Unusual Presentation in WAGR Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Diseases

Wang, Qiwei; Zhang, Xu‐Lin; Qin, Tingfeng; Wang, Dongni; Lin, Xiaoshan; Zhu, Yuanyuan; Tan, Haowen; Zhao, Lanqin; Li, Jing; Lin, Zhuoling; Lin, Zhuoling; Chen, Weirong

doi:10.3390/genes13081431

Cited by 4 publications

(2 citation statements)

References 20 publications

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“…Genomic DNA was extracted from participants’ peripheral leukocytes using a QIAamp DNA Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions. We performed WES for the proband via the Agilent v6 targeted sequence capture library process method with Illumina next-generation sequencing systems (NovaSeq 6000, Illumina Inc., San Diego, CA, USA), and bioinformatics analysis was performed as described previously [ 10 , 11 ]. Briefly, raw sequencing reads were matched to the human reference genome assembly (NCBI build 37/hg19) via Burrows-Wheeler Aligner.…”

Section: Methodsmentioning

confidence: 99%

“…To detect copy number variations (CNVs) and sub-microscopic deletions/duplications, we used the specific software package CNVkit based on the WES data [ 12 ]. A reliable CNV reference was trained using an iterative approach, as reported previously [ 10 ]. Following the detection of a CNV, whole-genome sequencing (WGS) was performed using the BGI MGISEQ-2000 sequencer platform to confirm the existence of the CNV.…”

Section: Methodsmentioning

confidence: 99%

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Whole-Exome Sequencing and Copy Number Analysis in a Patient with Warburg Micro Syndrome

Wang

Qin

Wang

et al. 2022

Genes

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Warburg Micro syndrome (WARBM) is an autosomal recessive neuro-ophthalmologic syndrome characterized by microcephaly, microphthalmia, congenital cataracts, cortical dysplasia, corpus callosum hypoplasia, spasticity, and hypogonadism. WARBM is divided into four subtypes according to the causative genes, of which RAB3GAP1 (OMIM# 602536) accounts for the highest proportion. We collected detailed medical records and performed whole-exome sequencing (WES) for a congenital cataract patient. A novel heterozygous frameshift RAB3GAP1 variant was detected in a boy with a rare ocular phenotype of bilateral membranous cataracts accompanied by a persistent papillary membrane. Further copy number variation (CNV) analysis identified a novel deletion on chromosome 2q21.3 that removed 4 of the 24 exons of RAB3GAP1. The patient was diagnosed with WARBM following genetic testing. The present study expands the genotypic and phenotypic spectrum of WARBM. It suggests applying whole exome sequencing (WES) and CNV analysis for the early diagnosis of syndromic diseases in children with congenital cataracts.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Whole-Exome Sequencing and Copy Number Analysis in a Patient with Warburg Micro Syndrome

Wang

Qin

Wang

et al. 2022

Genes

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Early Diagnosis of Syndromic Congenital Cataracts in a Large Cohort of Congenital Cataracts

Wang,

Qin

et al. 2024

American Journal of Ophthalmology

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Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients

Wang,

Lin,

Lai

et al. 2023

BMC Med Genomics

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Background Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal recessive pattern. To date, only four mutations have been reported to cause CLSD. This study aims to identify the disease-causing variants in a large cohort of congenital cataract patients, to expand the genotypic and phenotypic spectrum of CLSD, and to confirm the association between SEC23A and autosomal recessive CLSD (ARCLSD). Methods We collected detailed medical records and performed comprehensive ocular examinations and whole-exome sequencing (WES) on 115 patients with congenital cataracts. After suspecting that a patient may have CLSD based on the sequencing results, we proceeded to conduct transmission electron microscopy (TEM) on the cultured skin fibroblasts. The clinical validity of the reported gene-disease relationships for the gene and the disease was evaluated using the ClinGen gene curation framework. Results Two novel compound heterozygous variants (c.710A > C p.Asp237Ala, c.1946T > C p.Leu649Pro) of the SEC23A gene, classified as variant of uncertain significance, were identified in the proband with skeletal, cardiac, ocular, and hearing defects. The observation of typical distended endoplasmic reticulum cisternae further supported the diagnosis of CLSD. Application of the ClinGen gene curation framework confirmed the association between SEC23A and ARCLSD. Conclusion This study expands the genotypic and phenotypic spectrum of CLSD, proposes TEM as a supplemental diagnostic method, and indicates that congenital cataracts are a typical sign of ARCLSD.

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Unusual Presentation in WAGR Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Diseases

Cited by 4 publications

References 20 publications

Whole-Exome Sequencing and Copy Number Analysis in a Patient with Warburg Micro Syndrome

Whole-Exome Sequencing and Copy Number Analysis in a Patient with Warburg Micro Syndrome

Early Diagnosis of Syndromic Congenital Cataracts in a Large Cohort of Congenital Cataracts

Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients

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