<scp><i>HECW2</i></scp>‐related disorder in four Japanese patients

Yanagishita, Tomoe; Hirade, Takuya; Yamamoto, Kiyomi; Funatsuka, Makoto; Miyamoto, Yusaku; Maeda, Makiko; Yanagi, Kumiko; Kaname, Tadashi; Nagata, Satoru; Nagata, Masanobu; Ishihara, Yasuki; Miyashita, Yohei; Asano, Yoshihiro; Sakata, Yasushi; Kosaki, Kenjiro; Yamamoto, Toshiyuki

doi:10.1002/ajmg.a.62363

Cited by 8 publications

(3 citation statements)

References 17 publications

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“…However, microdeletion of 2q32.3-q33.1 is not known to cause severe developmental disorders. Hence, the neurodevelopmental disorders due to HECW2 mutations are considered to be because of the dominant negative effect [36].…”

Section: Genes Whose Phenotypes Are Not Affected By Genomic Copy Number Changesmentioning

confidence: 99%

Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders

Yamamoto

2021

Cells

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Genomic studies are increasingly revealing that neurodevelopmental disorders are caused by underlying genomic alterations. Chromosomal microarray testing has been used to reliably detect minute changes in genomic copy numbers. The genes located in the aberrated regions identified in patients with neurodevelopmental disorders may be associated with the phenotypic features. In such cases, haploinsufficiency is considered to be the mechanism, when the deletion of a gene is related to neurodevelopmental delay. The loss-of-function mutation in such genes may be evaluated using next-generation sequencing. On the other hand, the patients with increased copy numbers of the genes may exhibit different clinical symptoms compared to those with loss-of-function mutation in the genes. In such cases, the additional copies of the genes are considered to have a dominant negative effect, inducing cell stress. In other cases, not the copy number changes, but mutations of the genes are responsible for causing the clinical symptoms. This can be explained by the dominant negative effects of the gene mutations. Currently, the diagnostic yield of genomic alterations using comprehensive analysis is less than 50%, indicating the existence of more subtle alterations or genomic changes in the untranslated regions. Copy-neutral inversions and insertions may be related. Hence, better analytical algorithms specialized for the detection of such alterations are required for higher diagnostic yields.

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Section: Genes Whose Phenotypes Are Not Affected By Genomic Copy Number Changesmentioning

confidence: 99%

Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders

Yamamoto

2021

Cells

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“…This missense variant was located in the C-terminal HECT domain of HECW2 and has been reported in another patient with NDHSAL in ClinVar (VCV001320205.1). A different missense change at the same codon (p.Leu1448Trp) has also been reported as likely pathogenic (ClinVar ID: VCV000801845.1) 8 . This missense variant was absent from the controls in public databases, such as the Exome Variant Server ( http://evs.gs.washington.edu/EVS/ ), dbSNP ( http://www.ncbi.nlm.nih.gov/snp/ ), and Genome Aggregation Database (gnomAD, https://gnomad.broadinstitute.org/ ).…”

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confidence: 99%

A novel HECW2 variant in an infant with congenital long QT syndrome

et al. 2023

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Pathogenic variants of HECW2 have been reported in cases of neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL; OMIM #617268). A novel HECW2 variant (NM_001348768.2:c.4343 T > C,p.Leu1448Ser) was identified in an NDHSAL infant with severe cardiac comorbidities. The patient presented with fetal tachyarrhythmia and hydrops and was postnatally diagnosed with long QT syndrome. This study provides evidence that HECW2 pathogenic variants can cause long QT syndrome along with neurodevelopmental disorders.

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“…Due to the patient’s unclear diagnosis, we enrolled her in the “Initiative on Rare and Undiagnosed Diseases” (IRUD) research project 2 , 3 . This study was performed in accordance with the Declaration of Helsinki and was approved by the ethics committee of our institution.…”

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Recurrent de novo pathogenic variant of WASF1 in a Japanese patient with neurodevelopmental disorder with absent language and variable seizures

et al. 2021

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A recurrent de novo pathogenic variant of WASF1, NM_003931:c.1516C>T [p.Arg506*], was identified in a 6-year-old female Japanese patient with severe developmental delay, hypotonia, hyperkinetic behavior, and distinctive facial features. The initial report of five adult patients with WASF1 variants was the only previous report regarding variants of this gene; this is the second such report, reaffirming that rare but recurrent truncating variants of WASF1 are associated with severe neurodevelopmental disorders.

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HECW2‐related disorder in four Japanese patients

Cited by 8 publications

References 17 publications

Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders

Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders

A novel HECW2 variant in an infant with congenital long QT syndrome

Recurrent de novo pathogenic variant of WASF1 in a Japanese patient with neurodevelopmental disorder with absent language and variable seizures

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