Oculocutaneous albinism (OCA) in Japanese patients: Five novel mutations

Okamura, Ken; Yoshizawa, Junko; Abe, Yuko; Hanaoka, Keiko; Higashi, Naoyuki; Togawa, Yaei; Nakagawa, Satoko; Kambe, Naotomo; Funasaka, Yoko; Ohko, Kentaro; Hozumi, Yasukazu; Suzuki, Tamio

doi:10.1016/j.jdermsci.2013.12.011

Cited by 13 publications

(11 citation statements)

References 8 publications

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“…Albinism is a group of rare genetic disorders, characterized by a reduction or deficiency of melanin in melanocyte‐containing organs such as skin, hair, and eyes (Okamura et al, ). To date, 22 potential causative genes (19 genes summarized by Montoliu and Marks (Montoliu & Marks, ), and three causative genes for Griscelli syndrome) for albinism have been identified.…”

Section: Mutation and Phenotype Analysis For Patients With Albinismmentioning

confidence: 99%

“…In addition, approximately 10% of Japanese patients with albinism are diagnosed with the HPS1 subtype. Of note, there have only been a few case reports describing the occurrence of other subtypes of albinism, including OCA3, HPS4, HPS6, and HPS9 among Japanese individuals (Araki et al, ; Miyamichi et al, ; Okamura et al, , ; Yamada et al, ). Until 2016, mutational screening for the causal genes of the most frequent albinism subtypes (OCA1‐4 and HPS1) in the Japanese population was performed using SSCP analysis (Inagaki et al, ).…”

Section: Mutation and Phenotype Analysis For Patients With Albinismmentioning

confidence: 99%

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NGS‐based targeted resequencing identified rare subtypes of albinism: Providing accurate molecular diagnosis for Japanese patients with albinism

Okamura

Hayashi

Abe

et al. 2019

Pigment Cell Melanoma Res

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Albinism, which is commonly inherited as an autosomal recessive trait, is characterized by a reduction or absence of melanin in the eyes, skin, and hair. To date, more than 20 causal genes for albinism have been identified; thus, the accurate diagnosis of albinism requires next‐generation sequencing (NGS). In this study, we analyzed 46 patients who tested negative for oculocutaneous albinism (OCA)1–4 and Hermansky‐Pudlak syndrome (HPS)1 based on conventional analysis, in addition to 28 new Japanese patients, using NGS‐based targeted resequencing. We identified a genetic background for albinism in 18 of the 46 patients (39%), who were previously tested negative according to the conventional analysis. In addition, we unveiled a genetic predisposition toward albinism in 23 of the 28 new patients (82%). We identified six patients with rare subtypes of albinism, including HPS3, HPS4, and HPS6, and found 12 novel pathological mutations in albinism‐related genes. Furthermore, most patients who were not diagnosed with albinism by the NGS analysis showed mild manifestations of albinism without apparent eye symptoms and harbored only one heterozygous mutation, occasionally in combination with skin‐color associated gene variants.

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Section: Mutation and Phenotype Analysis For Patients With Albinismmentioning

confidence: 99%

Section: Mutation and Phenotype Analysis For Patients With Albinismmentioning

confidence: 99%

NGS‐based targeted resequencing identified rare subtypes of albinism: Providing accurate molecular diagnosis for Japanese patients with albinism

Okamura

Hayashi

Abe

et al. 2019

Pigment Cell Melanoma Res

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“…Oculocutaneous albinism (OCA) represents a group of autosomal recessive disorders characterized by a reduction or deficiency of melanin in the eyes, skin, and hair. OCA is broadly classified into two groups: nonsyndromic and syndromic, based on the presence of additional symptoms, such as bleeding diathesis, immunodeficiency, or neurological dysfunction (Okamura et al., ). OCA type 4 (OCA4; OMIM 611409) is a nonsyndromic type of OCA, caused by mutations in SLC45A2 (Newton et al., ).…”

Section: Genotype–phenotype Relationship In Oca4‐suspected Patientsmentioning

confidence: 99%

“…Clinically, p.G89R and p.S90CfsX22 are also supposed to have no activity in melanogenesis, while p.F219del, p.T440A, and p.V507L are considered to have some remaining activity (Inagaki et al., , ; Rundshagen, Zuhlke, Opitz, Schwinger, & Kasmann‐Kellner, ), suggesting that the c.‐492_489delAATG variant could cause OCA4 in combination with not only the null alleles but also the alleles with some remaining activity. In contrast to OCA4 patients with no activity of SLC45A2 (e.g., patients with homozygous p.D157N), most of them show severe eye manifestation including nystagmus, amblyopia, and photophobia (Inagaki et al., ; Okamura et al., , ), their phenotype was characterized by mildness of symptoms, especially the manifestation of the disease in the eyes was mild, which primarily affects the quality of their lives. This phenotype resembles the phenotype of the medaka ( b ), traditionally called the orange–red variant, which is characterized by amelanotic skin but melanized eyes (Aida, ; Fukamachi et al., ; Shimada, Fukamachi, Wakamatsu, Ozato, & Shima, ).…”

Section: Genotype–phenotype Relationship In Oca4‐suspected Patientsmentioning

confidence: 99%

A 4‐bp deletion promoter variant (rs984225803) is associated with mild OCA4 among Japanese patients

Okamura

Hayashi

Nakajima

et al. 2018

Pigment Cell Melanoma Res

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Oculocutaneous albinism (OCA) type 4 is one of the most common types of albinism among Japanese population. In some patients who were clinically diagnosed with OCA, we have found a heterozygous pathological mutation in the coding region of SLC45A2, the gene responsible for OCA4, not leading to a DNA-based diagnosis. In this study, we evaluated pathological variants in the promoter region of SLC45A2 in these patients. The results indicated that the majority of the patients had a 4-bp deletion in the said region (c.-492_489delAATG; GenBank accession number: NM_016180; rs984225803) in the contralateral allele. These patients displayed a mild phenotype, especially regarding eye manifestations. The results of the luciferase reporter assay and electrophoretic mobility shift assay supported the pathological role of the variant. In addition, four of 220 alleles in Japanese normal control subjects also showed the deletion variant, indicating that this variant could possibly be a skin color-associated variant.

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“…The EDA gene encodes ectodysplasin-A, a protein that belongs to the tumor necrosis factor ligand superfamily. 1 A 6-year-old Japanese boy presented with recurrent episodes of high body temperature during the summer. He had manifested xerosis and dermatitis shortly after birth, and he was treated based on a diagnosis of atopic dermatitis.…”

Section: Acknowledgmentsmentioning

confidence: 99%