OCA1 in Different Ethnic Groups of India is Primarily Due to Founder Mutations in the Tyrosinase Gene

Chaki, Moumita; Sengupta, Mainak; Mukhopadhyay, Arijit; Rao, Subba; Majumder, Partha P.; Das, Madhusudan; Samanta, Samiran; Ray, Kunal

doi:10.1111/j.1469-1809.2006.00247.x

Cited by 34 publications

(42 citation statements)

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“…According to our current knowledge, 10–25% of the isolated and syndromic OCA cases are not explained by paired, trans-oriented mutations in known genes [34, 35]. Based on our results and the results of previous studies [22], we suggest that screening non-Mendelian OCA-associated genes might elucidate the causative genetic variant for these cases.…”

Section: Discussionsupporting

confidence: 63%

Delineating the genetic heterogeneity of OCA in Hungarian patients

et al. 2017

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BackgroundOculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities characterized by variable hair, skin, and ocular hypopigmentation. Six known genes and a locus on human chromosome 4q24 have been implicated in the etiology of isolated OCA forms (OCA 1–7).MethodsThe most frequent OCA types among Caucasians are OCA1, OCA2, and OCA4. We aimed to investigate genes responsible for the development of these OCA forms in Hungarian OCA patients (n = 13). Mutation screening and polymorphism analysis were performed by direct sequencing on TYR, OCA2, SLC45A2 genes.ResultsAlthough the clinical features of the investigated Hungarian OCA patients were identical, the molecular genetic data suggested OCA1 subtype in eight cases and OCA4 subtype in two cases. The molecular diagnosis was not clearly identifiable in three cases. In four patients, two different heterozygous known pathogenic or predicted to be pathogenic mutations were present. Seven patients had only one pathogenic mutation, which was associated with non-pathogenic variants in six cases. In two patients no pathogenic mutation was identified.ConclusionsOur results suggest that the concomitant screening of the non-pathogenic variants—which alone do not cause the development of OCA, but might have clinical significance in association with a pathogenic variant—is important. Our results also show significant variation in the disease spectrum compared to other populations. These data also confirm that the concomitant analysis of OCA genes is critical, providing new insights to the phenotypic diversity of OCA and expanding the mutation spectrum of OCA genes in Hungarian patients.

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Section: Discussionsupporting

confidence: 63%

Delineating the genetic heterogeneity of OCA in Hungarian patients

et al. 2017

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“…Interestingly, the p.R299H mutation of TYR ranks as the most frequent allele in Chinese (Table 2), Caucasians (Tripathi et al, 1992), Koreans (Park et al, 1997), and Christian Arabs (Zahed et al, 2005), suggesting that it is a common mutational allele in human OCA1. Both the c.929insC and p.R278X alleles in TYR have been reported in some Asian populations (Tripathi et al, 1993;Park et al, 1997;Tomita, 2000;Chaki et al, 2005a). Several mutations of TYR with higher allelic frequencies, such as p.W400L (Lin et al, 2006), c.232insGGG (Tsai et al, 1999), and p.C24Y (Wang et al, 2009a), have to date been reported only in Chinese OCA patients.…”

Section: Discussionmentioning

confidence: 93%

A Comprehensive Analysis Reveals Mutational Spectra and Common Alleles in Chinese Patients with Oculocutaneous Albinism

Wei

Wang

Long

et al. 2010

Journal of Investigative Dermatology

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Oculocutaneous albinism (OCA) is a heterogeneous recessive disorder with hypopigmentation in the skin, hair, and eyes. At least 16 genes have been identified as causative genes for human OCA. No comprehensive analysis has been conducted to study the spectral distribution of OCA in Chinese patients. We screened 127 unrelated and unselected Chinese OCA patients for mutations in the TYR, OCA2, TYRP1, SLC45A2, and HPS1 genes. We found that the spectrum of mutational genes and alleles of OCA is population specific. OCA1 is the most common (70.1% of cases) form of Chinese OCA, whereas OCA2, OCA4, and HPS1 account for 10.2%, 12.6%, and 1.6%, respectively. No apparent pathological mutation of TYRP1 has been found. Thirty-eight previously unreported mutational alleles were identified from these OCA patients and were not found in 100 nonalbinism subjects. Of the TYR mutational alleles, 81.1% were clustered on exons 1 and 2. Ten common alleles account for 74.6% of the mutational TYR alleles in Chinese OCA1 patients. The p.D160H allele accounts for 55.6% of the mutational SLC45A2 alleles in Chinese OCA4 patients. These results provide useful information for the establishment of an optimized strategy of gene diagnosis and genetic counseling of Chinese OCA patients.

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“…Las mutaciones G47D y 1379delTT han sido reportadas en diferentes lugares del mundo y ambas son responsables de albinismo óculo-cutáneo 1A, bien sea en forma homocigota o heterocigota compuesta. La mutación G47D se ha reportado en población de judíos marroquíes y sefarditas (26), en las Islas Canarias y Puerto Rico (24), México, Cuba y en caucásicos de origen no hispano residentes en Estados Unidos (8,27,28), mientras que la mutación 1379delTT ha sido únicamente reportada en población bengalí occidental en la India (21,22).…”

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Una mirada al albinismo óculo-cutáneo: reporte de mutaciones en el gen TYR en cinco individuos colombianos

et al. 2012

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Introducción. El albinismo óculo-cutáneo es un trastorno hereditario autosómico recesivo relacionado con la pigmentación. Sus manifestaciones clínicas incluyen hipopigmentación en piel, cabello y ojos, hipoplasia en la fóvea y disminución de la agudeza visual. A nivel mundial, hasta el momento, se han reportado, aproximadamente, 230 mutaciones en el gen TYR que causan albinismo óculo-cutáneo de tipo 1. Este gen codifica para la tirosinasa, enzima principal de la biosíntesis de melanina. Objetivos. Identificar las mutaciones en el gen TYR responsables del albinismo óculo-cutáneo de tipo 1 en cinco individuos colombianos; cuatro de ellos pertenecen a una misma familia y el otro individuo es un caso aislado no relacionado con la familia. Asimismo, se pretende evaluar un sistema oftálmico que permite corregir problemas de refracción, y disminuir el nistagmo y la fotofobia en uno de los casos. Materiales y métodos. Se hizo la secuenciación de los cinco exones del gen TYR en los cinco individuos de estudio y se buscaron portadores en la familia. Se llevó a cabo la evaluación clínica oftalmológica y la implementación del sistema correctivo en uno de los pacientes.Resultados. Se encontraron las mutaciones G47D y 1379delTT en la familia, y en el caso aislado, las mutaciones G47D y D42N. Con la implementación del sistema óculo-visual se logró incrementar la agudeza visual y disminuir el nistagmo. Conclusiones. Por ser el primer estudio en albinismo de este carácter en el país, estos resultados marcan una pauta para estudios posteriores de tamización molecular de albinismo en población colombiana.Palabras clave: albinismo oculo-cutáneo, monofenol monooxigenasa, mutación, lentes de contacto, Colombia An overview of oculocutaneous albinism: TYR gene mutations in five Colombian individualsIntroduction. Oculocutaneus albinism is a pigment-related inherited disorder characterized by hypopigmentation of the skin, hair and eyes, foveal hypoplasia and low vision. To date, 230 mutations in the TYR gene have been reported as responsible for oculocutaneus albinism type 1 worldwide. TYR gene encodes the enzyme tyrosinase involved in the metabolic pathway of melanin synthesis. Objectives. Mutations were identified in the TYR gene as responsible for oculocutaneous albinism type 1 in five Colombian individuals, and a new ophthalmic system was tested that corrected visual defects and symptoms in a patient with oculocutaneous albinism. Materials and methods. Samples were taken from 5 individuals, four of whom belong to a single family, along with a fifth individual not related to the family. Five exons in the TYR gene were sequenced to search for the gene carriers in the family and in the non-related individual. In addition, clinical ophthalmological evaluation and implementation of an new oculo-visual system was undertaken. Results. A G47D and 1379delTT mutation was identified in the family. The unrelated individual carried a compound heterozygote for the G47D and D42N mutations. The oculo-visual corrective system was able to increase vis...

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OCA1 in Different Ethnic Groups of India is Primarily Due to Founder Mutations in the Tyrosinase Gene

Cited by 34 publications

References 14 publications

Delineating the genetic heterogeneity of OCA in Hungarian patients

Delineating the genetic heterogeneity of OCA in Hungarian patients

A Comprehensive Analysis Reveals Mutational Spectra and Common Alleles in Chinese Patients with Oculocutaneous Albinism

Una mirada al albinismo óculo-cutáneo: reporte de mutaciones en el gen TYR en cinco individuos colombianos

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