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Cited by 298Genetic Syndromes and ImprintingGenomic variations and chromosomal abnormalitiesWilliams Syndrome Research

Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy

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Butler, Merlin G., Bittel, Douglas C., Kibiryeva, Nataliya, Talebizadeh, Zohreh, Thompson, Travis·2004·Pediatrics
DOI 10.1542/peds.113.3.565PMC PMC6743499
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Abstract

OBJECTIVE: To determine whether phenotypic differences exist among individuals with Prader-Willi syndrome with either type I or type II deletions of chromosome 15 or maternal disomy 15 leading to a better understanding of cause and pathophysiology of this classical genetic syndrome. METHODS: We analyzed clinical, anthropometric, and behavioral data in 12 individuals (5 men, 7 women; mean age: 25.9 +/- 8.8 years) with PWS and a type I (TI) deletion, 14 individuals (6 men, 8 women; mean age: 19.6 +/- 6.5 years) with PWS and a type II (TII) deletion, and 21 individuals (10 men, 11 women; mean age: 23.6 +/- 9.2 years) with PWS and maternal disomy 15 (UPD). The deletion type was determined by genotyping of DNA markers between proximal chromosome 15 breakpoints BP1 and BP2. TI deletions are approximately 500 kb larger than TII deletions. Several validated psychological and behavioral tests were used to assess phenotypic characteristics of individuals with PWS representing the 3 genetic subtypes. RESULTS: Significant differences were found between the 2 deletion groups and those with UPD in multiple psychological and behavioral tests, but no differences were observed in other clinical or anthropometric data studied. Adaptive behavior scores were generally worse in individuals with PWS and the TI deletion, and specific obsessive-compulsive behaviors were more evident in the TI individuals compared with those with UPD. Individuals with PWS with TI deletions also had poorer reading and math skills as well as visual-motor integration. CONCLUSIONS: Our study indicates that individuals with TI deletion generally have more behavioral and psychological problems than individuals with the TII deletion or UPD. Four recently identified genes have been identified in the chromosome region between BP1 and BP2 with 1 of the genes (NIPA-1) expressed in mouse brain tissue but not thought to be imprinted. It may be important for brain development or function. These genes are deleted in individuals with TI deletion and are implicated in compulsive behavior and lower intellectual ability in individuals with TI versus TII.

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  • PWS individuals with type I deletions showed more compulsive and self-injurious behaviors and visual perception impairment along with lower intelligence, reading and math scores than those with type II deletions.

    “PWS individuals with type I deletions showed more compulsive and self-injurious behaviors and visual perception impairment along with lower intelligence, reading and math scores than in those with type II deletions.”

    From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [5]

    The Discussion (page unavailable) reports more compulsive behavior and poorer visual perception with type I than type II deletions. The Results and Abstract also support poorer reading and math performance and lower intellectual ability. But the Discussion explicitly says those with type I deletions did not display more self-injury than those with type II deletions. (LLM, conf=0.91)

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  • Individuals with the larger typical 15q11-q13 type I deletion in Prader-Willi and Angelman syndromes have more severe neurodevelopmental symptoms than those with the smaller typical type II deletion.

    “Several studies have shown that individuals with the larger typical 15q11–q13 type I deletion which is found in both Prader-Willi and Angelman syndromes are reported to have more severe neurodevelopmental symptoms as compared to those individuals with the smaller typical type II deletion [5,6,7,8,9,10].”

    From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [5]

    The Abstract reports that type I deletions are larger than type II deletions and that people with Prader-Willi syndrome and type I deletions generally had more behavioral and psychological problems. The study did not compare deletion types in Angelman syndrome, and the Discussion cautions that most measured characteristics did not differ significantly between deletion groups. It therefore supports the Prader-Willi portion, not the claim across both syndromes. (LLM, conf=0.88)

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References 32 · Cited by 298

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Authors
Butler, M. G., Bittel, D. C., Kibiryeva, N., Talebizadeh, Z., & Thompson, T.
Affiliations
  • Children's Mercy Hospital (US)
  • University of Kansas Medical Center (US)
ORCID
Venue
Pediatrics
Publisher
American Academy of Pediatrics (AAP)
Published
2004-03-01
Volume
113
Issue
3
Pages
565-573
ISSN
  • 0031-4005 (ISSN-L)
  • 1098-4275
DOI
10.1542/peds.113.3.565
PMC
PMC6743499
OpenAlex
W2094215765
Cited by
298
References
32
Citations by year
2026: 6 · 2025: 10 · 2024: 10 · 2023: 12 · 2022: 20 · 2021: 13 · 2020: 14 · 2019: 15 · 2018: 10 · 2017: 6 · 2016: 17 · 2015: 13 · 2014: 10 · 2013: 9 · 2012: 11
FWCI
9.10
Type
journal article
Language
en
Open access
Locations
  • PEDIATRICS (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Child Health and Human Development
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD 30329, R01 HD41672, P01HD030329, R01HD041672)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
Keywords
Prader-Willi syndrome, chromosome 15q11-q13 deletion, uniparental disomy, behavioral phenotypes, obsessive-compulsive behavior, adaptive behavior, intellectual disability, visual-motor integration, genomic imprinting, brain development
MeSH terms
Adult, Mental Disorders, Chromosome Deletion, Chromosomes, Human, Pair 15, Female, Humans, Male, Phenotype, Prader-Willi Syndrome, Uniparental Disomy

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