Identification of pathogenic genes in a family with oculocutaneous albinism / 中华皮肤科杂志

Objective:To detect mutations in a pedigree containing two brothers with oculocutaneous albinism (OCA) by whole-exome sequencing and Sanger sequencing.Methods:Clinical data were collected from a pedigree with OCA, and DNA was extracted from peripheral blood samples obtained from the proband and other family members. The whole-exome coding region of the proband was directly sequenced by whole-exome sequencing technology to identify potential pathogenic mutations, and Sanger sequencing was conducted to verify the gene mutations.Results:Both the proband and his younger brother presented with generalized white skin, golden-yellow hair, bilateral nystagmus, photophobia, translucent iris, conjunctival congestion, and refractive errors of both eyes. The proband′s parents, grandparents, maternal grandparents, and children were all phenotypically normal, and his parents′ marriage was non-consanguineous. Three heterozygous mutations were identified in the OCA2 gene of both the proband and his younger brother, including a nonsense mutation c.1290T>A, and 2 missense mutations c.1363A>G and c.1204T>C. The mutation c.1204T>C has not been previously reported, and was a novel gene mutation in the OCA2 gene. In addition, 1 heterozygous mutation c.1204T>C was identified in the OCA2 gene in the proband′s father and daughter, 2 heterozygous mutations c.1290T>A and c.1363A>G were found in the OCA2 gene in the proband′s mother, and 1 heterozygous mutation c.1290T>A was identified in the OCA2 gene in the proband′s son and the daughter of the proband′s younger brother.Conclusions:Three gene mutations were identified in the OCA2 gene in the 2 patients with OCA, and the nonsense mutation c.1290T>A may be the pathogenic mutation causing the clinical phenotype of this family. These findings expand the pathogenic mutational spectrum of the OCA gene.

Prevalence of premalignant and malignant skin lesions in oculocutaneous albinism patients

SUMMARY OBJECTIVE: Oculocutaneous albinism describes a group of pigmentary disorders that lead to skin sensitivity and predisposition to skin malignances. Aims: To analyze clinical and epidemiological data in oculocutaneous albinism patients and to determine the prevalence of malignant skin lesions, assessing possible risk factors for skin cancer. METHODS: Cross-sectional study evaluating epidemiological data, habits of sun exposure and sun protection, and clinical examination of albino patients followed in a reference dermatology outpatient clinic in Brasil. Our primary outcome was the occurrence of malignant skin lesions in biopsied tissues. RESULTS: Of 74 patients analyzed, 11 (15%) had one or more suspicious lesions and were biopsied, of which 8 (72.7%) patients presented with basal cell carcinomas, 7 (63.3%) presented with squamous cell carcinoma, and 1 (9%) presented with melanoma. Moreover, 32(43%) patients presented with actinic keratosis. Age, female gender, previous history of sunburn, history of malignant lesions and history of sun exposure without photoprotection were associated with the presence of malignant lesions. Limitations: Unicentric, non-aleatory sample. CONCLUSIONS: There was a high prevalence of malignant and pre-malignant lesions in this population. Some potentially modifiable risk factors were associated with the occurrence of malignant skin lesions.

Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors

Abstract Oculocutaneous albinism is an autosomal recessive disease caused by the complete absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or absence of melanin, albinos are highly susceptible to the harmful effects of ultraviolet radiation and are at increased risk of actinic damage and skin cancer. In Brazil, as in other parts of the world, albinism remains a little known disorder, both in relation to epidemiological data and to phenotypic and genotypic variation. In several regions of the country, individuals with albinism have no access to resources or specialized medical care, and are often neglected and deprived of social inclusion. Brazil is a tropical country, with a high incidence of solar radiation during the year nationwide. Consequently, actinic damage and skin cancer occur early and have a high incidence in this population, often leading to premature death. Skin monitoring of these patients and immediate therapeutic interventions have a positive impact in reducing the morbidity and mortality associated with this condition. Health education is important to inform albinos and their families, the general population, educators, medical professionals, and public agencies about the particularities of this genetic condition. The aim of this article is to present a review of the epidemiological, clinical, genetic, and psychosocial characteristics of albinism, with a focus in skin changes caused by this rare pigmentation disorder.

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).

Mutation analysis in a pedigree with oculocutaneous albinism / 中华皮肤科杂志

Objective To investigate gene mutations in a pedigree with oculocutaneous albinism by using targeted next-generation sequencing technology.Methods Clinical data were collected from a pedigree with oculocutaneous albinism.Genomic DNA was extracted from peripheral blood cells of the proband and his parents.High-throughput sequencing technology was used for sequence analysis of coding regions in exons of 29 genes including TYR,OCA2,TYRP1 and SLC45A2 in the proband to find potential pathogenic gene mutations.Sanger sequencing was conducted to detect the corresponding genetic loci in the parents.Results Two heterozygous mutations were identified in the TYR gene of the proband,including a novel mutation c.534G ＞ C (p.Trp178Cys) and a known mutation c.1147G ＞ A (p.Asp383Asn).The detection of the TYR gene mutations in the parents of the proband showed that the c.534G ＞ C and c.1147G ＞ A mutations in the proband were inherited from his father and mother respectively.Conclusion A novel pathogenic mutation c.534G ＞ C in the TYR gene is identified in the pedigree with oculocutaneous albinism by using targeted next-generation sequencing technology.

Screening of TYR gene mutations and clinical classification in oculocutaneous albinism patients / 中华实验眼科杂志

Background Oculocutaneous albinism (OCA) is a hereditary disease of pigment absence in eyes,skin and hair due to the lack of congenital melanocyte.OCA is classified into 7 types based on different genetic mutations,and the mutation of tyrosinase (TYR) gene causes OCA type 1 (OCA1).OCA has obvious genetic heterogeneity and phenotypic heterogeneity.The molecular diagnosis of the mutant gene is helpful for the classification and molecular pathogenesis study of OCA.Objective This study was to screen the TYR mutation in OCA patients,and to analyze the association between the gene mutation type and clinical phenotype.Methods Ten patients with OCA were enrolled in Tianjin Ophthalmological Hospital from January 2011 to December 2014.The clinical and ocular manifestations of the patients were examined.Peripheral venous blood 3 ml was collected in the patients and their lineal relatives for the extraction of genomic DNA.Extracted DNA was amplified by PCR and the TYR gene sequence was analyzed,including all 5 exon coding sequence and exon 5 ' and 3' end and the non-coding region sequence of intron splicing in TYR gene.This study complied with Helsinki Declaration and the protocol was approved by Ethic Committee of Tianjin Eye Hospital.Informed consent was obtained from each subject.Results All the patients showed white or reddish hair and snow-white skin,and different degrees of pigment lack was seen in iris.The best corrected visual acuity of the patients was 0.05-0.2,and 3 patients complicated with nystagmus.Fundus findings showed a sunset-like change and dysplasia of macula.The TYR gene sequencing revealed that patient 1 was OCA1A subtype,with the compound heterozygous mutant of c.832C＞T (p.R278X) and c.1217C＞T (p.P406L),and his/her parents occurred the heterozygous mutation of exons P406L and R278X.The phenotype of the patient 1 was white hair and white iris.The patient 3 was OCA1B subtype,with the compound heterozygous mutations of c.1265G＞A (p.R422Q) and c.1217C＞T (p.P406L),showing an appearance of reddish brown hair and sallow iris.TYR gene mutant was not detected in other 8 patients.Conclusions The mutation of TYR gene is the main cause of OCA1 type.The phenotype of OCA1A subtype is no pigment in eyes and hair,and one of OCA1B subtype was obviously lessening of pigment.The difference of mutant genes of OCA is the cause of genetic and phenotypic heterogeneity.

Quality of life in patients with oculocutaneous albinism

AbstractBACKGROUND:The social reality of the albino needs to be more studied in Brazil, as myths and social segregation regarding this illness are likely to be found in the country, with psychosocial and medical implications.OBJECTIVE:As this subject has not been referenced in previous scientific articles in Brazil, this research intends to evaluate the quality of life of the albinos that treated at our medical institution.METHODS:The quality of life was evaluated through the WHOQOL-BREF. Furthermore, two aspects of main relevance in the lives of the albinos were also objects of research, low vision and skin cancer. The sample consisted of forty oculocutaneous albinos and a control group of forty healthy individuals, matched by sex and age.RESULTS:Among the participants, 57.7% were between 18 and 40 years old, 28.2% were between 41 and 60, and 14.1% were over 60. 42.1% had skin cancer before the study, 18.4% had skin cancer during the study and 89.5% stated visual deficit. The results obtained in the questionnaires showed a statistically significant difference in the physical domain, with P < 0.001.CONCLUSION:Low vision combined with skin lesions and social stigma may contribute to disturbances in the quality of life of oculocutaneous albinos. The results presented in this study demonstrated the vulnerability of the affected individuals and the special care required by those patients, at the same time that the need for further research is highlighted in order to better elucidate the aspects related to albinism.