Whole exome sequencing reveals two novel mutations in GREB1L in two Chinese families with renal agenesis

Xie, F; Zhou, L; Luo, P; Xi, H; Yu, W; Ma, N; Wang, D; Peng, Y

doi:10.1093/qjmed/hcae036

QJM: An International Journal of Medicine

2024

DOI: 10.1093/qjmed/hcae036

|View full text |Cite

Whole exome sequencing reveals two novel mutations in GREB1L in two Chinese families with renal agenesis

F Xie,

L Zhou,

P Luo

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

A novel de novo synonymous variant in GREB1L impacts the mRNA splicing associated with aplasia of the urogenital system

Wang,

Yang

et al. 2024

American J of Med Genetics Pt A

View full text Add to dashboard Cite

GREB1‐like retinoic acid receptor coactivator (GREB1L) gene is associated with autosomal dominant renal hypodysplasia/aplasia 3 (RHDA3) and deafness, autosomal dominant 80 (DFNA80). Among the GREB1L variants reported, most of them are missense or frameshift, while no pathogenic synonymous variants have been recorded. Classical theory paid little attention to synonymous variants and classified it as nonpathogenic; however, recent studies suggest that the variants might be equally important. Here, we report a 7‐year‐old girl with new symptoms of clitoromegaly, uterovaginal, and ovarian agenesis as well as right kidney missing. A novel de novo GREB1L synonymous variant (NM_001142966: c.4731C>T, p.G1577=) was identified via whole exome sequencing. The variant was predicted to be disease‐causing through in silico analysis and was classified as likely pathogenic. Minigene splicing assays confirmed a 6 bp deletion in mutant cDNA comparing with the wild type, leading to two amino acids lost in GREB1L protein. Secondary and tertiary structure modeling showed alterations in protein structure. Our finding reveals a novel GREB1L variant with a new phenotype of urogenital system and is the first to report a pathogenic synonymous variant in GREB1L which affects mRNA splicing, suggesting synonymous variants cannot be ignored in prenatal diagnosis and genetic counseling.

show abstract

A novel de novo synonymous variant in GREB1L impacts the mRNA splicing associated with aplasia of the urogenital system

Wang,

Yang

et al. 2024

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Whole exome sequencing reveals two novel mutations in GREB1L in two Chinese families with renal agenesis

Cited by 1 publication

References 6 publications

A novel de novo synonymous variant in GREB1L impacts the mRNA splicing associated with aplasia of the urogenital system

A novel de novo synonymous variant in GREB1L impacts the mRNA splicing associated with aplasia of the urogenital system

Contact Info

Product

Resources

About