Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region

Berg, Jonathan S.; Brunetti‐Pierri, Nicola; Peters, Sarika U.; Kang, Sung Hae L.; Fong, Chin To; Salamone, Jessica; Freedenberg, Debra; Hannig, Vickie; Prock, Lisa Albers; Miller, David T.; Raffalli, Peter; Harris, David J.; Erickson, Robert P.; Cunniff, Christopher; Clark, Gary D.; Blazo, Maria; Peiffer, Daniel A.; Gunderson, Kevin L.; Sahoo, Trilochan; Patel, Ankita; Lupski, James R.; Beaudet, Arthur L.; Cheung, Sau Wai

doi:10.1097/gim.0b013e3180986192

Cited by 174 publications

(178 citation statements)

References 59 publications

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…Using FISH and quantitative real time PCR, the size of the duplication was calculated generally to be the same size as of the common deletion region in WBS (~1.5 Mb). The breakpoints occur within the LCR blocks B cen and B mid with an increased expression of the genes within the single copy region of WBS [110,111]. Smaller and larger duplication sizes have also been reported [111,117,118].…”

mentioning

confidence: 92%

“…The breakpoints occur within the LCR blocks B cen and B mid with an increased expression of the genes within the single copy region of WBS [110,111]. Smaller and larger duplication sizes have also been reported [111,117,118]. Duplications within the WBS region are supposed to result from the same mechanism of unequal meiotic recombination as the occurrence of deletions in this region.…”

mentioning

confidence: 96%

“…In a third of cases, the duplication is inherited from one parent; in a few of the reported families, the chromosome-transmitting parent displayed a mild pattern of WBS-duplication typical symptoms. This observation of only minor symptoms in the duplication-carrying parent could imply that, in addition to gene dosage effects, other mechanisms such as genetic and/or environmental interactions are important in determining the phenotypic outcome of patients with this genetic aberration [109,111,116,118]. Using FISH and quantitative real time PCR, the size of the duplication was calculated generally to be the same size as of the common deletion region in WBS (~1.5 Mb).…”

mentioning

confidence: 99%

See 2 more Smart Citations

The genomic basis of the Williams – Beuren syndrome

Schubert

2008

Cell. Mol. Life Sci.

214

161

View full text Add to dashboard Cite

. The Williams-Beuren syndrome is a genomic disorder (prevalence: 1/7,500 to 1/20,000), caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Typical symptoms comprise supravalvular aortic stenosis, mental retardation, overfriendliness and visuospatial impairment. The common deletion sizes range of 1.5–1.8 mega base pairs (Mb), encompassing app. 28 genes. For a few genes, a genotype-phenotype correlation has been established. The best-explored gene within this region is the elastin gene; its haploinsufficiency causes arterial stenosis. The region of the Williams-Beuren syndrome consists of a single copy gene region (~1.2 Mb) flanked by repetitive sequences – Low Copy Repeats (LCR). The deletions arise as a consequence of misalignment of these repetitive sequences during meiosis and a following unequal crossing over due to high similarity of LCRs. This review presents an overview of the Williams-Beuren syndrome region considering the genomic assembly, chromosomal rearrangements and their mechanisms (i.e. deletions, duplications, inversions) and evolutionary and historical aspects.

show abstract

mentioning

confidence: 92%

mentioning

confidence: 96%

mentioning

confidence: 99%

See 1 more Smart Citation

The genomic basis of the Williams – Beuren syndrome

Schubert

2008

Cell. Mol. Life Sci.

214

161

View full text Add to dashboard Cite

show abstract

“…15 For many of the recurrent microdeletion syndromes caused by NAHR, reciprocal microduplications have been identified and 16 has a reciprocal microduplication that is also characterized by variable phenotypes (OMIM 611936). 17 Two more well-characterized examples are Williams syndrome (OMIM 194050), due to a microdeletion at 7q11.23, and its reciprocal microduplication syndrome (OMIM 609757); 18,19 and Smith-Magenis syndrome (OMIM 182290), due to microdeletion at 17p11.2, and Potocki-Lupski syndrome (OMIM 610883), caused by the reciprocal microduplication. 20,21 Analysis of the phenotypic consequences of the reciprocal NF1 microduplications, however, has been reported in detail in just one multigenerational family.…”

Section: Introductionmentioning

confidence: 99%

NF1 microduplications: identification of seven nonrelated individuals provides further characterization of the phenotype

Moles

Gowans

Gedela

et al. 2012

Genetics in Medicine

View full text Add to dashboard Cite

Purpose: Neurofibromatosis, type 1 (NF1) is an autosomal dominant disorder caused by mutations of the neurofibromin 1 (NF1) gene at 17q11.2. Approximately 5% of individuals with NF1 have a 1.4-Mb heterozygous 17q11.2 deletion encompassing NF1, formed through nonallelic homologous recombination (NAHR) between the low-copy repeats that flank this region. NF1 microdeletion syndrome is more severe than NF1 caused by gene mutations, with individuals exhibiting facial dysmorphisms, developmental delay (DD), intellectual disability (ID), and excessive neurofibromas. Although NAHR can also cause reciprocal microduplications, reciprocal NF1 duplications have been previously reported in just one multigenerational family and a second unrelated proband. methods:We analyzed the clinical features in seven individuals with NF1 microduplications, identified among 48,817 probands tested in our laboratory by array-based comparative genomic hybridization. Results:The only clinical features present in more than one individual were variable DD/ID, facial dysmorphisms, and seizures. No neurofibromas were present. Three sets of parents were tested: one duplication was apparently de novo, one inherited from an affected mother, and one inherited from a clinically normal father.conclusion: This is the first report comparing the phenotypes of nonrelated individuals with NF1 microduplications. This comparison will allow for further definition of this emerging microduplication syndrome.Genet Med 2012:14(5):508-514

show abstract

“…Individuals with 7q11.23 duplications exhibit a highly heterogeneous phenotype. Common features include ASD, cognitive deficits, severe expressive language delay, facial dysmorphisms (e.g., short philtrum and thin lips), anxiety, behavioral problems, and hyperactivity [98,116,117].…”

Section: Q1123mentioning

confidence: 99%

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms

et al. 2015

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a group of highly genetic neurodevelopmental disorders characterized by language, social, cognitive, and behavioral abnormalities. ASD is a complex disorder with a heterogeneous etiology. The genetic architecture of autism is such that a variety of different rare mutations have been discovered, including rare monogenic conditions that involve autistic symptoms. Also, de novo copy number variants and single nucleotide variants contribute to disease susceptibility. Finally, autosomal recessive loci are contributing to our understanding of inherited factors. We will review the progress that the field has made in the discovery of these rare genetic variants in autism. We argue that mutation discovery of this sort offers an important opportunity to identify neurodevelopmental mechanisms in disease. The hope is that these mechanisms will show some degree of convergence that may be amenable to treatment intervention.

show abstract

Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region

Cited by 174 publications

References 59 publications

The genomic basis of the Williams – Beuren syndrome

The genomic basis of the Williams – Beuren syndrome

NF1 microduplications: identification of seven nonrelated individuals provides further characterization of the phenotype

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms

Contact Info

Product

Resources

About