis. Objective: To demonstrate the importance of neuroimaging in the diagnosis and management of neonatal congenital bilateral anophthalmia/microphthalmia. Case Presentation: We describe the case of a newborn with an initial clinical diagnosis of anophthalmia/microphthalmia in which, after carrying out neuroimaging studies, other malformations of the central nervous system were confirmed, allowing to guide the diagnosis towards a defined genetic syndrome. During the initial physical exam, hypertelorism, low set ears, palatine fissure, anterior anus, and absence of the ocular globes in both sides were verified. The magnetic resonance imaging showed signals of rudimentary crystalline located in an atypical area, and signals of incomplete optic nerve of the right side. Ocular globes were not observed. Multiple cyst-like bilateral images were also observed in orbital areas, displacing the rudimentary crystalline lens due to space limitations. Discussion: This patient required neuroimaging studies to determine if she had an anophthalmia/microphthalmia and present a guide for the diagnosis of septo-optic dysplasia that organized the clinical thinking towards a possible Morsier Syndrome. In this case, a differential diagnosis with other causes associated to these ocular malformations was made. Conclusions: The imaging studies of the brain of the patients with anophthalmia/microphthalmia in the neonatal period allows to guide a precise and early diagnosis that favors an early multidisciplinary intervention(AU)

Mechanism for synergistic effect of IRF4 and MITF on tyrosinase promoter / 中南大学学报(医学版)

Objective:To investigate the mechanism for the synergistic effect of interferon regulatory factor 4 (IRF4) and microphthalmia-associated transcription factor (MITF) on tyrosinase (TYR)promoter.Methods:The synergistic transcriptional effect,subcellular localization,and protein-protein interaction for IRF4 and MITF were observed by luciferase assay,immunofluorescence,GST-pull down,and co-immunoprecipitation,respectively.Results:IRF4 and MITF proteins were co-expressed in the cell nucleus.IRF4 augmented the transcriptional function of MITF (but not the mutant MITF) to activate the expression of the TYR promoter,but with no effect on other MITF-specific target promoters.IRF4 alone did not affect TYR promoter significantly.No direct interaction between the two proteins was noted.Conclusion:IRF4 and MITF exert a specifically synergistic effect on activation of TYR promoter through IRF4-mediated upregulation of transcriptional function of MITF.This synergistic effect is mainly regulated by MITF;DNA might be involved in the interaction between the two proteins.

Mechanism of microphthalmia family of transcription factors in tumorigenesis / 国际肿瘤学杂志

Microphthalmia family of transcription factors (MiT/TFE) is very important for the regulation of cancer cell proliferation and energy metabolism.The MiT/TFE promotes the genesis and development of tumors by up-regulating the expression of lysosomal genes as well as acting on the oxidative metabolism and the oxidative stress response.MiT/TFE can also regulate lysosomal signaling including the mTORC1 and Wnt/3-catenin pathways.The relationship between MiT/TFE and folliculin (FLCN) is associated with the tumorigenesis.

Sageretia thea fruit extracts rich in methyl linoleate and methyl linolenate downregulate melanogenesis via the Akt/GSK3β signaling pathway

BACKGROUND/OBJECTIVES: Sageretia thea is traditionally used as a medicinal herb to treat various diseases, including skin disorders, in China and Korea. This study evaluated the inhibitory effect of Sageretia thea fruit on melanogenesis and its underlying mechanisms in B16F10 mouse melanoma cells. The active chemical compounds in anti-melanogenesis were determined in Sageretia thea. MATERIALS/METHODS: Solvent fractions from the crude extract were investigated for anti-melanogenic activities. These activities and the mechanism of anti-melanogenesis in B16F10 cells were examined by determining melanin content and tyrosinase activity, and by performing western blotting. RESULTS: The n-hexane fraction of Sageretia thea fruit (HFSF) exhibited significant anti-melanogenic activity among the various solvent fractions without reducing viability of B16F10 cells. The HFSF suppressed the expression of tyrosinase and tyrosinase-related protein 1 (TRP1). The reduction of microphthalmia-associated transcription factor (MITF) expression by the HFSF was mediated by the Akt/glycogen synthase kinase 3 beta (GSK3β) signaling pathway, which promotes the reduction of β-catenin. Treatment with the GSK3β inhibitor 6-bromoindirubin-3'-oxime (BIO) restored HFSF-induced inhibition of MITF expression. The HFSF bioactive constituents responsible for anti-melanogenic activity were identified by bioassay-guided fractionation and gas chromatography-mass spectrometry analysis as methyl linoleate and methyl linolenate. CONCLUSIONS: These results indicate that HFSF and its constituents, methyl linoleate and methyl linolenate, could be used as whitening agents in cosmetics and have potential for treating hyperpigmentation disorders in the clinic.

Role of microphthalmia-associated transcription factor in melanoma metastasis / 国际肿瘤学杂志

In recent years, the function of microphthalmia-associated transcription factor (MITF) is a hot field in melanoma.The abnormal expression of MITF is closely related to the occurrence and metastasis of melanoma.In addition, the down expression of MITF promotes its invasion.Studying the regulation of MITF and its related molecules and signaling pathways will let us further understand the molecule mechanism of malignant melanoma metastasis and provide help to exploit novel molecular targeted drug.

Oculodentodigital dysplasia.

Oculodentodigital dysplasia is a rare, autosomal dominant disorder with high penetrance and variable expressivity, caused by mutations in the connexin 43 or gap junction protein alpha‑1 gene. It has been diagnosed in fewer than 300 people worldwide with an incidence of around 1 in 10 million. It affects many parts of the body, particularly eyes (oculo), teeth (dento), and fingers and/or toes (digital). The common clinical features include facial dysmorphism with thin nose, microphthalmia, syndactyly, tooth anomalies such as enamel hypoplasia, anodontia, microdontia, early tooth loss and conductive deafness. Other less common features are abnormalities of the skin and its appendages, such as brittle nails, sparse hair, and neurological abnormalities. To prevent this syndrome from being overlooked, awareness of possible symptoms is necessary. Early recognition can prevent blindness, dental problems and learning disabilities. Described here is the case of a 21‑year‑old male who presented to the ophthalmology outpatient department with a complaint of bilateral progressive loss of vision since childhood.

Promotive effect of puerarin on melanogenesis in melanocytes and its possible mechanisms / 中华皮肤科杂志

Objective To evaluate the effect of puerarin on melanogenesis in melanocytes,and to explore its possible mechanisms.Methods Third-to fifth-passage melanocytes isolated from human foreskin were treated with different concentrations (1,5,10,20,40,80 and 160 μmol/L) of puerarin for 24 hours,with those receiving no treatment as the normal control group.Methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate the proliferative activity of melanocytes,a sodium hydroxide solubilization method was used to measure melanin content,and reverse transcription PCR (RT-PCR) and Western blot analysis were performed to quantify the mRNA and protein expressions of microphthalmia-associated transcription factor (MITF),tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1) respectively.Results There were no significant differences in the proliferative activity of melanocytes between the puerarin (1-40 μmol/L) groups and normal control group (P ＞ 0.05),and 40 μmol/L was chosen as the concentration of puerarin for subsequent experiments.Compared with the normal control group,the 40-μmol/L puerarin group showed increased melanin content as well as mRNA and protein expressions of MITF,TYR and TRP-1 (all P ＜ 0.05).Concretely speaking,the protein expressions of MITF,TYR and TRP-1 in the 40-μmol/L puerarin group were increased by 8.69％,10.28％ and 10.58％ compared with the normal control group respectively (all P ＜ 0.05),and their mRNA expressions were 2.48,1.91 and 1.63 times higher in the 40-μmol/L puerarin group than in the normal control group respectively (all P ＜ 0.05).Conclusion Puerarin can increase the mRNA and protein expressions of MITF,TYR and TRP-1,and promote melanogenesis in melanocytes.

Pigmentation Effect of Electromagnetic Fields at Various Intensities to Melanocytes

Melanogenesis is the biological process that results in the synthesis of skin pigment of melanin and it has various functions in living systems and is synthesized by the melanosome within the melanocytes. A variety of physical treatments are used to promote melanin production in the melanocytes for pigmentation control. The purpose of this study was to evaluate the intensity-dependent effect of extremely low-frequency electromagnetic fields (ELF-EMFs) on melanogenesis by melanocytes in vitro. Melanocytes were exposed to ELF-EMFs at a frequency of 50 Hz and at intensities in the range of 0.5–20 G over 4 days. The results of lactate dehydrogenase assay showed that there were no significant differences between cells exposed to 0.5 G or 2 G groups and the controls. The melanin contents increased 1.2–1.5-fold in cells exposed to ELF-EMFs and tyrosinase activity increased 1.3-fold in cells exposed to ELF-EMFs, relative to the controls. Also, exposure to ELF-EMFs was associated with activation in cyclic-AMP response element binding protein and microphthalmia-associated transcription factor (MITF) was up-regulated. Up-regulation of MITF induces the expression of melanogenesis-related markers, such as tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2. In conclusion, the present study showed that the exposure to ELF-EMFs at low intensities can stimulate melanogenesis in melanocyte, and these results may be used to a therapeutic devices for inducing repigmentation in vitiligo patients.

Síndrome cerebro-óculo-nasal con diagnóstico prenatal / Cerebro-óculo-nasal syndrome with prenatal diagnosis

El síndrome cerebro-óculo-nasal se caracteriza por anomalías del sistema nervioso central, oculares y nasales. La prevalencia de este síndrome es muy baja, y aún no se ha identificado la etiología de esta condición. Se presenta el caso de un paciente con sospecha cínica de este síndrome con diagnóstico prenatal por ecografía 2D y 3D. Se realiza una revisión de la literatura de los casos previamente reportados.

The cerebro-óculo-nasal syndrome is characterized by central nervous system abnormalities, ocular and nasal. The prevalence of this syndrome is very low, and has not yet identified the etiology of this condition. We report the case of a patient with suspected PJS cynical prenatal diagnosis by 2D and 3D ultrasound. A review of the literature of previously reported cases.

Experimental Studies on Regulation of PAX3 on Transcriptional Activities of Target Gene MITF / 听力学及言语疾病杂志

Objective To investigate the impact of pair box 3 (PAX3) gene mutations on transcriptional ac‐tivity of target gene microphthalmia -associated transcription factor (MITF) and the role it plays in the pathogene‐sis of Waardenburg syndrome type I .Methods The 293T cells were transient transfected with wild type (WT ) PAX3 and mutant type (M T ) H80D ,H186fsX5 plasmids .We observed and analysed the regulation effects of WT/MT PAX3 on the transcriptional activities of MITF and the influence of the two mutants on WT PAX3 function u‐sing luciferase activity assays ,detect DNA binding capacity of WT/MT PAX3 to MITF gene promoter using a bioti‐nylated double - stranded oligonucleotide probe containing PAX3 binding motif ATTAAT to precipitate PAX3 , H80D and H186fsX5 respectively .Results H80D mutant was partially functional and was able to transactivate the MITF promoter in part ,but it was dramatically reduced as compared with WT PAX 3(P0 .05) .WT PAX3 and H80D mutant were able to bind specifically to the ATTAAT motif on the MITF promoter ,whereas H186fsX5 PAX3 lost the DNA -binding ability .Conclusion The mutations H80D and H186fsX5 made down-regulation of MITF transcription and decrease syn‐thesis of melanin ,which resulted in haploinsufficiency of PAX3 protein and caused mild phenotypes of WS1 .