Clinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Cell Biology, School of Life Sciences, Central South University, Changsha, China.
J Hum Genet. 2022 Oct;67(10):573-577. doi: 10.1038/s10038-022-01053-w. Epub 2022 Jun 13.
Heterotaxy syndrome is a very rare congenital disease, which is caused by the disorder of left-right asymmetry during visceral development. However, pathogenic genetic lesions are found in less than 20% of HS patients. In this cohort study, whole-exome sequencing was performed for 110 patients with situs inversus or situs ambiguous. We identified a novel nonsense variant in PKD1L1(c.1387 C > T; p.463Gln*) in a Chinese patient with heterotaxy syndrome and congenital asplenia. This homozygous variant caused the domain of PKD1L1 complete absence. To our knowledge, this novel variant is the first phenotype of congenital asplenia found in patients with PKD1L1 variants, and the first PKD1L1 variant found in China. Our findings expand the spectrum of PKD1L1 variants and provide support for PKD1L1 variant and congenital asplenia, and the critical role of PKD1L1 during left-right patterning in the Han Chinese population.
异构综合征是一种非常罕见的先天性疾病，由内脏发育过程中左右不对称紊乱引起。然而，在不到 20%的 HS 患者中发现了致病的遗传病变。在这项队列研究中，对 110 例位置反转或位置不确定的患者进行了全外显子组测序。我们在中国一位异构综合征伴先天性无脾的患者中发现了 PKD1L1(c.1387 C > T; p.463Gln*)中的一个新的无义变异。这种纯合变异导致 PKD1L1 结构域完全缺失。据我们所知，这种新的变异是 PKD1L1 变异患者中发现的首例先天性无脾表型，也是中国首例 PKD1L1 变异。我们的发现扩展了 PKD1L1 变异的范围，并为 PKD1L1 变异和先天性无脾以及 PKD1L1 在汉族人群中左右模式形成中的关键作用提供了支持。
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