Interfamilial clinical variability in four Polish families with cranioectodermal dysplasia and identical compound heterozygous variants in WDR35.
Bone and Bones
/ abnormalities
Child
Child, Preschool
Cilia
/ genetics
Craniosynostoses
/ epidemiology
Cytoskeletal Proteins
/ genetics
Ectodermal Dysplasia
/ epidemiology
Female
Humans
Infant
Intracellular Signaling Peptides and Proteins
/ genetics
Male
Mutation
/ genetics
Pedigree
Phenotype
Poland
/ epidemiology
Ciliopathy
Sensenbrenner syndrome
WDR35
clinical variability, renal failure
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
02
12
2020
received:
23
09
2020
accepted:
24
12
2020
pubmed:
10
1
2021
medline:
4
8
2021
entrez:
9
1
2021
Statut:
ppublish
Résumé
Cranioectodermal dysplasia (CED) is a rare autosomal recessive disorder primarily characterized by craniofacial, skeletal, and ectodermal abnormalities. CED is a chondrodysplasia, which is part of a spectrum of clinically and genetically heterogeneous diseases that result from disruptions in cilia. Pathogenic variants in genes encoding components of the ciliary transport machinery are known to cause CED. Intra- and interfamilial clinical variability has been reported in a few CED studies and the findings of this study align with these observations. Here, we report on five CED patients from four Polish families with identical compound heterozygous variants [c.1922T>G p.(Leu641Ter) and c.2522A>T; p.(Asp841Val)] in WDR35. The frequent occurrence of both identified changes in Polish CED families suggests that these variants may be founder mutations. Clinical evaluation of the CED patients revealed interfamilial clinical variability among the patients. This includes differences in skeletal and ectodermal features as well as variability in development, progression, and severity of renal and liver insufficiency. This is the first report showing significant interfamilial clinical variability in a series of CED patients from unrelated families with identical compound heterozygous variants in WDR35. Our findings strongly indicate that other genetic and non-genetic factors may modulate the progression and expression of the patients' phenotypes.
Identifiants
pubmed: 33421337
doi: 10.1002/ajmg.a.62067
doi:
Substances chimiques
Cytoskeletal Proteins
0
Intracellular Signaling Peptides and Proteins
0
WDR35 protein, human
0
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1195-1203Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Al-Salem, A. H. (2017). Inguinal hernias and hydroceles. In An illustrated guide to pediatric urology (pp. 401-414). Cham: Springer. https://doi.org/10.1007/978-3-319-44182-5_17.
Antony, D., Nampoory, N., Bacchellie, C., Melhem, M., Wu, K., James, C. T., … Alsmadi, O. (2017). Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: Example of a WDR35 mutation case and review of the literature. European Journal of Medical Genetics, 60(12), 658-666. https://doi.org/10.1016/j.ejmg.2017.08.019
Arts, H., & Knoers, N. (1993). Cranioectodermal dysplasia. In Genereviews®. Seattle (WA): University of Washington. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24027799
Bacino, C. A., Dhar, S. U., Brunetti-Pierri, N., Lee, B., & Bonnen, P. E. (2012). WDR35 mutation in siblings with Sensenbrenner syndrome: A ciliopathy with variable phenotype. American Journal of Medical Genetics Part A, 158A(11), 2917-2924. https://doi.org/10.1002/ajmg.a.35608
Caparrós-Martín, J. A., De Luca, A., Cartault, F., Aglan, M., Temtamy, S., Otaify, G. A., … Ruiz-Perez, V. L. (2015). Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium. Human Molecular Genetics, 24(14), 4126-4137. https://doi.org/10.1093/hmg/ddv152
Córdova-Fletes, C., Becerra-Solano, L. E., Rangel-Sosa, M. M., Rivas-Estilla, A. M., Alberto Galán-Huerta, K., Ortiz-López, R., … García-Ortiz, J. E. (2018). Uncommon runs of homozygosity disclose homozygous missense mutations in two ciliopathy-related genes ( SPAG17 and WDR35 ) in a patient with multiple brain and skeletal anomalies. European Journal of Medical Genetics, 61(3), 161-167. https://doi.org/10.1016/j.ejmg.2017.11.011
Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P., … Brunner, H. G. (2010). Exome Sequencing Identifies WDR35 Variants Involved in Sensenbrenner Syndrome. The American Journal of Human Genetics, 87(3), 418-423. http://dx.doi.org/10.1016/j.ajhg.2010.08.004.
Hoffer, J., Fryssira, H., Konstantinidou, A., Ropers, H., & Tzschach, A. (2013). Novel WDR35 mutations in patients with cranioectodermal dysplasia (Sensenbrenner syndrome). Clinical Genetics, 83(1), 92-95. https://doi.org/10.1111/j.1399-0004.2012.01880.x
Li, Y., Garrod, A. S., Madan-Khetarpal, S., Sreedher, G., McGuire, M., Yagi, H., … Lo, C. W. (2015). Respiratory motile cilia dysfunction in a patient with cranioectodermal dysplasia. American Journal of Medical Genetics Part A, 167(9), 2188-2196. https://doi.org/10.1002/ajmg.a.37133
Lin, A. E., Traum, A. Z., Sahai, I., Keppler-Noreuil, K., Kukolich, M. K., Adam, M. P., … Arts, H. H. (2013). Sensenbrenner syndrome (Cranioectodermal dysplasia): Clinical and molecular analyses of 39 patients including two new patients. American Journal of Medical Genetics Part A, 161(11), 2762-2776. https://doi.org/10.1002/ajmg.a.36265
Mill, P., Lockhart, P. J., Fitzpatrick, E., Mountford, H. S., Hall, E. A., Reijns, M. A. M., … Amor, D. J. (2011). Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis. American Journal of Human Genetics, 88(4), 508-515. https://doi.org/10.1016/J.AJHG.2011.03.015
Mitchison, H. M., & Valente, E. M. (2017). Motile and non-motile cilia in human pathology: From function to phenotypes. The Journal of Pathology, 241(2), 294-309. https://doi.org/10.1002/path.4843
Oud, M., Lamers, I., & Arts, H. (2017). Ciliopathies: Genetics in pediatric medicine. Journal of Pediatric Genetics, 06(01), 18-29. https://doi.org/10.1055/s-0036-1593841
Pazour, G. J., Quarmby, L., Smith, A. O., Desai, P. B., & Schmidts, M. (2020). Cilia in cystic kidney and other diseases. Cellular Signalling, 69, 109519. https://doi.org/10.1016/J.CELLSIG.2019.109519
Schmidts, M., & Mitchison, H. M. (2018). Severe skeletal abnormalities caused by defects in retrograde intraflagellar transport dyneins. In S. M. King (Ed.), Dyneins: Structure, Biology and Disease. (Vol. 2, pp. 356-401). Cambridge, MA: Academic Press. https://doi.org/10.1016/B978-0-12-809470-9.00015-1.
Shaheen, R., Szymanska, K., Basu, B., Patel, N., Ewida, N., Faqeih, E., … Alkuraya, F. S. (2016). Characterizing the morbid genome of ciliopathies. Genome Biology, 17(1), 242. https://doi.org/10.1186/s13059-016-1099-5
Walczak-Sztulpa, J., Wawrocka, A., Leszczynska, B., Mikulska, B., Arts, H. H., Bukowska-Olech, E., … Obersztyn, E. (2020). Prenatal genetic diagnosis of cranioectodermal dysplasia in a polish family with compound heterozygous variants in WDR35. American Journal of Medical Genetics. Part A., 182, 2417-2425. https://doi.org/10.1002/ajmg.a.61785
Walczak-Sztulpa, J., Wawrocka, A., Sobierajewicz, A., Kuszel, L., Zawadzki, J., Grenda, R., … Chrzanowska, K. H. (2017). Intrafamilial phenotypic variability in a polish family with Sensenbrenner syndrome and biallelic WDR35 mutations. American Journal of Medical Genetics Part A, 173(5), 1364-1368. https://doi.org/10.1002/ajmg.a.38163
Walczak-Sztulpa, J., Wawrocka, A., Swiader-Lesniak, A., Socha, M., Jamsheer, A., Drozdz, D., … Zachwieja, K. (2018). Clinical and molecular genetic characterization of a male patient with Sensenbrenner syndrome (cranioectodermal dysplasia) and biallelic WDR35 mutations. Birth Defects Research, 110(4), 376-381. https://doi.org/10.1002/bdr2.1151
Wheway, G., Mitchison, H. M., Mitchison, H. M., Ambrose, J. C., Baple, E. L., Bleda, M., … Zarowiecki, M. (2019). Opportunities and challenges for molecular understanding of Ciliopathies-the 100,000 genomes project. Frontiers in Genetics, 10, 127. https://doi.org/10.3389/fgene.2019.00127
Zaki, M. S., Sattar, S., Massoudi, R. A., & Gleeson, J. G. (2011). Co-occurrence of distinct ciliopathy diseases in single families suggests genetic modifiers. American Journal of Medical Genetics. Part A, 155A(12), 3042-3049. https://doi.org/10.1002/ajmg.a.34173