Genetics of 67 patients of suspected primary ciliary dyskinesia from India.
Kartagener syndrome
mutation
primary ciliary dyskinesia
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
14 Jul 2024
14 Jul 2024
Historique:
revised:
27
06
2024
received:
25
03
2024
accepted:
03
07
2024
medline:
15
7
2024
pubmed:
15
7
2024
entrez:
15
7
2024
Statut:
aheadofprint
Résumé
Data are limited on the genetic profile of primary ciliary dyskinesia (PCD) from developing countries. Here, we report one of the first study on genetic profile of patients with suspected PCD from India. In this prospective cross-sectional study, we enrolled 162 children with suspected PCD. We recorded clinical features, relevant laboratory tests for PCD and performed whole exome sequencing (WES). We are reporting 67 patients here who had positive variant/s on WES. We had 117 variants in 40 genes among 67 patients. Among the 108 unique variants, 33 were categorized as pathogenic or likely pathogenic (P/LP). We had nine novel variants in out cohort. The 29 definite PCD cases, diagnosed by composite reference standards, had variants in 16 genes namely LRRC6/DNAAF11 (5), DNAH5 (3), CCDC39 (3), HYDIN (3), DNAH11 (2), CCDC40 (2), CCDC65 (2) and one each DNAAF3, DNAAF2, CFAP300, RPGR, CCDC103, CCDC114, SPAG1, DNAI1, and DNAH14. To conclude, we identified 108 unique variants in 40 genes among 67 patients. The common genes involved in definite cases of PCD in Indian patients were LRRC6, DNAH5, CCDC39, and HYDIN. Our findings suggest a need to develop a separate genetic panel for PCD in the Indian population.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Indian Council of Medical Research
ID : 5/7/1583/2017-RCH
Organisme : Department of Biotechnology, Ministry of Science and Technology, India
ID : BT/PR26396/MED/12/790/2017
Informations de copyright
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Popatia R, Haver K, Casey A. Primary ciliary dyskinesia: an update on new diagnostic modalities and review of the literature. Pediatr Allergy Immunol Pulmonol. 2014;27:51‐59.
Hannah WB, Seifert BA, Truty R, et al. The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis. Lancet Respir Med. 2022;10:459‐468.
Lucas JS, Davis SD, Omran H, Shoemark A. Primary ciliary dyskinesia in the genomics age. Lancet Respir Med. 2020;8:202‐216.
Behan L, Dimitrov BD, Kuehni CE, et al. PICADAR: a diagnostic predictive tool for primary ciliary dyskinesia. Eur Respir J. 2016;47:1103‐1112.
Marthin JK, Nielsen KG. Hand‐held tidal breathing nasal nitric oxide measurement—a promising targeted case‐finding tool for the diagnosis of primary ciliary dyskinesia. PLoS One. 2013;8:e57262.
Leigh MW, Ferkol TW, Davis SD, et al. Clinical features and associated likelihood of primary ciliary dyskinesia in children and adolescents. Ann Am Thorac Soc. 2016;13:1305‐1313.
Werner C, Lablans M, Ataian M, et al. An international registry for primary ciliary dyskinesia. Eur Respir J. 2016;47:849‐859.
Shoemark A, Boon M, Brochhausen C, et al. International consensus guideline for reporting transmission electron microscopy results in the diagnosis of primary ciliary dyskinesia (BEAT PCD TEM criteria). Eur Respir J. 2020;55:1900725.
Boaretto F, Snijders D, Salvoro C, et al. Diagnosis of primary ciliary dyskinesia by a targeted next‐generation sequencing panel: molecular and clinical findings in Italian patients. J Mol Diagn. 2016;18:912‐922.
Kim RH, Hall DA, Cutz E, et al. The role of molecular genetic analysis in the diagnosis of primary ciliary dyskinesia. Ann Am Thorac Soc. 2014;11:351‐359.
Sehgal IS, Dhooria S, Bal A, et al. A young girl with bronchiectasis and elevated sweat chloride. Chest. 2021;159:e155‐e158.
Benjamin AT, Ganesh R, Gaspar BL, et al. A novel homozygous nonsense HYDIN gene mutation p.(Arg951*) in primary ciliary dyskinesia. Indian J Pediatr. 2019;86:664‐665.
Benjamin AT, Ganesh R, Chinnappa J, Kinimi I, Lucas J. Primary ciliary dyskinesia due to DRC1/CCDC164 gene mutation. Lung India. 2020;37:179‐180.
Shoemark A, Moya E, Hirst RA, et al. High prevalence of CCDC103 p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations. Thorax. 2018;73:157‐166.
Shapiro AJ, Davis SD, Polineni D, et al. Diagnosis of primary ciliary dyskinesia. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2018;197:e24‐e39.