Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene

Dear Sir,Iam Haiba Kaul,from the Department of Biochemistry,University of Health Sciences,Lahore,Pakistan.I write to present a study of oculocutaneous albinism（OCA）in consanguineous Pakistani families.OCA is a genetic defect of melanin biosynthesis that mainly affects eyes,skin and hair.

Comment on homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene

Dear Editor,I have carefully read the article entitled ＂Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene＂,published by Shakil et al in 2016 and found it very interesting for the scientific community.

Correlation of Macular Thickness, Multifocal ERG with Visual Acuity in Oculocutaneous Albinism (OCA)

Background and Aim: Ocular albinism is known to have nystagmus and foveal hypoplasia. A study was done to evaluate the correlation of visual acuity with macular thickness (MT) and mf ERG. Materials and Methods: A total of 20 eyes (10 patients) with OCA were selected. Macular thickness was evaluated with optical coherence tomography and mf ERG was done in all the patients. Results: Mean age was 16.1 ± 7.3 years. The patients were divided into three groups based on their visual acuity > 6/12 (group A), 6/18 - 6/24 (group B), 6/36 or less (group C). Mean MT in patients with visual acuity in group A, B and C was 194.8 ± 26.7, 220 ± 12.3 and 243.5 ± 17.3 microns respectively. The amplitudes of first positive wave (P1) and first negative wave (N1) for the central ring in mf ERG in patients of group A, B and C was 1.1 ± 0.5 (P1), 0.7 ± 0.2 (N1), 0.6 ± 0.5 (P1), 0.3 ± 0.2 (N1), 0.7 ± 0.2 (P1), 0.3 ± 0.1 (N1) microvolts respectively. The vision correlated well with the macular thickness. The mf ERG potentials (P1 and N1) do not correlate with the visual acuity. Conclusion: We believe that the visual acuity in albinotic patients is affected by the macular thickness but the electric potentials do not depend on the visual acuity.

Effect of prisms on visual acuity,contrast sensitivity and nystagmus in patients with albinism

AIM:To investigate the effect of using base-out prisms on nystagmus,visual acuity and contrast sensitivity in patients with albinism.METHODS:In this interventional study,patients with albinism who had nystagmus were enrolled.A comprehensive eye exam was conducted,which included refraction,assessment of far and near vision acuity,and contrast sensitivity measurements.To check for the nystagmus,a videonystagmography was used.The tests were carried out in three modes:without any correction,with optical correction,and with correction using base-out prisms in three different powers,including 4,6,and 8 prism diopters.RESULTS:Totally 23 patients with average age of 28.65±12.13 were examined.It was found that the use of optical correction and optical correction with prisms resulted in a statistically significant improvement in both far(at least:P<0.006)and near visual acuity(at least:P<0.001 except for prism 8;P<0.02).In addition,contrast sensitivity significantly improved at all low and medium frequencies except for correction with prism 8 in frequency 1.5(at least:P<0.01 except for prism 4,frequency 6;P=0.04).no significant improvement was observed in the evaluation of nystagmus characteristics.CONCLUSION:Optical correction with a prism can improve visual acuity and some spatial frequencies,but failed to improve nystagmus parameters.

Genetic analyses of Chinese patients with digenic oculocutaneous albinism

Background Oculocutaneous albinism （OCA） is a heterogeneous and autosomal recessive disorder in all populations worldwide. The mutational spectra of OCA are population-specific. Some OCA patients carry mutations from different OCA genes. In this study, we investigated the frequency of digenic mutations in Chinese OCA patients. Methods Genomic DNAs were extracted from the blood samples of 184 clinically diagnosed OCA patients and 120 unaffected subjects. The amplified DNA segments of the exons and exon-intron boundaries were screened for mutations of TYR, OCA2, TYRP1, SLC45A2, and HPS1 by direct sequencing. To exclude the previously unidentified alleles from polymorphisms, samples from 120 unaffected controls were sequenced for the same regions of variations. Results In all 184 patients, 134 had two pathologic mutations on one locus. Eleven cases had no apparent pathologic mutations in any of the genes studied. Among the remaining 39 patients who had only one pathologic mutation, five patients （2.7% in total） were found to carry the mutational alleles on a second locus in TYR, OCA2 or SLC45A2. Of the five digenic OCA patients, four patients were clinically diagnosed as OCA2 and one patient as OCAI. A previous unidentified allele p.G188D in SLC45A2 was identified, which was not present in the 120 unaffected controls. Conclusions The identification of the digenic OCA patients suggests the synergistic roles among TYR, OCA2 and SLC45A2 during melanin biosynthesis, which may cause OCA under digenic mutations. This information will be useful for gene diagnosis and genetic counseling of OCA in China.

A novel missense mutation of the TYR gene in a pedigree with oculocutaneous albinism type 1 from China

Background The mutation of the tyrosinase （TYR） gene results in oculocutaneous albinism type 1 （OCA1）, an autosomal recessive genetic disorder. OCA1 is the most common type of OCA in the Chinese population. Hence, the TYR gene was tested in this study. We also delineated the genetic analysis of OCA1 in a Chinese family. Methods Genomic DNA was isolated from the blood leukocytes of a proband and his family. Mutational analysis at the TYR locus by DNA sequencing was used to screen five exons, including the intron/exon junctions. A pedigree chart was drawn and the fundus of the eyes of the proband was also examined. Results A novel missense mutation p.1151S on exon 1, and homozygous TYR mutant alleles were identified in the proband. None of the mutants was identified among the 100 normal control subjects. Genetic analysis of the proband＇s wife showed normal alleles in the TYR gene. Thus, the fetus was predicated a carrier of OCA1 with a normal appearance. Conclusion This study provided new information about a novel mutation, p.1151S, in the TYR gene in a Chinese family with OCAI. Further investigation of the proband would be helpful to determine the effects of this mutation on TYR activity.

Prenatal Genotyping of Four Common Oculocutaneous Albinism Genes in 51 Chinese Families

Oculocutaneous albinism（OCA） is an autosomal recessive disorder characterized by hypopigmentation in eyes,hair and skin,accompanied with vision loss.Currently,six genes have been identified as causative genes for non-syndromic OCA（OCA-1w4,6,7）,and ten genes for syndromic OCA（HPS-1e9,CHS-1）.Genetic counseling of 51 Chinese OCA families（39 OCA-1 with mutations in the TYR gene,6 OCA-2 with mutations in the OCA2 gene,4 OCA-4 with mutations in the SLC45A2 gene,1 HPS-1（Hermanskye Pudlak syndrome-1） with mutation in the HPS1 gene,and 1 mixed OCA-1 and OCA-4） led us to perform the prenatal genetic testing of OCA using amniotic fluid cells through the implementation of our optimized strategy.In our cohort,eleven previously unidentified alleles（PUAs）（5 in TYR,2 in OCA2,and 4 in SLC45A2） were found.Three missense PUAs（p.C112 R,p.H363 R and p.G379 V of TYR） and one in-frame deletional PUA（p.S222 del of SLC24A5） led to fetuses with OCA when co-inherited with other disease causative alleles.Three PUAs（p.P152 H and p.W272 X of TYR,p.A486 T of SLC24A5） identified in the OCA probands did not co-transmit with known pathological alleles and thus gave rise to unaffected fetuses.Four PUAs（p.Q83 X and p.A658 T of TYR,p.G161 R and p.G366 R of SLC24A5） did not transmit to the unaffected fetuses.In addition,the in vitro transfection assays showed that the p.S192 Y variant of TYR produced less pigment compared to the wild-type allele.A fetus with a digenic carrier of OCA-1 and OCA-4 was unaffected.In combination with functional assays,the family inheritance pattern is useful for the evaluation of pathogenicity of PUAs and genetic counseling of OCA.

Application of multiplex ligation-dependent probe amplification in the genetic testing of oculocutaneous albinism

To the Editor: Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by a group of mutations related to the regulation of melanin synthesis and melanosome biogenesis. The prevalence of OCA worldwide is approximately 1 in 17,000.[1] Other than symptomatic treatment, there is no effective treatment for albinism. Due to the variability in clinical phenotypes, it is difficult to classify sub-types simply by clinical features;therefore, molecular and genetic analyses are the most reliable methods for confirming diagnosis, carrier screening, and pre-natal diagnosis.

Oculocutaneous Albinism with Squamous Cell Carcinoma, Bowen’s Disease and Actinic Keratosis: A Case Report

IntroductionOculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by defects in melanin synthesis that affect the skin,eyes,ears,and hair to varying degrees.Because of the melanin deficiency,albino patients are at high risk for sun-induced skin cancers.Herein,we report a rare case of an OCA type 4 combined with a progressive carcinogenesis for precancerous (actinic keratosis,AK),in situ (Bowen's disease),and invasive status of squamous cell carcinoma (SCC).

QTL Detection for Albinism-Related Loci in Chinese Tongue Sole(Cynoglossus semilaevis)

The Chinese tongue sole(Cynoglossus semilaevis) is widely cultured in the coastal region of East Asia and has excellent economic value. However, the high albino rate of the breeding population has caused a significant loss to the aquaculture industry. To study the molecular mechanism of albinism, the present study used an albino Chinese tongue sole family to construct three simple sequence repeat(SSR) linkage groups, and draft a preliminary linkage map related to albinism. After albinism-related loci mapping, 18 albinism-related loci were detected under two models(containing 2407 genes) compared to the Chinese tongue sole genome. One of these loci, the tyrosinase related protein(tyrp2), which has been reported previously as an important gene regulating both eumelanin and phaeomelanin levels, was indicated to be the possible cause of albinism. Thirty-five Gene Ontology(GO) terms and 14 Kyoto Encyclopedia of Genes and Genome pathways were annotated via bioinformatic analyses. One GO term with protein tyrosine kinase activity, which contained 10 genes, was previously suggested to affect fish albinism. These results establish a foundation for further in-depth study of albinism in Chinese tongue sole.

The tyrosinase gene family and albinism in fish

Tyrosinase exists universally in organisms and is a characteristic enzyme of melanocytes. Tyrosinase family genes in vertebrates consist of 3 related members; tyrosinase （TYR, Tyr）, tyro sinase-related protein-1 （TRP-1, Tyrp 1）, and tyro sinase-related protein-2 （TRP-2, Tyrp2, Dct）. These proteins catalyze melanin biosynthesis in pigment cells and play important roles in determining vertebrate coloration. Transcription of the TYR and TRP genes is useful for studying neural crest and optic vesicle cell migration and differentiation during emblyogenesis and important in pigment rescue in fish. In this paper, the structure of gene and protein molecular evolution, function and roles of the TYR family in fish were reviewed.

The Detection of Partial Albinism at Three Species of Bats (Mammalia: Chiroptera) in European Part of Russia

The first time for the territory of European Russia describes the cases of catching bats with signs of albinism. This article describes the detection of three species of bats with partial albinism in European part of Russia. There are four animal units of Eptesicus serotinus turcomanus that are stored in Penza State University. They were procured in Astrahan region in 1992 and in 1996. One more animal was found in Volgograd region in 2004. All these animals have white spots of different size and shape on their abdominal part of body. In 2012 it was caught a young female of Pipistrellus nathusii in Samarskaya Luka (Samara region) and in 2013 the scientists found a mature female of Myotis mystacinus. Both animals had a light-colored fur, red eyes and with almost white ears. Moreover, they had pale-pink noses and extremities.

Studies Shed Light on the Albinism Gene of Rhesus Monkey

A recent study by researchers at the Kunming Institute of Zoology (KIZ) of the Chinese Academy of Sciences (CAS) identifies the albinism gene of rhesus monkeys using the method of molecular technology, and suggests the age of the albinism gene in rhesus monkeys should be roughly 800,000 years. The general albinism

一例东北马鹿白化病的病例分析

为了探究一只东北马鹿的白化病的遗传机制,对其进行了30全基因组重测序及生物信息分析并进行验证。结果表明。通过筛选与白化病致病基因相关的SNPs,最终定位到这只白化马鹿的5个SNPs,分别涉及到HPS3(c.A1652G),LYST(c.C3338T、c.G3635A、c.C4613T),TYR(c.C1204T)3个基因。同源蛋白序列分析排除了HPS3和LYST上突变位点的致病性,而TYR基因上为终止突变。RT-PCR分析进一步证实TYR基因的终止突变,蛋白结构预测分析显示,TYR基因的突变位点位于蛋白的胞质区与跨膜区之间,而作为与网格衔接蛋白AP-3接合的双亮氨酸基序(EEXXXPLL)位于膜内区,因突变而丢失。综上分析,TYR基因(c.C1204T)突变导致了马鹿的白化病。该突变使TYR尾端丢失,包含了双亮氨酸基序和跨膜区丢失,TYR蛋白无法从内质网转移到黑素体上,黑素体功能性缺失导致白化病。

OCA2基因c.1441G>A(p.Ala481Thr)位点变异的生育遗传咨询探讨

目的对OCA2基因c.1441G>A(p.Ala481Thr)位点变异白化病家系的遗传咨询和生育指导。方法丈夫,26岁,轻度白化病表现,毛发偏黄,皮肤白皙,视力正常,无白化病相关系统受累表现。妻子,27岁,G_(0)P_(0),身体良好。夫妇属非近亲婚配。现备孕咨询,评估生育白化病患儿风险。遗传咨询后,建议其进行遗传性白化病相关基因的测序检测。以“OCA2基因,c.1441G>A位点”为检索词,检索Pubmed、OMIM、Clinvar数据库、中国知网、万方数据库(建库至2023年10月),选取OCA2基因c.1441G>A(p.Ala481Thr)变异相关的白化病病例相关资料文献。结果结果显示,丈夫OCA2基因存在2个变异,分别为NM_000275.3:c.182G>A(p.Trp61*)和NM_000275.3:c.1426A>G(p.Asn476Asp),妻子OCA2基因有1个杂合变异,为NM_000275.3:c.1441G>A(p.Ala481Thr)。Sanger溯源验证,丈夫所携无义变异c.182G>A(p.Trp61*)来源其母亲,所携错义变异c.1426A>G(p.Asn476Asp)变异来源其父亲。妻子所携错义变异c.1441G>A(p.Ala481Thr)并非来源其父亲,其母亲信息不详。使用数据库搜索c.1441G>A变异的表型效应,得知c.1441G>A(p.Ala481Thr)属于一种亚等效变异,Ala481Thr在黑色素形成中有70%的野生型功能,纯合子无表现,表型正常。据c.1441G>A的亚等效作用,遗传咨询后,夫妇知情同意选择自然怀孕方式。随访这对夫妇怀孕并分娩1表型正常女儿。经测序验证,女儿遗传了父亲c.1426A>G(p.Asn476Asp)变异和母亲正常OCA2基因。结论报道一例白化病OCA2基因c.1441G>A变异相关的生育遗传咨询案例,复习文献,总结c.1441G>A(p.Ala481Thr)白化病的亚等效作用所产生的表型特异性,帮助临床医生正确认识合理运用恰当的遗传学检测手段和深刻理解临床决策前充分遗传咨询的重要性,从而提高对该类变异的遗传咨询能力,有效地避免了过度医疗。

鼻咽癌伴白化病治疗后皮肤色素沉着1例报告

鼻咽癌是发生于鼻咽部黏膜上皮的恶性肿瘤,发病多与EB病毒感染相关^([1])。放疗是鼻咽癌治疗的重要手段之一^([2])。白化病是由基因突变所致黑色素生成减少或缺陷引起的一种无法治愈的常染色体隐性疾病,多以全身皮肤和毛发的色素沉着普遍减少为特征,缺乏有效的治疗手段^([3])。目前未见国内外关于鼻咽鳞癌伴白化病的相关报道,现将我院1例鼻咽癌伴白化病的患者诊疗过程报道如下。

审美规训下文化表征的偏向——以音乐短片《美丽的伤痛》对白化病人的呈现为例

审美标准是社会规训的产物,时尚模特作为审美标准的具体呈现,他们的媒介可见性塑造了社会对其代表群体的刻板印象和普遍期待,是审美规训下的特殊文化表征。近年来,国际时尚界发起一场旨在推广多元审美的“模特化运动”,部分白化病人成为新审美标准的代言人,打破了往昔大众媒介对其负面的刻板印象。音乐短片《美丽的伤痛》作为典型例子,通过片中特邀嘉宾肖恩的角色设置和形象呈现以及与女主角的对比,可以发现白化病模特肖恩在片内、片外受到时尚行业的双重认可,为参照群体发挥示范效应,其背后的根源在于西方优势阶层的文化授权。肖恩的白化外貌高度符合西方主流审美价值观,适应了西方文化霸权中对苍白美的追求和对差异美的利用。因此,时尚产业出于隐性的文化偏见和权力诉求将其塑造为一种符号性商品。这种策略实质上蕴含着对白化外貌的过度强调和价值极化,是对白化病人群的异化,存在破坏其自主性、剥夺其发声权、孕育新文化偏见的风险。

白化红点齿蟾蝌蚪皮肤的转录组学分析

为探究喀斯特洞穴的代表物种——红点齿蟾蝌蚪(Oreolalax rhodostigmatus)白化的分子调控机制,采用Illumina HiSeqTM4000对白化和黑色红点齿蟾蝌蚪皮肤组织进行了转录组测序,探寻基因表达差异,为红点齿蟾适应性进化提供理论依据。结果显示,转录组拼接组装后获得98711个Unigene,总长度为96459902 bp,平均长度为977 bp;共预测3389个完整开放阅读框(open reading frame,ORF),其中长度分布在0~200个氨基酸的ORF最多,占ORF总数的74.89%。Deseq2分析共筛选出269个差异表达基因(DEGs),其中上调基因136个,下调基因133个。GO功能注释发现,差异表达基因显著富集在细胞过程、代谢过程、结合、催化活性等通路上。KEGG(Kyoto Encyclopedia of Genes and Genomes)信号通路分析显示,差异基因被成功富集到175个信号通路上,主要包括代谢途径、脂肪酸合成、酪氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢等通路,筛选到酪氨酸代谢通路、黑色素合成通路、MAPK信号通路、WNT信号通路、PI3K-Akt信号通路与黑色素合成相关。通过荧光定量PCR验证转录组数据的可靠性。最后利用MISA查找到9623个SSR位点,出现频率最高的为二碱基重复(79.87%)。本实验结果可为红点齿蟾蝌蚪白化性状相关基因的挖掘与功能研究提供基础信息。

湖南发现一白化北红尾鸲

2023年3月31日,在湖南省湘西土家族苗族自治州永顺县小溪国家级自然保护区开展全省生物多样性专项调查时,观察到1只雀形目(Passeriformes)白化鸟类。经鉴定以及比较分析该鸟种为雌性北红尾鸲(Phoenicurus auroreus),判断为局部白化个体。

基于共现网络分析和预测白化病共表型的研究

目的分析白化病表型特征及其关联性。方法从PubMed数据库中获取2023年6月10日前白化病相关研究文献,从其摘要文本中抽取表型实体,构建表型共现网络。采用GePhi和VOSviewer软件分析网络的整体特征和表型聚类情况。采用Apriori算法挖掘表型间的关联规则。使用AA指数进行链路预测,预测可能的白化病表型组合。结果白化病表型共现网络具有小世界特性,眼球震颤、皮肤色素减退和视网膜中央凹发育不良是其主要表型。白化病表型异常主要分为5大类,包括视觉系统异常、免疫系统异常、皮肤和毛发系统异常、神经系统异常、呼吸和消化系统异常。多种眼部异常均与眼球震颤共现。白化病可能出现的异常表型组合包括肺炎与皮肤色素减退、视网膜中央凹发育不良和视神经萎缩等表型组合。结论预测并分析白化病的表型特征及表型间的关联规律,以及白化病患者可能出现的表型共现情况,可为确定白化病的研究方向及识别、诊断、预判白化病的发展提供有效参考。