AUTHOR=Liu Yuefang , Wang Hui , Jin Xin , Shao Qixiang , Pan Qiong 

TITLE=Molecular Diagnosis and Prenatal Phenotype Analysis of Eight Fetuses With Ciliopathies

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.705808

DOI=10.3389/fgene.2021.705808

ISSN=1664-8021

ABSTRACT=<p>Human ciliopathies are hereditary conditions caused by variants in ciliary-associated genes. Ciliopathies are often characterized by multiple system defects. However, it is not easy to make a definite diagnosis in the prenatal period only based on the imageology. In this report, eight new prenatal cases from five unrelated families diagnosed with ciliopathies were systematically examined. The clinical manifestations of these fetuses showed such prenatal diagnostic features as occipital encephalocele, and polydactyly and polycystic kidneys. <italic>Situs inversus</italic> caused by <italic>CPLANE1</italic> variant was first reported. In Family 1 and Family 3, homozygous variants of <italic>CPLANE1</italic> and <italic>NPHP4</italic> caused by consanguineous marriage and uniparental disomy were detected by whole-exome sequencing, respectively. In Family 2, Family 4 and Family 5, compound heterozygotes of <italic>TMEM67</italic> and <italic>DYNC2H1</italic> including two novel missense variants and one novel nonsense variant were identified. The distribution of pathogenic missense variants along <italic>TMEM67</italic> gene mainly clustered in the extracellular cysteine rich region, extracellular area with unknown structure, and the transmembrane regions. Genotype-phenotype relationship between C<italic>PLANE1</italic> and <italic>TMEM67</italic> genes was concluded. This report describes new clinical manifestations and novel variants in <italic>CPLANE1</italic>, <italic>TMEM67</italic>, <italic>NPHP4</italic>, and <italic>DYNC2H1</italic>.</p>