Clinical findings in patients with GLI2 mutations--phenotypic variability

Area of Science:

• Genetics
• Developmental Biology
• Clinical Medicine

Background:

• Mutations in the human GLI2 gene are linked to pituitary and forebrain developmental defects, including holoprosencephaly (HPE) and related phenotypes.
• The GLI2 gene plays a critical role in embryonic development, influencing craniofacial and pituitary formation.

Purpose of the Study:

• To investigate the genetic basis of developmental anomalies in six Brazilian patients.
• To identify novel sequence variants in the GLI2 gene and characterize the associated clinical phenotypes.
• To explore the spectrum of GLI2-associated disorders, including previously unreported features.

Main Methods:

• Clinical evaluation of six Brazilian patients presenting with a range of developmental anomalies.
• Genetic analysis, including sequencing of the GLI2 gene, to identify causative variants.
• Phenotypic characterization, correlating genetic findings with clinical manifestations.

Main Results:

• Identification of novel sequence variants in the GLI2 gene in the studied patients.
• Observed phenotypic spectrum ranging from isolated cleft lip/palate with polydactyly and branchial arch anomalies to semi-lobar holoprosencephaly.
• Discovery of significant temporomandibular joint (TMJ) involvement in patients with GLI2 mutations, representing a new clinical finding.

Conclusions:

• GLI2 gene mutations are associated with a broader spectrum of developmental abnormalities than previously recognized.
• Temporomandibular joint (TMJ) anomalies should be considered in the clinical evaluation of patients with GLI2 gene mutations.
• Further research is warranted to fully elucidate the genotype-phenotype correlations and clinical implications of GLI2 variants.