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Functional studies in yeast confirm the pathogenicity of a new GINS3 Meier-Gorlin syndrome variant.
Functional studies in yeast confirm the pathogenicity of a new GINS3 Meier-Gorlin syndrome variant.
- Source :
-
Clinical genetics [Clin Genet] 2024 Sep; Vol. 106 (3), pp. 342-346. Date of Electronic Publication: 2024 May 21. - Publication Year :
- 2024
-
Abstract
- Meier-Gorlin syndrome (MGORS) is an autosomal recessive disorder characterized by short stature, microtia, and patellar hypoplasia, and is caused by pathogenic variants of cellular factors involved in the initiation of DNA replication. We previously reported that biallelic variants in GINS3 leading to amino acid changes at position 24 (p.Asp24) cause MGORS. Here, we describe the phenotype of a new individual homozygous for the Asp24Asn variant. We also report the clinical characteristics of an individual harboring a novel homozygous GINS3 variant (Ile25Phe) and features suggestive of MGORS. Modification of the corresponding residue in yeast Psf3 (Val9Phe) compromised S phase progression compared to a humanized Psf3 Val9Ile variant. Expression of Psf3 Val9Phe in yeast also caused sensitivity to elevated temperature and the replicative stress-inducing drug hydroxyurea, confirming partial loss of function of this variant in vivo and allowing us to upgrade the classification of this variant. Taken together, these data validate the critical importance of the GINS DNA replication complex in the molecular etiology of MGORS.<br /> (© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)
- Subjects :
- Child
Female
Humans
Male
Chromosomal Proteins, Non-Histone genetics
DNA Replication genetics
Homozygote
Joint Instability genetics
Joint Instability pathology
Micrognathism genetics
Mutation
Nose abnormalities
Nose pathology
Phenotype
Saccharomyces cerevisiae genetics
Congenital Microtia genetics
Growth Disorders genetics
Growth Disorders pathology
Patella abnormalities
Patella pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1399-0004
- Volume :
- 106
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 38773883
- Full Text :
- https://doi.org/10.1111/cge.14545