Interstitial deletion of chromosome 7q in a patient with Williams syndrome and infantile spasms

Mizugishi, Kiyomi; Yamanaka, Keiko; Kuwajima, Katsuko; Kondo, Ikuko

doi:10.1007/s100380050064

Cited by 34 publications

(34 citation statements)

References 18 publications

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“…The hypotonia noted in young children typically improves in childhood (Chapman et al 1996). Seizures are relatively rare aVecting <10% of individuals with WBS (Amenta et al 2005), and there are few reports of children with infantile spasms and hypsarrhythmia, usually associated with larger 7q11.23-q21.2 deletions involving the MAGI2 gene (Mizugishi et al 1998;Morimoto et al 2003;Trauner et al 1989;Tsao and Westman 1997).…”

Section: Neurological Problemsmentioning

confidence: 96%

Copy number variants at Williams–Beuren syndrome 7q11.23 region

et al. 2010

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Copy number variants (CNVs) of the Williams-Beuren syndrome (WBS) 7q11.23 region are responsible for neurodevelopmental disorders with multi-system involvement and variable expressivity. Typical features of WBS microdeletion comprise a recognizable pattern of facial dysmorphisms, supravalvular aortic stenosis, connective tissue abnormalities, hypercalcemia, and a distinctive neurobehavioral phenotype. Conversely, the phenotype of patients carrying the 7q11.23 reciprocal duplications includes less distinctive facial dysmorphisms and prominent speech delay. The common deletion/duplication ranges in size from 1.5 to 1.8 Mb and encompasses approximately 28 genes. This region is flanked by low copy repeats (LCRs) with greater than ~97% identity, which can mediate non-allelic homologous recombination resulting from misalignment of LCRs during meiosis. A clear genotype-phenotype correlation has been established in WBS only for the elastin gene, which is responsible for the vascular and connective tissue abnormalities. The molecular substrates underlying the other clinical features of 7q11.23 CNVs, including the neurocognitive phenotypes, are still debated. Recent studies suggest that besides the role of the genes in the deleted/duplicated interval, multiple factors such as regulatory sequences, epigenetic mechanisms, parental origin of the CNV, and nucleotide variations in the non-deleted/duplicated allele may be important in determining the variable expressivity of 7q11.23 CNV phenotypes. Here, we review the clinical and molecular findings and the recent insights on genomic disorders associated with CNVs involving the 7q11.23 region.

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Section: Neurological Problemsmentioning

confidence: 96%

Copy number variants at Williams–Beuren syndrome 7q11.23 region

et al. 2010

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“…Up to now it has not been possible to associate the presence of the WBS as the underlying cause of WS, although other cases showing both WBS and WS have been reported [Kahler et al, 1995;Tsao & Westman, 1997;Mizugishi et al, 1998]. …”

Section: To the Editormentioning

confidence: 98%

Williams–Beuren syndrome and West “syndrome:” Causal association or contiguous gene deletion syndrome?

Tercero

López

Herrero

et al. 2005

American J of Med Genetics Pt A

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“…Three genes-MAGI2 (MIM: 606382), HIP1 (MIM: 601767), and YWHAGhave been suggested as possible candidates for these atypical features. [46][47][48][49][50][51][52][53] Ramocki et al 51 suggested that haploinsufficiency of HIP1 is sufficient to alter neuronal homeostasis and cause focal and generalized epilepsies and cognitive dysfunction. However, their findings do not exclude the possibility that YWHAG loss of function is sufficient to cause neurological phenotypes alone, as proven by our results.…”

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confidence: 99%

De Novo Mutations in YWHAG Cause Early-Onset Epilepsy

Guella

McKenzie

Evans

et al. 2017

The American Journal of Human Genetics

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Massively parallel sequencing has revealed many de novo mutations in the etiology of developmental and epileptic encephalopathies (EEs), highlighting their genetic heterogeneity. Additional candidate genes have been prioritized in silico by their co-expression in the brain. Here, we evaluate rare coding variability in 20 candidates nominated with the use of a reference gene set of 51 established EE-associated genes. Variants within the 20 candidate genes were extracted from exome-sequencing data of 42 subjects with EE and no previous genetic diagnosis. We identified 7 rare non-synonymous variants in 7 of 20 genes and performed Sanger sequence validation in affected probands and parental samples. De novo variants were found only in SLC1A2 (aka EAAT2 or GLT1) (c.244G>A [p.Gly82Arg]) and YWHAG (aka 14-3-3g) (c.394C>T [p.Arg132Cys]), highlighting the potential cause of EE in 5% (2/42) of subjects. Seven additional subjects with de novo variants in SLC1A2 (n ¼ 1) and YWHAG (n ¼ 6) were subsequently identified through online tools. We identified a highly significant enrichment of de novo variants in YWHAG, establishing their role in early-onset epilepsy, and we provide additional support for the prior assignment of SLC1A2. Hence, in silico modeling of brain co-expression is an efficient method for nominating EE-associated genes to further elucidate the disorder's etiology and genotype-phenotype correlations.

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Interstitial deletion of chromosome 7q in a patient with Williams syndrome and infantile spasms

Cited by 34 publications

References 18 publications

Copy number variants at Williams–Beuren syndrome 7q11.23 region

Copy number variants at Williams–Beuren syndrome 7q11.23 region

Williams–Beuren syndrome and West “syndrome:” Causal association or contiguous gene deletion syndrome?

De Novo Mutations in YWHAG Cause Early-Onset Epilepsy

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