Hypopigmentation in the Prader-Willi syndrome correlates withP gene deletion but not with haplotype of the hemizygousP allele

Spritz, Richard A.; Bailin, Tu; Nicholls, Robert D.; Lee, Seung Taek; Park, Sang Kyw; Mascari, Maria J.; Butler, Merlin G.

doi:10.1002/(sici)1096-8628(19970711)71:1<57::aid-ajmg11>3.0.co;2-u

Cited by 89 publications

(75 citation statements)

References 22 publications

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“…Some of these clinical findings can now be interpreted in the light of our current knowledge of the molecular genetics of AS; patients with deletions have only a single copy of the P gene, a recessive gene known to cause Type II oculocutaneous albinism, and this is likely to be related to the hypopigmentation seen in this group (Spritz et al 1997). Typical AS deletion is of a large size, approximately 4 kb of DNA.…”

Section: Discussionmentioning

confidence: 98%

Angelman syndrome: evolution of the phenotype in adolescents and adults

Clayton‐Smith¹

2001

Develop Med Child Neuro

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Individuals with Angelman syndrome (AS) have severe learning disability, * at axia, seizures, dysmorphic facies, a happy, sociable disposition, and inability to speak. Most of the literature concerning the clinical features of AS has concentrated on younger children. This study aimed to look at the natural history of AS by documenting the clinical features in a group of 28 adolescents and adults with AS (12 males, 16 females; age range 16 to 40 years). Specific aspects studied included physical characteristics, general health, mobility, seizure disorder, behaviour and communication, and self‐help skills. Problems seen in this older group of individuals differed significantly from those typically observed in younger children. The incidence of scoliosis and joint contractures increased with age. Facial features were more striking in adults. Hyperactivity and concentration improved and the sociable disposition persisted. There were subtle clinical differences between the groups of individuals with different underlying genetic abnormalities. Information obtained from this study is relevant to diagnosis and management of older individuals with AS.

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Section: Discussionmentioning

confidence: 98%

Angelman syndrome: evolution of the phenotype in adolescents and adults

Clayton‐Smith¹

2001

Develop Med Child Neuro

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“…This is not surprising given the role of OCA2 in skin pigmentation. 26 Case 2 came to our attention only after his brain was donated to our brain bank, so we cannot comment on his skin pigmentation. The clinic notes we obtained have no mention of his pigmentation.…”

Section: Discussionmentioning

confidence: 99%

“…MS-MLPA reliably detected the deletion as evidenced by 100% agreement with our laboratory data and aCGH. It also provided more detailed information regarding the size of the deletion than standard FISH due to many (25)(26)(27)(28)(29)(30)(31)(32) probes across the 15q11.2-q13 region. Thus, the MS-MLPA technique allows for a reasonable approximation of the BPs and deletion size.…”

Section: Discussionmentioning

confidence: 99%

Unique and atypical deletions in Prader–Willi syndrome reveal distinct phenotypes

et al. 2011

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Prader-Willi syndrome (PWS) is a multisystem, contiguous gene disorder caused by an absence of paternally expressed genes within the 15q11.2-q13 region via one of the three main genetic mechanisms: deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect. The deletion class is typically subdivided into Type 1 and Type 2 based on their proximal breakpoints (BP1-BP3 and BP2-BP3, respectively). Despite PWS being a well-characterized genetic disorder the role of the specific genes contributing to various aspects of the phenotype are not well understood. Methylationspecific multiplex ligation-dependent probe amplification (MS-MLPA) is a recently developed technique that detects copy number changes and aberrant DNA methylation. In this study, we initially applied MS-MLPA to elucidate the deletion subtypes of 88 subjects. In our cohort, 32 had a Type 1 and 49 had a Type 2 deletion. The remaining seven subjects had unique or atypical deletions that were either smaller (n¼5) or larger (n¼2) than typically described and were further characterized by array-based comparative genome hybridization. In two subjects both the PWS region (15q11.2) and the newly described 15q13.3 microdeletion syndrome region were deleted. The subjects with a unique or an atypical deletion revealed distinct phenotypic features. In conclusion, unique or atypical deletions were found in B8% of the deletion subjects with PWS in our cohort. These novel deletions provide further insight into the potential role of several of the genes within the 15q11.2 and the 15q13.3 regions.

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“…Our findings about genotype-phenotype correlation in AS patients are in agreement with previous reports. All deletion cases had typical characteristics of AS including developmental delay, seizures and hypopigmentation (Spritz et al, 1997). We identified only one patient with pUPD with clinical features more moderate in comparison to patients with deletion.…”

Section: Discusionmentioning

confidence: 88%

Unusual Spectrum of Genetic Pathologies and Novel Mutations in PWS and as Patients Detected by a Wide Cluster of Methods

Kotysova¹,

Petrovič²,

Chandoga³

2014

OnLine Journal of Biological Sciences

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Prader-Willi and Angelman syndromes are clinically distinct neurodevelopmental genetic disorders that map to 15q11.2-q13 locus. The common phenotypes are attributable to loss of expression of parentally specific imprinted genes inside this region, where the gene function is dependent on parental origin. Initial diagnosis was proved for the years by methylation pattern analyses of the SNRPN exon 1/promoter region within the PWS/AS critical domain. Apart from unifying methylation-specific PCR and allele specific realtime PCR with melt-curve analysis as the fundamental methods for suspected diagnosis confirmation, we combined several specifically methods used to clarify the molecular cause. In our study we had identified and genotyped 24 PWS and AS patients from 450 suspected. Applied cluster of methods-microsatellite analysis of SNPs within the chromosome 15, Methylation-specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA) and UBE3A gene sequence analysis, enable us to determined atypical deletion that does not include common breakpoints, novel highly likely to be pathologic UBE3A mutation, uniparental heterodisomy together with partial isodisomy and epimutation without any deletions in the imprinting centre. We present genotype-phenotype correlation of all positive cases. In addition, we estimate the incidence for Slovakian population at 1 in 20,000 for PWS and 1 in 40,000 for AS.

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Hypopigmentation in the Prader-Willi syndrome correlates withP gene deletion but not with haplotype of the hemizygousP allele

Cited by 89 publications

References 22 publications

Angelman syndrome: evolution of the phenotype in adolescents and adults

Angelman syndrome: evolution of the phenotype in adolescents and adults

Unique and atypical deletions in Prader–Willi syndrome reveal distinct phenotypes

Unusual Spectrum of Genetic Pathologies and Novel Mutations in PWS and as Patients Detected by a Wide Cluster of Methods

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