Delineating the genetic heterogeneity of OCA in Hungarian patients

Fábos, Beáta; Farkas, Katalin; Tóth, László; Sulák, Adrienn; Tripolszki, Kornélia; Tihanyi, Mariann; Németh, Réka; Vas, Krisztina; Csoma, Zsanett; Kemény, Lajos; Széll, Márta; Nagy, Nikoletta

doi:10.1186/s40001-017-0262-0

Cited by 7 publications

(5 citation statements)

References 33 publications

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“…In India, the prevalence rates of OCA1 and OCA2 are 59.8% and 10.9%, respectively [ 13 ]. OCA1 (69%) and OCA4 (23%) are the most frequent forms in Hungary [ 14 ]. OCA1 is the most common variant in Caucasians [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

NGS-based targeted sequencing identified two novel variants in Southwestern Chinese families with oculocutaneous albinism

et al. 2022

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Background Oculocutaneous albinism (OCA) is a group of heterogeneous genetic diseases characterized by a reduction or complete lack of pigmentation in the hair, skin, and eyes. It is associated with reduced visual acuity, nystagmus, photophobia, and strabismus. OCA type 1 (OCA1) and type 2 (OCA2) are caused by mutations in the tyrosinase (TYR) and OCA2 genes, which are responsible for most cases of OCA. The present study aimed to identify the mutational spectra of 18 southwest Chinese probands with OCA. Results We used a skin disease-targeted panel to sequence more than 400 genes, including 23 genes (TYR, OCA2, AP3B1, BLOC1S3, BLOC1S6, C10orf11, DTNBP1, FRMD7, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, LYST, MC1R, MITF, MLPH, MYO5A, RAB27A, SLC24A5, SLC45A2, TYRP1) associated with syndromic and non-syndromic albinism. The targeted panel was applied to 18 patients from southwest China, nine (50%) patients were diagnosed with OCA1, and nine (50%) were diagnosed with OCA2. Our data indicate that OCA1 and OCA2, the most common subtypes, probably have the same prevalence in southwest China. In total, we identified 26 variants in TYR and OCA2 from 18 OCA cases using the NGS technology, including 24 variants presented in the Human Gene Mutation Database Professional (HGMD) and two novel variants, c.559_560insCATTATTATGTGTCAAATTATCCCC in TYR and c.1514 T > C in OCA2, which have not been previously reported. According to the American College of Medical Genetics and Genomics (ACMG) classification, c.559_560insCATTATTATGTGTCAAATTATCCCC (p.G190Cfs*12) is classified as a pathogenic variant, and c.1514 T > C (p.F505S) is evaluated as a likely pathogenic variant. Conclusions Two novel variants were identified which will expand the mutational spectra of TYR and OCA2. The results of the present study may have implications for genetic counseling, carrier screening, and clinical management of the disease.

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Section: Discussionmentioning

confidence: 99%

NGS-based targeted sequencing identified two novel variants in Southwestern Chinese families with oculocutaneous albinism

et al. 2022

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“…Oculocutaneous albinism (OCA) is a group of rare autosomal recessive disorders with clinical genetic heterogeneity. It is characterized by reduced pigment in the eyes, skin, and hair due to the deficiency in melanin synthesis, leading to ocular abnormalities such as poor vision, nystagmus, and an increased risk of light damage and skin cancer (Fábos et al., 2017). The prevalence of OCA is about 1/17,000 globally and 1/18,000 among the Chinese Han population (Grønskov et al., 2007; Wang et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

Novel compound heterozygous mutations in OCA2 gene were identified in a Chinese family with oculocutaneous albinism

Jiang,

Zhang,

Kan

et al. 2023

Molec Gen & Gen Med

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BackgroundOculocutaneous albinism (OCA) is a group of rare autosomal recessive disorders characterized by clinical genetic heterogeneity. OCA type II (OMIM: 203200) is the most common subtype among African and African Americans, primarily caused by pathogenic variants in the OCA2 (HGNC ID: 8101) gene. In this study, we presented a Chinese family with OCA and reported two novel variants in the OCA2 gene.MethodsWhole‐exome sequencing (WES) was performed to identify pathogenic variants in the proband. The candidate variants were subsequently validated using Sanger sequencing and QPCR assay. Additionally, bioinformatics analyses were employed to predict the deleteriousness and conservation of the identified mutations.ResultsIn the 16‐year‐old male proband, two novel compound heterozygous OCA2 variants, NM_000275.3: c.1640T>G (NP_000266.2: p.L547R) and an exons 10‐19 deletion variant, were identified. Meanwhile, a reported heterozygous variant c.1441G>A/p.A481T (NM_000275.3, NP_000266.2) in the OCA2 gene was also found in the proband. Sanger sequencing confirmed that the two variants c.1441G>A/p.A481T and c.1640T>G/p.L547R were inherited from his father. Moreover, qPCR assay revealed that the exons 10‐19 deletion was inherited from the mother, his sister also carried this variant. Fortunately, the variant was not detected in the amniotic fluid of the proband's sister. Multiple online bioinformatics tools predicted the variant c.1640T>G to be damaging, leading to the replacement of a highly conserved leucine with an arginine. The gross exon 10‐19 deletion in the OCA2 gene resulted in a truncated, non‐functional protein losing the 3–9 transmembrane α‐helices domains. According to the American College of Medical Genetics and Genomics classification, these three variants in the OCA2 gene were evaluated as likely pathogenic.ConclusionThis study has identified two novel compound variants in the OCA2 gene and a previously reported variant in a Chinese family with OCA. By expanding the mutation spectrum of the OCA2 gene, our findings contribute to a better understanding of the genetic basis of OCA.

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Section: Discussionmentioning

confidence: 70%

“…In five patients, two different heterozygous pathogenic mutations were present, whereas seven patients had only one pathogenic mutation and associated non-pathogenic variants (Fábos et al, 2017). Therefore, my results suggest that the concomitant screening of the non-pathogenic variantswhich alone do not cause 35 the development of OCA, but might have clinical significance in association with a pathogenic variant -is important (Fábos et al, 2017).…”

Section: Discussionmentioning

confidence: 74%

“…Besides the identification of novel mutations, the other significant results of my study are the followings: Although, the clinical features of the investigated Hungarian OCA patients (n=12) were identical, the molecular genetic data suggested an OCA1 subtype in nine cases and an OCA4 subtype in three cases (Fábos et al, 2017). In five patients, two different heterozygous pathogenic mutations were present, whereas seven patients had only one pathogenic mutation and associated non-pathogenic variants (Fábos et al, 2017). Therefore, my results suggest that the concomitant screening of the non-pathogenic variantswhich alone do not cause 35 the development of OCA, but might have clinical significance in association with a pathogenic variant -is important (Fábos et al, 2017).…”

Section: Discussionmentioning

confidence: 74%

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Genetic and environmental risk factors, informative subtypes and putative endophenotypes in major depressive disorder

Fábos

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Background: Oculocutaneous 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). Methods: The 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. Results: Although 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. Conclusions: Our 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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Delineating the genetic heterogeneity of OCA in Hungarian patients

Cited by 7 publications

References 33 publications

NGS-based targeted sequencing identified two novel variants in Southwestern Chinese families with oculocutaneous albinism

NGS-based targeted sequencing identified two novel variants in Southwestern Chinese families with oculocutaneous albinism

Novel compound heterozygous mutations in OCA2 gene were identified in a Chinese family with oculocutaneous albinism

Genetic and environmental risk factors, informative subtypes and putative endophenotypes in major depressive disorder

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