Compound Heterozygous Variants in the IFT140 Gene Associated with Skeletal Ciliopathies

Area of Science:

• Genetics
• Developmental Biology
• Medical Genetics

Background:

• Ciliopathies are rare congenital disorders stemming from ciliary defects, leading to diverse clinical outcomes.
• Skeletal ciliopathies, a subset, significantly impact skeletal development with overlapping features like short stature and limb abnormalities.
• Known skeletal ciliopathies include short-rib polydactyly syndrome (SRPS), Jeune asphyxiating thoracic dystrophy (JATD), Mainzer-Saldino syndrome (MZSDS), and cranioectodermal dysplasia (CED).

Purpose of the Study:

• To report a fetal case extending the skeletal ciliopathy phenotype.
• To identify genetic variants associated with the observed phenotype.
• To broaden the understanding of IFT140 gene mutations and skeletal ciliopathy spectrum.

Main Methods:

• Phenotypic analysis of a fetus with multiple malformations.
• Genetic analysis to identify variants in the IFT140 gene.
• Review of existing literature on skeletal ciliopathies and IFT140 mutations.

Main Results:

• The affected fetus presented with an extended skeletal ciliopathy phenotype, including increased nuchal transparency, shortened/thickened long bones, hypoplastic tibia/fibula, absent bladder, flat nose, and frontal bossing.
• Compound heterozygous variants in the IFT140 gene were identified in the fetus.
• This expands the known mutation spectrum of IFT140 and the clinical presentation of skeletal ciliopathies.

Conclusions:

• The findings highlight the role of IFT140 in skeletal development and ciliopathies.
• This case expands the clinical spectrum of skeletal ciliopathies.
• Identification of these variants is crucial for prenatal diagnosis in at-risk pregnancies.