Jul 2026· Human Genetics· Vol 145· 0 citations· 37 references
Medicine
TL;DR
This study provides the first definitive evidence that a synonymous DHCR7 variant can act as a likely pathogenic allele through splicing disruption and offers critical molecular insight and a refined framework for interpreting synonymous variants—particularly variants of uncertain significance—with important implications for clinical diagnosis, genetic counseling, and prenatal care.
A homozygous synonymous NPR2 variant is identified in an individual with AMDM and aberrant splicing induced by a synonymous variant as a disease-causing mechanism affecting a core developmental signaling pathway is established.
N. B. Acikgoz, Hasan Basri Kılıç, Gizem Urel Demir et al.· Differentiation; research in...· 0 citations
The
SF1
gene encodes the splicing factor 1, a part of the splicing machinery. Recently, loss-of-function (LoF) variants in the
SF1
gene have been suggested as a molecular cause of a neurodevelopmental spliceosomopathy.
We report a unique familial case of a novel truncating variant in a single Czech family presenting with mild neurodevelopmental disorders (NDD) and variable congenital abnormalities. The c.1764_1776del variant in the last exon of the
SF1
gene (NM_004630.4) was identified through exome sequencing in three affected family members. Functional analyses at the transcriptional level confirmed that this alteration does not trigger nonsense-mediated decay (NMD), and aberrant transcripts with premature termination codons are preserved.
This study expands the spectrum of pathogenic variants involved in the development of new
SF1
-related spliceosomopathy and its diverse phenotypic effects. Our data emphasise the clinical benefits of comprehensive exome sequencing for uncovering new gene-disease connections.
M. Wayhelova, J. Šoukalová, Petra Lišková et al.· Orphanet Journal of Rare Dis...· 0 citations
These findings expand the variant spectrum of COL5A2, improving molecular diagnosis of cEDS, and validate the pathogenicity of an unreported COL5A2 intronic variant in a Chinese family with cEDS.
Findings supported the classification of the TP53 germline variant c.671A>C (p.E224A) as likely pathogenic, providing a definitive molecular diagnosis for family counselling and sheds light on how certain predicted TP53 missense variants can be linked to disease mechanisms through RNA splicing disruption.
I. Velkova, Serena Cappato, Daniela Rivera et al.· Scientific Reports· 0 citations
A Chinese patient presenting with classic hallmarks of MGORS7 alongside atypical clinical features, including hearing and visual impairments is reported, suggesting that growth hormone therapy may be beneficial for growth retardation in patients with MGORS7.
Ying Zhao, Yi-Yang Fu, Shu-Ying Zhang et al.· Frontiers in Genetics· 0 citations
The genotypic and phenotypic spectrum of NMOAS is expanded, the pathogenic role of this variant in splicing dysregulation is confirmed, and the need for long-term monitoring of emerging comorbidities in affected patients is emphasized.
Yue Shen, Yunyu Zhou, Chao Lu et al.· Clinical Genetics· 0 citations
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