Refinement of the genomic structure of <i>STX1A</i> and mutation analysis in nondeletion Williams syndrome patients

Wu, Yuanqing; Bejjani, Bassem A.; Tsui, Lap‐Chee; Mandel, Ariane; Osborne, Lucy R.; Shaffer, Lisa G.

doi:10.1002/ajmg.10321

Cited by 5 publications

(8 citation statements)

References 18 publications

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“…The lack of STX1A mutations in five patients, who have WBS but no detectable microdeletion at 7q11.23, supports this idea. 23 Nevertheless, we cannot completely exclude that the partial telomeric deletions cause a position effect on the neighbouring chromosome region and may mimic haploinsufficiency for the complete set of genes in the 1.5 Mb WBSCR. The idea of a position effect is discussed in the recent publication of a spontaneously occurring familial translocation with disruption of the ELN gene in intron 5.…”

Section: Discussionmentioning

confidence: 95%

“…23 including the elastin locus (ELN). 1 2 The classical WBS phenotype comprises elastin arteriopathy (supravalvular aortic stenosis and/or peripheral pulmonary stenosis), connective tissue abnormalities (for example, abnormal joint mobility, hernia and diverticula, hoarse voice), and a particular facial appearance (supraorbital fullness, stellate pattern of the iris, short nose with long philtrum, full lips, and wide mouth).…”

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confidence: 99%

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Partial deletion of the critical 1.5 Mb interval in Williams-Beuren syndrome

Heller

Rauch²,

Lüttgen³

et al. 2003

Journal of Medical Genetics

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W illiams-Beuren syndrome (WBS, OMIM 194050) is a microdeletion syndrome caused by hemizygosity for multiple genes in 7q11.23 including the elastin locus (ELN).1 2 The classical WBS phenotype comprises elastin arteriopathy (supravalvular aortic stenosis and/or peripheral pulmonary stenosis), connective tissue abnormalities (for example, abnormal joint mobility, hernia and diverticula, hoarse voice), and a particular facial appearance (supraorbital fullness, stellate pattern of the iris, short nose with long philtrum, full lips, and wide mouth). Other frequent features are growth and psychomotor retardation with muscular hypotonia, limited visuospatial cognition, and specific language as well as behavioural abnormalities (overfriendliness and anxiety disorders, hypersensitivity to sounds).3-5 Endocrine and metabolic disturbances (infantile hypercalcaemia) may occur.Despite at least 21 genes having been identified in the common 1.5 Mb deletion interval in humans, 6 their individual contribution to the multisystem phenotype of WBS is unclear. So far, only the gene coding for elastin (ELN) has been proven to be causally involved 7 : ELN is deleted in all WBS patients with a microdeletion 7q11.23 who have been reported to date. However, hemizygosity for ELN alone does not cause WBS, but isolated supravalvular aortic stenosis (SVAS).8 Hence, haploinsufficiency for ELN is necessary but not sufficient for WBS.Molecular dissection of the WBS phenotype is hindered by the fact that over 95% of patients with the classical phenotype carry an apparently identical ∼1.5 Mb deletion interval.9-11 This constant size is explained by non allelic-homologous recombination between duplicons flanking the deletion interval.12 The presence of these direct repeats is assumed to be a predisposing factor for the WBS microdeletion that occurs with a frequency of approximately 1 in 20 000 liveborn children. 12So far, several cases of either classical WBS or SVAS with or without cognitive deficits have been found to be associated with a smaller deletion. In seven of these cases an alternative proximal breakpoint was involved, and an eighth case featured an alternative distal breakpoint [13][14][15][16] (reviewed in Osborne 2 ). We present a further independent case with an atypical deletion but with the classical WBS phenotype. Together, these cases indicate that the critical WBS region is smaller than 1.5 Mb. CASE REPORT AND METHODSThe patient and his healthy twin sister were born to non-consanguineous parents (maternal age 26, paternal age 41) after an uneventful pregnancy. Birth weight, height, and head circumference were within the normal range for twins. The constellation of supravalvular aortic stenosis, pulmonary Key points• We present the case of a patient with the classical phenotype of Williams-Beuren syndrome who has only a partial deletion of the common 1.5 Mb deletion interval at 7q11.23.• Fluorescence in situ hybridisation (FISH) with the commercial WBSCR probe (from Appligene/Oncor) showed two specific signals in each metaphas...

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Partial deletion of the critical 1.5 Mb interval in Williams-Beuren syndrome

Heller

Rauch²,

Lüttgen³

et al. 2003

Journal of Medical Genetics

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“…The chromosome 7q21.1-q21.3 (Blouin et al 1998) and 7q21.3-q22 (Faraone et al 1998) regions have been linked to schizophrenia but are quite far from the STX1A gene; however, there is evidence that STX1A may affect behavior in disorders such as Williams syndrome (WS). WS is a neurodevelopmental, chromosomal-deletion disorder that may involve the STX1A gene region (Botta et al 1999b;Nakayama et al 1998), although recent evidence suggests that the STX1A gene is not always deleted (Botta et al 1999a;Tassabehji et al 1999;Wu et al 2002). Clinical features of the syndrome include: dysmorphic facies, mental retardation or learning difficulties, elastin arteriopathy, a unique cognitive profile of relative strength in auditory rote memory and language and extreme weakness in visuospatial constructive cognition, and a typical personality that includes overfriendliness, anxiety, and attention problems (Morris and Mervis 2000).…”

Section: Discussionmentioning

confidence: 99%

Association between schizophrenia and the syntaxin 1A gene

Wong

Trakalo

Likhodi

et al. 2004

Biological Psychiatry

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“…Reference lists of journal studies were used to find further relevant journal articles. After obtaining journal permissions, photos of individuals with WBS were used to supplement study participants described below (Delgado et al, 2013; Honjo et al, 2015; Jiang & Liu, 2015; Lumaka et al, 2016; Mazumdar, Sarkar, Badveli, & Majumder, 2016; Morris, 1993, 2010; Patil, Madhusudhan, Shah, & Suresh, 2012; Sakhuja, Whyte, Kamath, Martin, & Chitayat, 2015; Smoot, Zhang, Klaiman, Schultz, & Pober, 2005; Tekendo-Ngongang et al, 2014; van Kogelenberg et al, 2010; Wu et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

Williams–Beuren syndrome in diverse populations

Kruszka

Porras

Souza

et al. 2018

American J of Med Genetics Pt A

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Williams-Beuren syndrome (WBS) is a common microdeletion syndrome characterized by a 1.5Mb deletion in 7q11.23. The phenotype of WBS has been well described in populations of European descent with not as much attention given to other ethnicities. In this study, individuals with WBS from diverse populations were assessed clinically and by facial analysis technology. Clinical data and images from 137 individuals with WBS were found in 19 countries with an average age of 11 years and female gender of 45%. The most common clinical phenotype elements were periorbital fullness and intellectual disability which were present in greater than 90% of our cohort. Additionally, 75% or greater of all individuals with WBS had malar flattening, long philtrum, wide mouth, and small jaw. Using facial analysis technology, we compared 286 Asian, African, Caucasian, and Latin American individuals with WBS with 286 gender and age matched controls and found that the accuracy to discriminate between WBS and controls was 0.90 when the entire cohort was evaluated concurrently. The test accuracy of the facial recognition technology increased significantly when the cohort was analyzed by specific ethnic population (P-value < 0.001 for all comparisons), with accuracies for Caucasian, African, Asian, and Latin American groups of 0.92, 0.96, 0.92, and 0.93, respectively. In summary, we present consistent clinical findings from global populations with WBS and demonstrate how facial analysis technology can support clinicians in making accurate WBS diagnoses.

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Refinement of the genomic structure of STX1A and mutation analysis in nondeletion Williams syndrome patients

Cited by 5 publications

References 18 publications

Partial deletion of the critical 1.5 Mb interval in Williams-Beuren syndrome

Partial deletion of the critical 1.5 Mb interval in Williams-Beuren syndrome

Association between schizophrenia and the syntaxin 1A gene

Williams–Beuren syndrome in diverse populations

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