AI Article Synopsis
- GLI2 is a transcription factor crucial for the Hedgehog pathway, and mutations can lead to conditions like holoprosencephaly and polydactylism.
- Exome sequencing of a trio from an affected Italian family identified a novel deletion in GLI2 that affects its function.
- The study demonstrates the importance of understanding the diverse clinical impacts of GLI2 mutations and suggests that functional assays can aid in genetic diagnosis and counseling.
Article Abstract
Background: GLI2 encodes for a transcription factor that controls the expression of several genes in the Hedgehog pathway. Mutations in GLI2 have been described as causative of a spectrum of clinical phenotypes, notably holoprosencephaly, hypopituitarism and postaxial polydactyl.
Methods: In order to identify causative genetic variant, we performed exome sequencing of a trio from an Italian family with multiple affected individuals presenting clinical phenotypes in the Culler-Jones syndrome spectrum. We performed a series of cell-based assays to test the functional properties of mutant GLI2.
Results: Here we report a novel deletion c.3493delC (p.P1167LfsX52) in the C-terminal activation domain of GLI2. Functional assays confirmed the pathogenicity of the identified variant and revealed a dominant-negative effect of mutant GLI2 on Hedgehog signalling.
Conclusions: Our results highlight the variable clinical manifestation of GLI2 mutations and emphasize the value of functional characterisation of novel gene variants to assist genetic counselling and diagnosis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328167 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210097 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
[Culler-Jones syndrome caused by a new mutated GLI2 gene: a case report].
Zhonghua Nei Ke Za Zhi
December 2023
Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Case report: A case of Culler-Jones syndrome caused by a novel mutation of gene and literature review.
Front Endocrinol (Lausanne)
March 2023
Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, China.
Culler-Jones syndrome is a rare clinical phenomenon with diverse manifestations and is prone to misdiagnosis. We report one patient who presented with a 10-year history of anosmia and a 1-year history of epididymal pain. Kallmann syndrome was suspected initially.
View Article and Find Full Text PDF[Clinical and genetic analysis of a child with Culler-Jones syndrome due to variant of GLI2 gene].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
February 2023
Ningbo Women & Children's Hospital, Ningbo, Zhejiang 315000, China.
Objective: To explore the genetic basis for a child featuring short stature and postaxial polydactyly.
Methods: A child who presented at Ningbo Women & Children's Hospital in May 2021 due to the"discovery of growth retardation for more than two years" was selected as the subject. Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA.
Truncating and zinc-finger variants in GLI2 are associated with hypopituitarism.
Am J Med Genet A
April 2022
Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Variants in transcription factor GLI2 have been associated with hypopituitarism and structural brain abnormalities, occasionally including holoprosencephaly (HPE). Substantial phenotypic variability and nonpenetrance have been described, posing difficulties in the counseling of affected families. We present three individuals with novel likely pathogenic GLI2 variants, two with truncating and one with a de novo missense variant p.
View Article and Find Full Text PDFThis case series and review of the literature support that patients with pathogenic variants of the GLI2 gene demonstrate an autosomal dominant inheritance pattern, variable expressivity, and incomplete penetrance.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!