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A novel nonsense PKD1L1 variant cause heterotaxy syndrome with congenital asplenia in a Han Chinese patient


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.

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  1. Hamada H. Molecular and cellular basis of left-right asymmetry in vertebrates. Proc Jpn Acad Ser B Phys Biol Sci. 2020;96:273–96.

    CAS  Article  Google Scholar 

  2. Sempou E, Khokha MK. Genes and mechanisms of heterotaxy: patients drive the search. Curr Opin Genet Dev. 2019;56:34–40.

    CAS  Article  Google Scholar 

  3. Postema MC, Carrion-Castillo A, Fisher SE, Vingerhoets G, Francks C. The genetics of situs inversus without primary ciliary dyskinesia. Sci Rep. 2020;10:3677.

    CAS  Article  Google Scholar 

  4. Lin AE, Krikov S, Riehle-Colarusso T, Frias JL, Belmont J, Anderka M, et al. Laterality defects in the national birth defects prevention study (1998-2007): birth prevalence and descriptive epidemiology. Am J Med Genet A 2014;164A:2581–91.

    Article  Google Scholar 

  5. Gebbia M, Ferrero GB, Pilia G, Bassi MT, Aylsworth A, Penman-Splitt M, et al. X-linked situs abnormalities result from mutations in ZIC3. Nat Genet. 1997;17:305–8.

    CAS  Article  Google Scholar 

  6. Bamford RN, Roessler E, Burdine RD, Saplakoglu U, dela Cruz J, Splitt M, et al. Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects. Nat Genet. 2000;26:365–9.

    CAS  Article  Google Scholar 

  7. Yuasa T, Venugopal B, Weremowicz S, Morton CC, Guo L, Zhou J. The sequence, expression, and chromosomal localization of a novel polycystic kidney disease 1-like gene, PKD1L1, in human. Genomics 2002;79:376–86.

    CAS  Article  Google Scholar 

  8. Vogel P, Read R, Hansen GM, Freay LC, Zambrowicz BP, Sands AT. Situs inversus in Dpcd/Poll-/-, Nme7-/-, and Pkd1l1-/- mice. Vet Pathol. 2010;47:120–31.

    CAS  Article  Google Scholar 

  9. Vetrini F, D’Alessandro LC, Akdemir ZC, Braxton A, Azamian MS, Eldomery MK, et al. Bi-allelic mutations in PKD1L1 are associated with laterality defects in humans. Am J Hum Genet. 2016;99:886–93.

    CAS  Article  Google Scholar 

  10. Lucas JS, Barbato A, Collins SA, Goutaki M, Behan L, Caudri D, et al. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur Respir J. 2017;49.

  11. Quinodoz M, Peter VG, Bedoni N, Royer Bertrand B, Cisarova K, Salmaninejad A, et al. AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data. Nat Commun. 2021;12:518.

    CAS  Article  Google Scholar 

  12. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.

    Article  Google Scholar 

  13. Matsui T, Bessho Y. Left-right asymmetry in zebrafish. Cell Mol Life Sci. 2012;69:3069–77.

    CAS  Article  Google Scholar 

  14. Kurkowiak M, Zietkiewicz E, Witt M. Recent advances in primary ciliary dyskinesia genetics. J Med Genet. 2015;52:1–9.

    CAS  Article  Google Scholar 

  15. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N. Engl J Med. 2011;364:1533–43.

    CAS  Article  Google Scholar 

  16. Field S, Riley KL, Grimes DT, Hilton H, Simon M, Powles-Glover N, et al. Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2. Development 2011;138:1131–42.

    CAS  Article  Google Scholar 

  17. McGrath J, Somlo S, Makova S, Tian X, Brueckner M. Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 2003;114:61–73.

    CAS  Article  Google Scholar 

  18. Kamura K, Kobayashi D, Uehara Y, Koshida S, Iijima N, Kudo A, et al. Pkd1l1 complexes with Pkd2 on motile cilia and functions to establish the left-right axis. Development 2011;138:1121–9.

    CAS  Article  Google Scholar 

  19. Grimes DT, Keynton JL, Buenavista MT, Jin X, Patel SH, Kyosuke S, et al. Genetic analysis reveals a hierarchy of interactions between polycystin-encoding genes and genes controlling cilia function during left-right determination. PLoS Genet. 2016;12:e1006070.

    Article  Google Scholar 

  20. England SJ, Campbell PC, Banerjee S, Swanson AJ, Lewis KE. Identification and expression analysis of the complete family of Zebrafish pkd genes. Front Cell Dev Biol. 2017;5:5.

    Article  Google Scholar 

  21. Berauer JP, Mezina AI, Okou DT, Sabo A, Muzny DM, Gibbs RA, et al. Identification of polycystic kidney disease 1 like 1 gene variants in children with biliary atresia splenic malformation syndrome. Hepatology 2019;70:899–910.

    CAS  Article  Google Scholar 

  22. Rodriguez S, Chaturvedi R, Blanchette V, Dell S, Axford M, Cada M, et al. PKD1L1-related situs inversus associated with sideroblastic anemia. Clin Genet. 2019;95:629–30.

    CAS  Article  Google Scholar 

  23. Le Fevre A, Baptista J, Ellard S, Overton T, Oliver A, Gradhand E, et al. Compound heterozygous Pkd1l1 variants in a family with two fetuses affected by heterotaxy and complex Chd. Eur J Med Genet. 2020;63:103657.

    Article  Google Scholar 

  24. Correa ARE, Endrakanti M, Naini K, Kabra M, Gupta N. Hydrops fetalis in PKD1L1-related heterotaxy: Report of two foetuses and expanding the phenotypic and molecular spectrum. Ann Hum Genet. 2021;85:138–45.

    CAS  Article  Google Scholar 

  25. Loomba RS, Geddes GC, Basel D, Benson DW, Leuthner SR, Hehir DA, et al. Bacteremia in patients with heterotaxy: a review and implications for management. Congenit Heart Dis. 2016;11:537–47.

    Article  Google Scholar 

  26. De Luca A, Sarkozy A, Consoli F, Ferese R, Guida V, Dentici ML, et al. Familial transposition of the great arteries caused by multiple mutations in laterality genes. Heart 2010;96:673–7.

    Article  Google Scholar 

  27. Escobar-Diaz MC, Friedman K, Salem Y, Marx GR, Kalish BT, Lafranchi T, et al. Perinatal and infant outcomes of prenatal diagnosis of heterotaxy syndrome (asplenia and polysplenia). Am J Cardiol. 2014;114:612–7.

    Article  Google Scholar 

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We sincerely appreciate all the participants in this project.



This work was supported by the National Natural Science Foundation of China (81970268 and 81470445).

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Correspondence to Zhi-Ping Tan.

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Gu, H., Yuan, ZZ., Xie, XH. et al. A novel nonsense PKD1L1 variant cause heterotaxy syndrome with congenital asplenia in a Han Chinese patient. J Hum Genet (2022).

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