Back to Search
Start Over
EVEN-PLUS syndrome: A case report with novel variants in HSPA9 and evidence of HSPA9 gene dysfunction.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2020 Nov; Vol. 182 (11), pp. 2501-2507. Date of Electronic Publication: 2020 Sep 01. - Publication Year :
- 2020
-
Abstract
- EVEN-PLUS syndrome is a rare condition characterized by its involvement of the Epiphyses, Vertebrae, Ears, and Nose, PLUS other associated findings. We report here the fifth case of EVEN-PLUS syndrome with novel variants c.818 T > G (p.L273X) and c.955C > T (p.L319F) in the HSPA9 gene identified through whole-exome sequencing. The patient is the first male known to be affected and presented with additional features not previously described with EVEN-PLUS syndrome. These features include agenesis of the septum pellucidum, a short chest and sternum, 13 pairs of ribs, a single hemivertebra, laterally displaced nipples, hydronephrosis, unilateral cryptorchidism, unilateral single palmar crease, bilateral clubfoot, and hypotonia. qPCR analysis provides supporting evidence for a nonsense-mediated decay mechanism for the HSPA9 truncating variant. In silico 3D modeling supports the pathogenicity of the c.955C > T (p.L319F) missense variant. The study presented here further describes the syndrome and broadens its mutational and phenotypic spectrum. Our study also lends support to HSPA9 variants as the underlying etiology of EVEN-PLUS syndrome and ultimately provides a better understanding of the molecular basis of the condition.<br /> (© 2020 Wiley Periodicals LLC.)
- Subjects :
- Clubfoot complications
Cryptorchidism complications
Exome
Genetic Association Studies
Genetic Variation
Humans
Hydronephrosis complications
Imaging, Three-Dimensional
Infant
Karyotyping
Male
Muscle Hypotonia complications
Mutation
Phenotype
RNA, Messenger metabolism
Ribs abnormalities
Septum Pellucidum abnormalities
Sternum abnormalities
Syndrome
Exome Sequencing
HSP70 Heat-Shock Proteins genetics
Mitochondrial Proteins genetics
Musculoskeletal Abnormalities genetics
Mutation, Missense
Septum Pellucidum pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4833
- Volume :
- 182
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 32869452
- Full Text :
- https://doi.org/10.1002/ajmg.a.61808