Identification of a Novel Variant in a Patient with Primary Ciliary Dyskinesia

Overview

Journal Pharmgenomics Pers Med

Publisher Dove Medical Press

Date 2022 Jul 18

PMID 35847568

Authors

Binyi Yang

Cheng Lei

Danhui Yang

Chenyang Lu

Yingjie Xu

Lin Wang

Ting Guo

Rongchun Wang

Hong Luo

Affiliations

Soon will be listed here.

Abstract

Background: encodes a protein with 1012 amino acids, which is a component of basal bodies and centrioles, essential for cilia biogenesis. was reported to be associated with X-chromosome linked dysmorphology syndrome in early studies and recent studies reported a few cases with primary ciliary dyskinesia (PCD) caused by deficiency.

Case Presentation: We report a 31-year-old man who suffered from recurrent respiratory infections with typical manifestations of primary ciliary dyskinesia. In addition to respiratory manifestations, the patient also had situs inversus, obesity, gastroesophageal reflux, and hearing impairment. Clubbing fingers and mild streblomicrodactyly were also observed.

Examination Result: We performed whole-exome sequencing to identify a novel variant c.2795delA:p.(Lys932Argfs*3) in . The hemizygous variant was predicted to be likely pathogenic by bioinformatic analysis software and ACMG guideline. High-speed video microscopy (HSVM), transmission electron microscopy (TEM), and immunofluorescence were performed to analyze the respiratory cilia. A high beating frequency and a stiff beating pattern were observed under HSVM, while there were no significant abnormalities in TEM and immunofluorescence. The sperm flagella examinations were also generally normal.

Conclusion: Our study identified a novel frameshift variant in causing PCD, enriched the genetic spectrum of variants, and verified that mutation can lead to only a PCD characteristic phenotype, while other -associated syndromic symptoms such as dysmorphic features and renal symptoms were not present.

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References

Zariwala M, Knowles M, Omran H . Genetic defects in ciliary structure and function. Annu Rev Physiol. 2006; 69:423-50. DOI: 10.1146/annurev.physiol.69.040705.141301. View

Cooper T, Noonan E, von Eckardstein S, Auger J, Baker H, Behre H . World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2009; 16(3):231-45. DOI: 10.1093/humupd/dmp048. View

Collins S, Gove K, Walker W, Lucas J . Nasal nitric oxide screening for primary ciliary dyskinesia: systematic review and meta-analysis. Eur Respir J. 2014; 44(6):1589-99. DOI: 10.1183/09031936.00088614. View

Fauth C, Toutain A . Comment on "Whole exome sequencing and array-based molecular karyotyping as aids to prenatal diagnosis in fetuses with suspected Simpson-Golabi-Behmel syndrome". Prenat Diagn. 2017; 37(10):1055-1056. DOI: 10.1002/pd.5137. View

Guo Z, Chen W, Wang L, Qian L . Clinical and Genetic Spectrum of Children with Primary Ciliary Dyskinesia in China. J Pediatr. 2020; 225:157-165.e5. DOI: 10.1016/j.jpeds.2020.05.052. View

Sampaio P, da Silva M, Vale I, Roxo-Rosa M, Pinto A, Constant C . CiliarMove: new software for evaluating ciliary beat frequency helps find novel mutations by a Portuguese multidisciplinary team on primary ciliary dyskinesia. ERJ Open Res. 2021; 7(1). PMC: 8174773. DOI: 10.1183/23120541.00792-2020. View

Goutaki M, Meier A, Halbeisen F, Lucas J, Dell S, Maurer E . Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis. Eur Respir J. 2016; 48(4):1081-1095. DOI: 10.1183/13993003.00736-2016. View

Tang Z, Lin M, Stowe T, Chen S, Zhu M, Stearns T . Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites. Nature. 2013; 502(7470):254-7. PMC: 4075283. DOI: 10.1038/nature12606. View

Budny B, Chen W, Omran H, Fliegauf M, Tzschach A, Wisniewska M . A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Hum Genet. 2006; 120(2):171-8. DOI: 10.1007/s00439-006-0210-5. View

10.

PAPILLON-LEAGE , PSAUME J . [Abnormalities of the buccal frena]. Actual Odontostomatol (Paris). 1954; 8(25):7-26. View

11.

Leigh M, Pittman J, Carson J, Ferkol T, Dell S, Davis S . Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet Med. 2009; 11(7):473-87. PMC: 3739704. DOI: 10.1097/GIM.0b013e3181a53562. View

12.

Bustamante-Marin X, Yin W, Sears P, Werner M, Brotslaw E, Mitchell B . Lack of GAS2L2 Causes PCD by Impairing Cilia Orientation and Mucociliary Clearance. Am J Hum Genet. 2019; 104(2):229-245. PMC: 6372263. DOI: 10.1016/j.ajhg.2018.12.009. View

13.

Hannah W, DeBrosse S, Kinghorn B, Strausbaugh S, Aitken M, Rosenfeld M . The expanding phenotype of OFD1-related disorders: Hemizygous loss-of-function variants in three patients with primary ciliary dyskinesia. Mol Genet Genomic Med. 2019; 7(9):e911. PMC: 6732318. DOI: 10.1002/mgg3.911. View

14.

Wallmeier J, Nielsen K, Kuehni C, Lucas J, Leigh M, Zariwala M . Motile ciliopathies. Nat Rev Dis Primers. 2020; 6(1):77. DOI: 10.1038/s41572-020-0209-6. View

15.

Auger J, Jouannet P, Eustache F . Another look at human sperm morphology. Hum Reprod. 2015; 31(1):10-23. DOI: 10.1093/humrep/dev251. View

16.

Lucas J, Davis S, Omran H, Shoemark A . Primary ciliary dyskinesia in the genomics age. Lancet Respir Med. 2019; 8(2):202-216. DOI: 10.1016/S2213-2600(19)30374-1. View

17.

Hannah W, Seifert B, Truty R, Zariwala M, Ameel K, Zhao Y . The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis. Lancet Respir Med. 2022; 10(5):459-468. PMC: 9064931. DOI: 10.1016/S2213-2600(21)00453-7. View

18.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J . 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(5):405-24. PMC: 4544753. DOI: 10.1038/gim.2015.30. View

19.

Kumar D, Rains A, Herranz-Perez V, Lu Q, Shi X, Swaney D . A ciliopathy complex builds distal appendages to initiate ciliogenesis. J Cell Biol. 2021; 220(9). PMC: 8276316. DOI: 10.1083/jcb.202011133. View

20.

Vieira J, Lopes P, Silva R . Primary ciliary dyskinesia and hydrocephalus with aqueductal stenosis. J Child Neurol. 2012; 27(7):938-41. DOI: 10.1177/0883073811429856. View