Duplication of 15q11.2-q14, including theP gene, in a woman with generalized skin hyperpigmentation

Akahoshi, Keiko; Fukai, Kazuyoshi; Kato, Atsushi; Kimiya, Satoshi; Kubota, Takeo; Spritz, Richard A.

doi:10.1002/ajmg.10095

Cited by 22 publications

(16 citation statements)

References 15 publications

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“…However, these hypopigmentations are not observed in the cases of UPD because both OCA2 alleles are expressed. Conversely, duplication of 15q11.2q14 causes hyperpigmentation [Akahoshi et al, 2001] and mosaic supplementary inv dup (15) causes pigmentary dysplasia [Akahoshi et al, 2004]. These reports clearly show the gene dosage effect of OCA2 .…”

supporting

confidence: 49%

Angelman Syndrome Caused by Chromosomal Rearrangements: A Case Report of 46,XX,+der(13)t(13;15)(q14.1;q12)mat,-15 with an Atypical Phenotype and Review of the Literature

Niida

Sato²,

Ozaki³

et al. 2016

Cytogenet Genome Res

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Less than 1% of the cases with Angelman syndrome (AS) are caused by chromosomal rearrangements. This category of AS is not well defined and may manifest atypical phenotypes. Here, we report a girl with AS due to der(13)t(13;15)(q14.1;q12)mat. SNP array detected the precise deletion/duplication points and the parental origin of the 15q deletion. Multicolor FISH confirmed a balanced translocation t(13;15)(q14.1;q12) in her mother. Her facial appearance showed some features of dup(13)(pter→q14). Also, she lacked the most characteristic and unique behavioral symptoms of AS, i.e., frequent laughter, happy demeanor, and easy excitability. A review of the literature indicated that AS cases caused by chromosomal rearrangements can be classified into 2 major categories and 4 groups. The first category is paternal uniparental disomy 15, which is subdivided into isodisomy by de novo rob(15;15) and heterodisomy caused by paternal translocation. The second category is the deletion of the AS locus due to maternal reciprocal translocation, which is subdivided into 2 groups associated with partial monosomy by 3:1 segregation and partial trisomy by adjacent-2 segregation. Classification into these categories facilitates the understanding of the mechanisms of chromosomal rearrangements and helps in accurate diagnosis and genetic counseling of these rare forms of AS.

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supporting

confidence: 49%

Angelman Syndrome Caused by Chromosomal Rearrangements: A Case Report of 46,XX,+der(13)t(13;15)(q14.1;q12)mat,-15 with an Atypical Phenotype and Review of the Literature

Niida

Sato²,

Ozaki³

et al. 2016

Cytogenet Genome Res

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“…The skin patterns may reflect different copy numbers of the P gene in his two cell lines, i.e., six copies in cells with an extra inv dup(15) chromosome versus two copies in those with a normal karyotype. This hypothesis is potentially supported by our previous finding in a woman with generalized hyperpigmentation associated with a 15q11.2-q14 duplication, including a duplication of the P gene [Akahoshi et al, 2001]. PWS or AS patients hemizygous for the P gene are usually hypopigmented, regardless of the composition of their intact P allele [Spritz et al, 1997].…”

Section: Discussionmentioning

confidence: 73%

Mosaic supernumerary inv dup(15) chromosome with four copies of the P gene in a boy with pigmentary dysplasia

Akahoshi

Spritz

Fukai

et al. 2003

American J of Med Genetics Pt A

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Association of the pink-eye-dilution gene (P) with hypopigmentation is seen in patients who have oculocutaneous albinism type 2 (OCA2) and Prader-Willi syndrome (PWS) or Angelman syndrome (AS). However, it remains unknown whether duplication or amplification of the P gene causes hyperpigmentation. We previously reported a woman who had hyperpigmentation with a duplication of the proximal part of 15q, including the P gene. Here, we describe an additional patient with mosaicism of inv dup(15) and clinical manifestations of severe psychmoter retardation, epilepsy, and pigmentary dysplasia showing mottled and linear patterns of hyperpigmentation. His karyotype was 47,XY,+idic(15)(pter-->q14::q14-->pter)[38]/46,XY[12] de novo. Chromosomal fluorescence in situ hybridization (FISH) showed six copies of the P gene. Therefore, his cutaneous mosaicism might be caused by the presence of both normal and hyperpigmented skin due to multicopies of the P gene.

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“…A duplication of the whole OCA2 gene was previously described (Akahoshi et al 2001), leading to hyperpigmentation due to overexpression of the OCA2 protein. In contrast, the intragenic duplication described here supposedly disrupts the gene and leads to a loss of function, hence resulting in the albino phenotype.…”

Section: Discussionmentioning

confidence: 96%

High resolution mapping of OCA2 intragenic rearrangements and identification of a founder effect associated with a deletion in Polish albino patients

et al. 2010

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Oculocutaneous albinism type 2 (OCA2) represents about 30% of OCA worldwide. Using quantitative multiplex fluorescent PCR and very high-resolution array-CGH focussed on the OCA2 gene and surrounding regions in 15q12, we identified new rearrangements. Deletion 1, encompassing exons 3-20, was present in three patients (including one in the homozygous state), and Deletion 2 (exons 1-20) was found in one patient (heterozygous state). The duplication (exons 3-20) was found in one patient in the homozygous state. Using 14 microsatellite markers we determined haplotypes associated with these rearrangements. Deletion 1 was associated with the same haplotype in three patients who were all of Polish origin, which is strongly in favour of a founder effect. Deletion 2 was associated with a distinct haplotype. The homozygous duplication was inherited from the two unrelated parents of the patients on two different haplotypes. Analysis of the sequences around the breakpoints of these rearrangements showed that all occurred within complex arrays of repetitive sequences. The combined use of very high-resolution array-CGH and of microsatellites (including new intragenic ones described here) constitutes a powerful approach for the precise characterization of OCA2 rearrangements, which have been found in more than 20% of OCA2 patients.

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Duplication of 15q11.2-q14, including theP gene, in a woman with generalized skin hyperpigmentation

Cited by 22 publications

References 15 publications

Angelman Syndrome Caused by Chromosomal Rearrangements: A Case Report of 46,XX,+der(13)t(13;15)(q14.1;q12)mat,-15 with an Atypical Phenotype and Review of the Literature

Angelman Syndrome Caused by Chromosomal Rearrangements: A Case Report of 46,XX,+der(13)t(13;15)(q14.1;q12)mat,-15 with an Atypical Phenotype and Review of the Literature

Mosaic supernumerary inv dup(15) chromosome with four copies of the P gene in a boy with pigmentary dysplasia

High resolution mapping of OCA2 intragenic rearrangements and identification of a founder effect associated with a deletion in Polish albino patients

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