Anophthalmia is defined as a complete absence of one eye or both the eyes,while microphthalmia represents the presence of a small eye within the orbit.The estimated birth prevalence for anophthalmia is approximately 3...Anophthalmia is defined as a complete absence of one eye or both the eyes,while microphthalmia represents the presence of a small eye within the orbit.The estimated birth prevalence for anophthalmia is approximately 3 per 100000 live births,and for microphthalmia,it is around 14 per 100000 live births.However,combined evidence suggests that the prevalence of these malformations could be as high as 30 per 100000 individuals.Microphthalmia is reported to occur in 3.2%to 11.2%of blind children.Anophthalmia and microphthalmia(A/M)are part of a phenotypic spectrum alongside ocular coloboma,hypothesized to share a com-mon genetic basis.Both A/M can occur in isolation or as part of a syndrome.Their complex etiology involves chromosomal aberrations,monogenic inheritance pattern,and the contribution of environmental factors such as gestational-acquired infections,maternal vitamin A deficiency(VAD),exposure to X-rays,solvent misuse,and thalidomide exposure.A/M exhibit significant clinical and genetic heterogeneity with over 90 genes identified so far.Familial cases of A/M have a complex genetic basis,including all Mendelian modes of inheritance,i.e.,autosomal dominant,recessive,and X-linked.Most cases arise sporadically due to de novo mutations.Examining gene expression during eye development and the effects of various environmental variables will help us better understand the phenotypic heterogeneity found in A/M,leading to more effective diagnosis and management strategies.The present review focuses on key genetic factors,developmental abnormalities,and environmental modifiers linked with A/M.It also emphasizes at potential research areas including multiomic methods and disease modeling with induced pluripotent stem cell technologies,which aim to create innovative treatment options.展开更多
AIM:To identify the genetic factors underlying anophthalmia and microphthalmia(A/M),and to perform computational analysis to verify the pathophysiological mechanisms of the disease.METHODS:This study investigated a co...AIM:To identify the genetic factors underlying anophthalmia and microphthalmia(A/M),and to perform computational analysis to verify the pathophysiological mechanisms of the disease.METHODS:This study investigated a consanguineous Pakistani family with multiple affected individuals.Clinical evaluations were conducted using A-Scan and ophthalmic B-Scan ultrasonography(B-Scan).To identify the diseasecausing variant,whole exome sequencing(WES)and Sanger sequencing were performed.In silico functional analyses were carried out using AlphaFold(for protein modeling)and ClusPro(for protein docking analysis)tools,and the hydrodynamic properties of the protein were determined via molecular dynamics simulations.RESULTS:Clinical analysis of the five patients revealed severe phenotypes of bilateral anophthalmia.Ocular B-Scan did not detect ocular tissue or intraocular fluid,thus confirming the diagnosis of anophthalmia in all patients.Due to these structural defects,all patients exhibited complete blindness and absence of light perception;additionally,two patients had mild to moderate intellectual disability.Genetic analysis identified a splice site variant[NM_000693.2:c.884-2_885dup;p.(Asp296SerfsTer35)]in the 9^(th)exon of the ALDH1A3 gene.CONCLUSION:The present study expands the genetic spectrum of ALDH1A3 and contributes to establishing the genotype-phenotype correlation for this gene.展开更多
Anophthalmia is a condition of the absence of an eye and the presence of a small eye within the orbit.It is associated with many known syndromes.Clinical findings,as well as imaging modalities and genetic analysis,are...Anophthalmia is a condition of the absence of an eye and the presence of a small eye within the orbit.It is associated with many known syndromes.Clinical findings,as well as imaging modalities and genetic analysis,are important in making the diagnosis.Imaging modalities are crucial scanning methods.Cryptophthalmos,cyclopia,synophthalmia and congenital cystic eye should be considered in differential diagnoses.We report two clinical anophthalmic siblings,emphasizing the importance of neuroradiological and orbital imaging findings in distinguishing true congenital anophthalmia from clinical anophthalmia.展开更多
We describe a female Nigerian infant of otherwise healthy parents with no prior history of congenital anomalies who was born with left-sided cleft lip and palate, left anophthalmia, malformed left auricle, an atrial s...We describe a female Nigerian infant of otherwise healthy parents with no prior history of congenital anomalies who was born with left-sided cleft lip and palate, left anophthalmia, malformed left auricle, an atrial septal defect, and abnormal fusion of the medial ends of her ribs prior to their insertion into the sternum. She presented on account of respiratory difficulty following bouts of feed aspiration. Cautious feeding and the need for respiratory support are important aspects of care in patients with Goldenhar syndrome.展开更多
A smooth and timely fitting of a visually appealing,custom-made eye prosthesis after the loss of an eye is not only essential from a cosmetic point of view but above all facilitates good social and psychological rehab...A smooth and timely fitting of a visually appealing,custom-made eye prosthesis after the loss of an eye is not only essential from a cosmetic point of view but above all facilitates good social and psychological rehabilitation.Cryolite glass prostheses must be replaced at least once a year,PMMA prostheses polished once a year and renewed every five years.In children,especially in growth phases,the fit of the prosthesis should be checked at least every six months and adjusted,if necessary.Ocularists and ophthalmologists should determine an individual cleaning procedure together with the patient,which depends on both the prosthesis material and external factors.Complications such as allergic,giant papillary,viral,and bacterial conjunctivitis or even blepharoconjunctivitis sicca must be detected and treated at an early stage to avoid discomfort and to maintain the ability of prosthesis wear.In the case of inflammation-induced shrinkage of the conjunctival fornices or post-enucleation socket syndrome,surgical interventions are necessary.In summary,an early supply with an eye prosthesis,adequate treatment of complications,and attention to psychological aspects,form the basis for a successful long-term rehabilitation of anophthalmic patients.展开更多
Sox2基因是SRY(sex determination region of Y chromosome)相关基因家族中的一员,是维持胚胎干细胞多能性和自我更新特性的关键转录因子之一。Sox2参与多种生物学过程,如调节细胞增殖和凋亡、参与肿瘤的形成和发展等。但关于Sox2基因...Sox2基因是SRY(sex determination region of Y chromosome)相关基因家族中的一员,是维持胚胎干细胞多能性和自我更新特性的关键转录因子之一。Sox2参与多种生物学过程,如调节细胞增殖和凋亡、参与肿瘤的形成和发展等。但关于Sox2基因在眼部疾病中作用研究的综述较少,为此,本文从Sox2基因的表达水平、相关信号通路及临床应用潜能等方面进行综述,以便于读者对Sox2基因在眼部疾病中的作用有更全面的认识和了解,开展更深入的研究。展开更多
Pesticides are reported to be teratogenic for non-target species.Our studies have unraveled the teratogenicity of 50%Chlorpyrifos&5%Cypermethrin combination(Ci)in developing chick embryos.A sublethal dose of this ...Pesticides are reported to be teratogenic for non-target species.Our studies have unraveled the teratogenicity of 50%Chlorpyrifos&5%Cypermethrin combination(Ci)in developing chick embryos.A sublethal dose of this combination when administered to chick embryos,caused several developmental anomalies,with defects in eye development being frequent.Eye development begins at an early embryonic stage,with Sonic hedgehog(Shh)serving as a crucial signaling molecule.Shh plays a pivotal role in the early development of multiple organs,including the eye,by interacting with Pax6 and other regulatory molecules to guide the proper patterning of the eye.Thus,we hypothesized that Ci administration may lead to alteration in Shh expression which subsequently hampers downstream signaling molecules potentially contributing to congenital eye defects.Morphological,anatomical,histological,transcriptional and protein level analyses at various stages(Days 1,2,4 and 10)were carried out to evaluate the hypothesis.The results revealed a remarkable alteration of key regulators in treated embryos compared to control,providing insights into plausible causative mechanisms underlying Ciinduced congenital eye defects.展开更多
文摘Anophthalmia is defined as a complete absence of one eye or both the eyes,while microphthalmia represents the presence of a small eye within the orbit.The estimated birth prevalence for anophthalmia is approximately 3 per 100000 live births,and for microphthalmia,it is around 14 per 100000 live births.However,combined evidence suggests that the prevalence of these malformations could be as high as 30 per 100000 individuals.Microphthalmia is reported to occur in 3.2%to 11.2%of blind children.Anophthalmia and microphthalmia(A/M)are part of a phenotypic spectrum alongside ocular coloboma,hypothesized to share a com-mon genetic basis.Both A/M can occur in isolation or as part of a syndrome.Their complex etiology involves chromosomal aberrations,monogenic inheritance pattern,and the contribution of environmental factors such as gestational-acquired infections,maternal vitamin A deficiency(VAD),exposure to X-rays,solvent misuse,and thalidomide exposure.A/M exhibit significant clinical and genetic heterogeneity with over 90 genes identified so far.Familial cases of A/M have a complex genetic basis,including all Mendelian modes of inheritance,i.e.,autosomal dominant,recessive,and X-linked.Most cases arise sporadically due to de novo mutations.Examining gene expression during eye development and the effects of various environmental variables will help us better understand the phenotypic heterogeneity found in A/M,leading to more effective diagnosis and management strategies.The present review focuses on key genetic factors,developmental abnormalities,and environmental modifiers linked with A/M.It also emphasizes at potential research areas including multiomic methods and disease modeling with induced pluripotent stem cell technologies,which aim to create innovative treatment options.
基金Supported by Taif University,Taif,Saudi Arabia(TU-DSPP-2024-05).
文摘AIM:To identify the genetic factors underlying anophthalmia and microphthalmia(A/M),and to perform computational analysis to verify the pathophysiological mechanisms of the disease.METHODS:This study investigated a consanguineous Pakistani family with multiple affected individuals.Clinical evaluations were conducted using A-Scan and ophthalmic B-Scan ultrasonography(B-Scan).To identify the diseasecausing variant,whole exome sequencing(WES)and Sanger sequencing were performed.In silico functional analyses were carried out using AlphaFold(for protein modeling)and ClusPro(for protein docking analysis)tools,and the hydrodynamic properties of the protein were determined via molecular dynamics simulations.RESULTS:Clinical analysis of the five patients revealed severe phenotypes of bilateral anophthalmia.Ocular B-Scan did not detect ocular tissue or intraocular fluid,thus confirming the diagnosis of anophthalmia in all patients.Due to these structural defects,all patients exhibited complete blindness and absence of light perception;additionally,two patients had mild to moderate intellectual disability.Genetic analysis identified a splice site variant[NM_000693.2:c.884-2_885dup;p.(Asp296SerfsTer35)]in the 9^(th)exon of the ALDH1A3 gene.CONCLUSION:The present study expands the genetic spectrum of ALDH1A3 and contributes to establishing the genotype-phenotype correlation for this gene.
文摘Anophthalmia is a condition of the absence of an eye and the presence of a small eye within the orbit.It is associated with many known syndromes.Clinical findings,as well as imaging modalities and genetic analysis,are important in making the diagnosis.Imaging modalities are crucial scanning methods.Cryptophthalmos,cyclopia,synophthalmia and congenital cystic eye should be considered in differential diagnoses.We report two clinical anophthalmic siblings,emphasizing the importance of neuroradiological and orbital imaging findings in distinguishing true congenital anophthalmia from clinical anophthalmia.
文摘We describe a female Nigerian infant of otherwise healthy parents with no prior history of congenital anomalies who was born with left-sided cleft lip and palate, left anophthalmia, malformed left auricle, an atrial septal defect, and abnormal fusion of the medial ends of her ribs prior to their insertion into the sternum. She presented on account of respiratory difficulty following bouts of feed aspiration. Cautious feeding and the need for respiratory support are important aspects of care in patients with Goldenhar syndrome.
文摘A smooth and timely fitting of a visually appealing,custom-made eye prosthesis after the loss of an eye is not only essential from a cosmetic point of view but above all facilitates good social and psychological rehabilitation.Cryolite glass prostheses must be replaced at least once a year,PMMA prostheses polished once a year and renewed every five years.In children,especially in growth phases,the fit of the prosthesis should be checked at least every six months and adjusted,if necessary.Ocularists and ophthalmologists should determine an individual cleaning procedure together with the patient,which depends on both the prosthesis material and external factors.Complications such as allergic,giant papillary,viral,and bacterial conjunctivitis or even blepharoconjunctivitis sicca must be detected and treated at an early stage to avoid discomfort and to maintain the ability of prosthesis wear.In the case of inflammation-induced shrinkage of the conjunctival fornices or post-enucleation socket syndrome,surgical interventions are necessary.In summary,an early supply with an eye prosthesis,adequate treatment of complications,and attention to psychological aspects,form the basis for a successful long-term rehabilitation of anophthalmic patients.
文摘Sox2基因是SRY(sex determination region of Y chromosome)相关基因家族中的一员,是维持胚胎干细胞多能性和自我更新特性的关键转录因子之一。Sox2参与多种生物学过程,如调节细胞增殖和凋亡、参与肿瘤的形成和发展等。但关于Sox2基因在眼部疾病中作用研究的综述较少,为此,本文从Sox2基因的表达水平、相关信号通路及临床应用潜能等方面进行综述,以便于读者对Sox2基因在眼部疾病中的作用有更全面的认识和了解,开展更深入的研究。
基金supported by DBT-BUILDER-Cat III(Grant number:BT/INF/22/SP41403/2021)Gujarat State Biotechnology Mission(GSBTM)Gandhinagar,India,for financial assistance(Grant number:GSBTM/JD(R&D)/618/21e22/1224,Date:December 28,2021).
文摘Pesticides are reported to be teratogenic for non-target species.Our studies have unraveled the teratogenicity of 50%Chlorpyrifos&5%Cypermethrin combination(Ci)in developing chick embryos.A sublethal dose of this combination when administered to chick embryos,caused several developmental anomalies,with defects in eye development being frequent.Eye development begins at an early embryonic stage,with Sonic hedgehog(Shh)serving as a crucial signaling molecule.Shh plays a pivotal role in the early development of multiple organs,including the eye,by interacting with Pax6 and other regulatory molecules to guide the proper patterning of the eye.Thus,we hypothesized that Ci administration may lead to alteration in Shh expression which subsequently hampers downstream signaling molecules potentially contributing to congenital eye defects.Morphological,anatomical,histological,transcriptional and protein level analyses at various stages(Days 1,2,4 and 10)were carried out to evaluate the hypothesis.The results revealed a remarkable alteration of key regulators in treated embryos compared to control,providing insights into plausible causative mechanisms underlying Ciinduced congenital eye defects.
