Broadening the phenotypic spectrum of EVEN-PLUS syndrome through identification of HSPA9 pathogenic variants in the original EVE dysplasia family and two sibs with milder facial phenotype.
CODAS syndrome
EVE dysplasia
EVEN-PLUS syndrome
HSPA9
anorectal malformation
aplasia cutis
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:
09 2022
09 2022
Historique:
revised:
25
05
2022
received:
05
10
2021
accepted:
13
06
2022
pubmed:
3
7
2022
medline:
17
8
2022
entrez:
2
7
2022
Statut:
ppublish
Résumé
EVEN-PLUS syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the mitochondrial chaperone called mortalin, encoded by HSPA9. This genetic disorder, presenting with several overlapping features with CODAS syndrome, is characterized by the involvement of the Epiphyses, Vertebrae, Ears, and Nose (EVEN), PLUS associated findings. Only five individuals presenting with the EVEN-PLUS phenotype and biallelic variants in HSPA9 have been published. Here, we expand the phenotypic and molecular spectrum associated with this disorder, reporting two sibs with a milder phenotype and compound heterozygous pathogenic variants (a recurrent variant and a novel one). Also, we confirm a homozygous pathogenic variant in the family originally reported as EVE dysplasia.
Identifiants
pubmed: 35779070
doi: 10.1002/ajmg.a.62883
doi:
Substances chimiques
HSP70 Heat-Shock Proteins
0
HSPA9 protein, human
0
Mitochondrial Proteins
0
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2819-2824Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
Amiel, J., Cormier-Daire, V., Journeau, P., Mussat, P., Munnich, A., & Lyonnet, S. (1999). Epiphyseal, vertebral, and ear (EVE) dysplasia: A new syndrome? Journal of Medical Genetics, 36(7), 561-564. https://doi.org/10.1136/jmg.36.7.561
Moseng, M. A., Nix, J. C., & Page, R. C. (2019). Biophysical consequences of EVEN-PLUS syndrome mutations for the function of mortalin. Journal of Physical Chemistry B, 123(16), 3383-3396. https://doi.org/10.1021/acs.jpcb.9b00071
Nagrani, D. G., Kurniawan, A., Wahyuni, L. K., Xavier, B. C., Furga, A. S., & Sjarif, D. R. (2018). Postural and gait abnormality in Even-Plus syndrome. Journal of Molecular and Genetic Medicine, 12(2), 1-5. https://doi.org/10.4172/1747-0862.1000350
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., & Rehm, H. L. (2015). 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. Genetics in Medicine, 17(5), 405-424. https://doi.org/10.1038/gim.2015.30
Royer-Bertrand, B., Castillo-Taucher, S., Moreno-Salinas, R., Cho, T.-J., Chae, J.-H., Choi, M., Kim, O. H., Dikoglu, E., Campos-Xavier, B., Girardi, E., Superti-Furga, G., Bonafé, L., Rivolta, C., Unger, S., & Superti-Furga, A. (2015). Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia. Scientific Reports, 5, 17154. https://doi.org/10.1038/srep17154
Younger, G., Vetrini, F., Weaver, D. D., Lynnes, T. C., Treat, K., Pratt, V. M., & Torres-Martinez, W. (2020). EVEN-PLUS syndrome: A case report with novel variants in HSPA9 and evidence of HSPA9 gene dysfunction. American Journal of Medical Genetics, Part A, 182(11), 2501-2507. https://doi.org/10.1002/ajmg.a.61808