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

Akahoshi, Keiko; Spritz, Richard A.; Fukai, Kazuyoshi; Mitsui, Norimasa; Matsushima, Kazushige; Ohashi, Hirofumi

doi:10.1002/ajmg.a.20580

Cited by 15 publications

(12 citation statements)

References 9 publications

(10 reference statements)

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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: 50%

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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confidence: 50%

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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“…Patients with a proximal 15q trisomy or hexasomy display a hyperpigmentation phenotype underscoring the view that skin pigmentation is correlated with OCA2 gene copy number (Akahoshi et al., ; Kraoua et al., ). Furthermore, it was demonstrated that a patient who exhibited pigmentary dysplasia of the skin – with normal pigmented areas surrounded by larger, hyperpigmented areas – was mosaic for a duplication of the proximal part of 15q‐ and accordingly had quadruple FISH signals for the OCA2 gene (Akahoshi et al., ).…”

Section: Oca2 Transcription Levels and Pigmentationmentioning

confidence: 99%

Genetic variation in regulatory DNA elements: the case of OCA2 transcriptional regulation

Visser

Kayser

Grosveld

et al. 2014

Pigment Cell Melanoma Res

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Summary Mutations within the OCA2 gene or the complete absence of the OCA2 protein leads to oculocutaneous albinism type 2. The OCA2 protein plays a central role in melanosome biogenesis, and it is a strong determinant of the eumelanin content in melanocytes. Transcript levels of the OCA2 gene are strongly correlated with pigmentation intensities. Recent studies demonstrated that the transcriptional level of OCA2 is to a large extent determined by the noncoding SNP rs12913832 located 21.5 kb upstream of the OCA2 gene promoter. In this review, we discuss current hypotheses and the available data on the mechanism of OCA2 transcriptional regulation and how this is influenced by genetic variation. Finally, we will explore how future epigenetic studies can be used to advance our insight into the functional biology that connects genetic variation to human pigmentation.

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“…It typically includes hypotonia, motor, and speech delay, seizures, moderate to severe learning disability and autism. Less welldocumented features include hyperpigmentation, which may be related to additional copies of the OCA2 gene [Akahoshi et al, 2001[Akahoshi et al, , 2004 and abnormalities of pubertal development in females [Grosso et al, 2001]. Growth is usually normal, major malformations are rare, and dysmorphic features are absent or subtle; hence, chromosome analysis may not be thought to be indicated, and many, particularly in the older age groups, probably remain undiagnosed.…”

Section: Introductionmentioning

confidence: 99%

Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11‐q13

Dennis

Veltman

Thompson

et al. 2006

American J of Med Genetics Pt A

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We present clinical data on 33 subjects with additional copies of the Prader-Willi-Angelman critical region (PWACR) contained in a supernumerary marker chromosome (SMC). Twenty-three subjects had a typical large non-mosaic SMC(15) containing two copies of the PWACR. They showed a variable but generally severe phenotype of learning disability and autism, with seizures in approximately two-thirds. The other 10 differed from this typical pattern in respect of mosaicism, variation in copy number, or arrangement of the PWACR within the SMC or number of SMC per cell. Clinical severity increased with the number of additional copies of the PWACR and decreased with mosaicism for a normal cell line. There was a trend for a larger number of seizures to be associated with more severe learning disability. Three subjects with interstitial triplications of 15q11-q13 showed a range of phenotypes similar to those of the typical large SMC(15). All additional copies of the PWACR in this series were maternally-derived. FISH and molecular data localizing the breakpoints of the rearrangements have been previously published or are included in this report. No correlations were found between specific clinical features and variations in breakpoints proximal and distal to the PWACR.

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

Cited by 15 publications

References 9 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

Genetic variation in regulatory DNA elements: the case of OCA2 transcriptional regulation

Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11‐q13

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