1 IntroductionPrimary cilia are antenna-like organelles extending from the surface of various eukaryotic cells; they are able to sense external signals and relay developmental and homeostatic signaling pathways[1, 2]. Their complex structure may consist of over 1000 proteins[3], and mutations in ciliary protein genes leading to defective ciliary proteins can cause a group of diseases known as ciliary disorders. These diseases exhibit high clinical and genetic heterogeneity and can affect multiple tissues and organs, such as the brain, kidneys, eyes, liver, and skeleton, and are sometimes associated with features such as organ reversal and polydactyly[4].Skeletal ciliopathies are a group of rare genetic disorders of skeletal development arising from defects in primary cilia. Among them, short rib thoracic dysplasia (SRTD) encompasses a range of skeletal dysplasias characterized primarily by short limbs, narrow thorax, and associated visceral abnormalities. These include short rib-polydactyly syndrome (SRPS); asphyxiating thoracic dystrophy (ATD, also known as Jeune syndrome); Ellis-van Creveld syndrome (EVC); Mainzer-Saldino syndrome (MZSDS); and cranioectodermal dysplasia (CED). The severity of different subtypes of SRTD varies significantly, ranging from relatively mild to lethal, with most being autosomal recessive disorders[5-7]. Because SRTD has complex and varied symptoms and strong genetic heterogeneity, diagnosing it is very challenging[8, 9], and classification is primarily based on potential pathogenic genes[10]. Currently, there are 19 reported pathogenic genes for SRTD in the OMIM database, and accurate genetic diagnosis is essential for clinical classification and treatment of SRTD patients, as well as for prenatal diagnosis of the disease.In this study, we describe a Han Chinese family with a history of four adverse pregnancies, demonstrating that the ultrasound findings of the fetuses in the last two pregnancies were consistent with SRTD. We performed prenatal diagnosis using a series of genetic tests, including clinical exome sequencing; ultimately, we identified a novel homozygous variant in the DYNC2I1 gene. We systematically analyzed the pathogenicity of this variant according to ACMG guidelines and discussed the feasibility of using clinical exome sequencing for prenatal diagnosis related to this variant.