@article{Antony_Gulec_Yilmaz_Gezdirici-Spect_Genet_Varia-2022,
author = {Antony, Dinu and Gulec Yilmaz, Elif and Gezdirici, Alper 
          and Slagter, Lennart and Bakey, Zeineb and Bornaun, Helen 
          and Tanidir, Ibrahim Cansaran and Van Dinh, Tran and 
          Brunner, Han G. and Walentek, Peter and Arnold, Sebastian J. 
          and Backofen, Rolf and Schmidts, Miriam},
title = {Spectrum of {Genetic} {Variants} in a {Cohort} of 37 
         {Laterality} {Defect} {Cases}},
journal = {Front Genet},
year = {2022},
doi = {10.3389/fgene.2022.861236},
volume = {13},
user = {backofen},
pmid = {35547246},
pages = {861236},
number = {},
issn = {1664-8021},
abstract = {Laterality defects are defined by the perturbed left-right 
            arrangement of organs in the body, occurring in a syndromal 
            or isolated fashion. In humans, primary ciliary dyskinesia 
            (PCD) is a frequent underlying condition of defective 
            left-right patterning, where ciliary motility defects also 
            result in reduced airway clearance, frequent respiratory 
            infections, and infertility. Non-motile cilia dysfunction 
            and dysfunction of non-ciliary genes can also result in 
            disturbances of the left-right body axis. Despite 
            long-lasting genetic research, identification of gene 
            mutations responsible for left-right patterning has remained 
            surprisingly low. Here, we used whole-exome sequencing with 
            Copy Number Variation (CNV) analysis to delineate the 
            underlying molecular cause in 35 mainly consanguineous 
            families with laterality defects. We identified causative 
            gene variants in 14 families with a majority of mutations 
            detected in genes previously associated with PCD, including 
            two small homozygous CNVs. None of the patients were 
            previously clinically diagnosed with PCD, underlining the 
            importance of genetic diagnostics for PCD diagnosis and 
            adequate clinical management. Identified variants in 
            non-PCD-associated genes included variants in PKD1L1 and 
            PIFO, suggesting that dysfunction of these genes results in 
            laterality defects in humans. Furthermore, we detected 
            candidate variants in GJA1 and ACVR2B possibly associated 
            with situs inversus. The low mutation detection rate of this 
            study, in line with other previously published studies, 
            points toward the possibility of non-coding genetic 
            variants, putative genetic mosaicism, epigenetic, or 
            environmental effects promoting laterality defects.}
}