Compound heterozygous splicing variants in KIAA0586 cause fetal short-rib thoracic dysplasia and cerebellar malformation: Use of exome sequencing in prenatal diagnosis.

ABSTRACT:

Background

Short-rib thoracic dysplasia (SRTD) and Joubert syndrome (JS) are rare genetic ciliopathies, and individuals with either syndrome can manifest cerebellar malformation and variable developmental delays. However, neither of these conditions is easily diagnosed during pregnancy due to a limited fetal phenotype. Here, we investigated a fetus that was initially observed to have short limbs and polydactyly and discovered a compound heterozygous pathogenesis through exome sequencing (ES).

Methods

Simultaneous trio-ES and chromosome microarray analysis was provided for the fetus. The presence and effects of these variants on splicing were further validated at the DNA and RNA levels.

Results

Only short limbs and post-axial polydactyly of the fetus were detected duri

SUBMITTER: Zhao Q 

PROVIDER: S-EPMC10009908 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature