Spectrum Analysis of Albinism Genes in a Large Cohort of Chinese Index Patients

Wei, Aihua; Zhang, Tianjiao; Yuan, Yefeng; Zhan, Qimin; Bai, Dayong; Zhang, Yingzi; Zhang, Yunlan; Teng, Liu; Huang, Qiaorong; Yang, Xiumin; Li, Wei

doi:10.1016/j.jid.2021.11.014

Cited by 9 publications

(3 citation statements)

References 20 publications

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“…There were no relevant amino acid changes in the c.2267-2 A > C mutation, and we did not perform conserved analyses and protein 3D structure prediction. It has been reported in the literature that a change in the receptor site from AG to CG in intron 22 of OCA2 resulted in a predicted lack of splicing site recognition, which may have affected the splicing of OCA2 mRNA [ 26 , 27 ]. In the p.G420R mutation, the Pro420 residue is located in the coil of the 3D structure of the protein, a site that is highly conserved in several species.…”

Section: Resultsmentioning

confidence: 99%

Genetic analysis of albinism caused by compound heterozygous mutations of the OCA2 gene in a Chinese family

Wang,

Chang,

Gao

et al. 2024

Hereditas

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Background Oculocutaneous albinism (OCA) is a group of rare genetic disorders characterized by a reduced or complete lack of melanin in the skin, hair, and eyes. Patients present with colorless retina, pale pink iris, and pupil, and fear of light. The skin, eyebrows, hair, and other body hair are white or yellowish-white. These conditions are caused by mutations in specific genes necessary for the production of melanin. OCA is divided into eight clinical types (OCA1-8), each with different clinical phenotypes and potential genetic factors. This study aimed to identify the genetic causes of non-syndromic OCA in a Chinese Han family. Methods We performed a comprehensive clinical examination of family members, screened for mutation loci using whole exome sequencing (WES) technology, and predicted mutations using In silico tools. Results The patient’s clinical manifestations were white skin, yellow hair, a few freckles on the cheeks and bridge of the nose, decreased vision, blue iris, poorly defined optic disk borders, pigmentation of the fundus being insufficient, and significant vascular exposure. The WES test results indicate that the patient has compound heterozygous mutations in the OCA2 gene (c.1258G > A (p.G420R), c.1441G > A (p.A481T), and c.2267-2 A > C), respectively, originating from her parents. Among them, c.1258G > A (p.G420R) is a de novo mutation with pathogenic. Our analysis suggests that compound heterozygous mutations in the OCA2 gene are the primary cause of the disease in this patient. Conclusions The widespread application of next-generation sequencing technologies such as WES in clinical practice can effectively replace conventional detection methods and assist in the diagnosis of clinical diseases more quickly and accurately. The newly discovered c.1258G > A (p.G420R) mutation can update and expand the gene mutation spectrum of OCA2-type albinism.

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Section: Resultsmentioning

confidence: 99%

Genetic analysis of albinism caused by compound heterozygous mutations of the OCA2 gene in a Chinese family

Wang,

Chang,

Gao

et al. 2024

Hereditas

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“…Goto M. et al found that the variant of TYR :c.[1037‐10_1037‐9delTT;1037–7 T > A] caused the insertion of four bases (ACAG) upstream of the common acceptor site of exon 3, leading to a premature termination codon in the downstream (Goto et al, 2004). Although TYR :c.1037–7 T > A has been reported in some populations with OCA1 (Ko et al, 2012; Lasseaux et al, 2018; Lin et al, 2014; Matsunaga et al, 1999; Park et al, 1997; Wang et al, 2015; Wei et al, 2022), the biological consequences of this variant are not known. We verified that TYR :c.1037–7 T > A was a splicing variant and resulted in an insertion of five bases (AACAG) in the mRNA transcript with a splicing experiment.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of the compound heterozygous variants of TYR gene in a northern Chinese family with Oculocutaneous albinism type 1

Jia

et al. 2023

Pigment Cell Melanoma Res

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Oculocutaneous albinism (OCA) is a genetically heterogeneous disease and is most inherited in an autosomal recessive manner. The characteristic manifestation of OCA is due to disfunction of melanin synthesis. OCA1 is the most severe subtype of OCA and is caused by homozygous or compound heterozygous variants in tyrosinase (TYR) gene, which is the key gene for melanin synthesis. This study aimed to identify the genetic variants of a northern Chinese family with OCA1. Clinical information and peripheral blood samples were collected. PCR amplification and Sanger sequencing were used to detect the entire exons and adjacent flanking sequences of TYR gene. Functional prediction of variants was performed by various bioinformatic analyses, while the pathogenicity classification of variants was evaluated according to ACMG standards and guidelines. A missense variant NM_000372.5:c.107G > C;NP_000363.1:p.C36S was discovered in TYR gene which converted cysteine to serine. Another variant in intron, NM_000372.5:c.1037–7 T > A, also affected the function of TYR gene. We verified the pathogenicity of the intron variant with a pCAS2 mini‐gene based splicing assay and found that c.1037–7 T > A led to an insertion of 5 bp upstream from the common acceptor site of exon 3, which caused a frameshift TYR:c.1037–7 T > A:p.G346Efs*11. The results showed that the compound heterozygous variants c.107G > C:p.C36S and c.1037–7 T > A:p.G346Efs*11 of TYR gene were the pathogenic variants for this OCA1 family.

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“…New genes associated with albinism have recently been discovered, in both oculocutaneous and syndromic forms [ 2 , 3 ]. Thus, albinism and its many forms have been widely investigated in genetics [ 4 – 6 ], but psychological studies on albinism life experiences are quite limited, having been mainly led on the African continent, and the results are often not generalizable [ 7 ]. In addition, many of the papers on albinism are in the form of essays, testimonies, or pleadings [ 8 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

The experience of albinism in France: a qualitative study on dyads of parents and their adult child with albinism

Fournier,

Hasdenteufel,

Garrouteigt

et al. 2024

BMC Med

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Background To date, almost no research on the psychosocial implications of albinism has been conducted in France and an exploration of albinism-related experiences could be beneficial, in order to better understand this condition. The aim of this study was to examine how French people with albinism and their parents live with and adapt to this condition in all the areas of their lives. Methods Semi-structured phone interviews were conducted with 9 parent-child dyads, each participating separately. Participants were recruited by convenience sampling, thanks to the combined efforts of a patient association (Genespoir) and professionals from the partner medical referral centers involved in the project. Dyads in which the individual with albinism had any comorbidity were excluded. The interviews were then transcribed and subjected to in-depth thematic analysis. Two codebooks were constructed in a mirrored process: one for people with albinism; the other for their parents. They were finally merged at the end of the coding step. Results Four main categories were identified: personal perceptions and social representations of albinism, difficulties and obstacles encountered by people with albinism, resources and facilitators, and the importance of parent-child functioning. The results indicated that experiences of stigmatization during childhood and adolescence are common and that people with albinism face challenges in adapting to certain obstacles related to their visual impairments (VI) (e.g., inability to drive a car; eye strain...). Parents emerged as one, if not as the main, source of support for people with albinism throughout their development. Although external support systems exist to assist them in various aspects of their lives, some of them primarily rely on their own personal resources to cope. Conclusions This research highlights the importance of a systemic and transdisciplinary approach to make sure families receive the support that best meets their needs.

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Spectrum Analysis of Albinism Genes in a Large Cohort of Chinese Index Patients

Cited by 9 publications

References 20 publications

Genetic analysis of albinism caused by compound heterozygous mutations of the OCA2 gene in a Chinese family

Genetic analysis of albinism caused by compound heterozygous mutations of the OCA2 gene in a Chinese family

Identification and characterization of the compound heterozygous variants of TYR gene in a northern Chinese family with Oculocutaneous albinism type 1

The experience of albinism in France: a qualitative study on dyads of parents and their adult child with albinism

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