Prader-Willi-like phenotype: investigation of 1p36 deletion in 41 patients with delayed psychomotor development, hypotonia, obesity and/or hyperphagia, learning disabilities and behavioral problems

D’Angelo, Carla Sustek; Paz, José Albino da; Kim, Chong; Bertola, Débora Romeo; Castro, Cláudia Irene Emílio de; Varela, Monica Castro; Koiffmann, Célia Priszkulnik

doi:10.1016/j.ejmg.2006.02.001

Cited by 48 publications

(59 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A Prader -Willi-like phenotype has been described in patients with chromosome Xq duplication, 11,12 fragile X, 13 monosomy 1p36, 14 and 6q deletion. 1 -7 Here we report five patients with interstitial 6q16 deletion defined by array-CGH analysis.…”

Section: Discussionmentioning

confidence: 99%

Detailed phenotype–genotype study in five patients with chromosome 6q16 deletion: narrowing the critical region for Prader–Willi-like phenotype

et al. 2008

View full text Add to dashboard Cite

Most patients with an interstitial deletion of 6q16 have Prader-Willi-like phenotype, featuring obesity, hypotonia, short hands and feet, and developmental delay. In all reported studies, the chromosome rearrangement was detected by karyotype analysis, which provides an overview of the entire genome but has limited resolution. Here we describe a detailed clinical presentation of five patients, two of whom were previously reported, with overlapping interstitial 6q16 deletions and Prader-Willi-like phenotype. Our patients share the following main features with previously reported cases: global developmental delay, hypotonia, obesity, hyperphagia, and eye/vision anomalies. All rearrangement breakpoints have been accurately defined through array-CGH at about 100 Kb resolution. We were able to narrow the shortest region of deletion overlap for the presumed gene(s) involved in the Prader -Willi-like syndrome to 4.1 Mb located at 6q16.1q16.2. Our results support the evidence that haploinsufficiency of the SIM1 gene is responsible for obesity in these patients. A possible involvement of the GRIK2 gene in autistic-like behaviour, of POPDC3 in heart development, and of MCHR2 in the control of feeding behaviour and energy metabolism is also hypothesized.

show abstract

Section: Discussionmentioning

confidence: 99%

Detailed phenotype–genotype study in five patients with chromosome 6q16 deletion: narrowing the critical region for Prader–Willi-like phenotype

et al. 2008

View full text Add to dashboard Cite

show abstract

“…A PWS-like phenotype, characterised by hypotonia, obesity, acromicria and variable motor, and cognitive delays, 3 has been reported in several conditions, such as maternal uniparental disomy for chromosome 14, 4,5 certain 1p36 deletions, 6,7 2p25 deletions, 8 Xq21 duplications, 9 Xq23q25 duplications, 10 and some cases of fragile X syndrome. 11,12 However, 6q16 deletion is the most common genetic abnormality in patients exhibiting the PWS-like phenotype.…”

Section: Introductionmentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1

et al. 2014

View full text Add to dashboard Cite

4,5,6 6q16 deletions have been described in patients with a Prader-Willi-like (PWS-like) phenotype. Recent studies have shown that certain rare single-minded 1 (SIM1) loss-of-function variants were associated with a high intra-familial risk for obesity with or without features of PWS-like syndrome. Although SIM1 seems to have a key role in the phenotype of patients carrying 6q16 deletions, some data support a contribution of other genes, such as GRIK2, to explain associated behavioural problems. We describe 15 new patients in whom de novo 6q16 deletions were characterised by comparative genomic hybridisation or single-nucleotide polymorphism (SNP) array analysis, including the first patient with fetopathological data. This fetus showed dysmorphic facial features, cerebellar and cerebral migration defects with neuronal heterotopias, and fusion of brain nuclei. The size of the deletion in the 14 living patients ranged from 1.73 to 7.84 Mb, and the fetus had the largest deletion (14 Mb). Genotype-phenotype correlations confirmed the major role for SIM1 haploinsufficiency in obesity and the PWS-like phenotype. Nevertheless, only 8 of 13 patients with SIM1 deletion exhibited obesity, in agreement with incomplete penetrance of SIM1 haploinsufficiency. This study in the largest series reported to date confirms that the PWS-like phenotype is strongly linked to 6q16.2q16.3 deletions and varies considerably in its clinical expression. The possible involvement of other genes in the 6q16.2q16.3-deletion phenotype is discussed.

show abstract

“…Among these, 17 scientific articles met the criteria for inclusion and were selected for this study (D'Angelo et al, 2006;Krepischi-Santos et al, 2006;Kang et al, 2007;Robinson et al, 2008;Bursztejn et al, 2009;El-Hattab et al, 2010;Gajecka et al, 2010;Rosenfeld et al, 2010;Haimi et al, 2011;Mikhail et al, 2011;Nicoulaz et al, 2011;Giannikou et al, 2012;Gervasini et al, 2013;Shiba et al, 2013;Zhu et al, 2013;Shimada et al, 2014;Stagi et al, 2014). Among these, 12 were case reports and five reported series of cases.…”

Section: Resultsmentioning

confidence: 99%

Mini-Review Monosomy 1p36 syndrome: reviewing the correlation between deletion sizes and phenotypes

et al. 2016

View full text Add to dashboard Cite

ABSTRACT. The major clinical features of monosomy 1p36 deletion are developmental delay and hypotonia associated with short stature and craniofacial dysmorphisms. The objective of this study was to review the cases of 1p36 deletion that was reported between 1999 and 2014, in order to identify a possible correlation between the size of the 1p36-deleted segment and the clinical phenotype of the disease. Scientific articles published in the (National Center for Biotechnology Information; NCBI http://www.ncbi.nlm. nih.gov/pubmed) and Scientific Electronic Library Online (www.scielo.com. br) databases were searched using key word combinations, such as "1p36 deletion", "monosomy 1p36 deletion", and "1p36 deletion syndrome". Articles in English or Spanish reporting the correlation between deletion sizes and the respective clinical phenotypes were retrieved, while letters, reviews, guidelines, and studies with mouse models were excluded. Among the 746 retrieved articles, only 17 (12 case reports and 5 series of cases), comprising 29 patients (9 males and 20 females, aged 0 months (neonate) to 22 years) bearing the 1p36 deletions and whose clinical phenotypes were described, met the inclusion criteria. The genotype-phenotype correlation in monosomy 1p36 is a challenge because of the variability in the size of the deleted segment, as well as in the clinical manifestations of similar size deletions. Therefore, the severity of the clinical features was not always associated with the deletion size, possibly because of the other influences, such as stochastic factors, epigenetic events, or reduced penetration of the deleted genes.

show abstract

Prader-Willi-like phenotype: investigation of 1p36 deletion in 41 patients with delayed psychomotor development, hypotonia, obesity and/or hyperphagia, learning disabilities and behavioral problems

Cited by 48 publications

References 19 publications

Detailed phenotype–genotype study in five patients with chromosome 6q16 deletion: narrowing the critical region for Prader–Willi-like phenotype

Detailed phenotype–genotype study in five patients with chromosome 6q16 deletion: narrowing the critical region for Prader–Willi-like phenotype

Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1

Mini-Review Monosomy 1p36 syndrome: reviewing the correlation between deletion sizes and phenotypes

Contact Info

Product

Resources

About