Noonan syndrome-like phenotype associated with an ERF frameshift variant.

Autor: Hirano Y; Department of Pediatrics, Hiratsuka City Hospital, Hiratsuka, Kanagawa, Japan.; Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan., Kuroda Y; Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan., Enomoto Y; Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Japan., Naruto T; Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Japan., Muroya K; Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan., Kurosawa K; Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2024 Sep; Vol. 194 (9), pp. e63652. Date of Electronic Publication: 2024 May 14.
DOI: 10.1002/ajmg.a.63652
Abstrakt: Noonan syndrome is a so-called "RASopathy," that is characterized by short stature, distinctive facial features, congenital heart defects, and developmental delay. Of individuals with a clinical diagnosis of Noonan syndrome, 80%-90% have pathogenic variants in the known genes implicated in the disorder, but the molecular mechanism is unknown in the remaining cases. Heterozygous pathogenic variants of ETS2 repressor factor (ERF), which functions as a repressor in the RAS/MAPK signaling pathway, cause syndromic craniosynostosis. Here, we report an ERF frameshift variant cosegregating with a Noonan syndrome-like phenotype in a family. The proband was a 3-year-old female who presented with dysmorphic facial features, including proptosis, hypertelorism, slightly down slanted palpebral fissures, low-set posteriorly rotated ears, depressed nasal bridge, short stature, and developmental delay. Exome sequencing of the proband identified a heterozygous ERF variant [NM_006494.4: c.185del p.(Glu62Glyfs*15)]. Her mother and sister showed a similar phenotype and had the same heterozygous ERF variant. A large proportion of the previously reported patients with syndromic craniosynostosis and pathogenic ERF variants also showed characteristic features that overlap with those of Noonan syndrome. The present finding supports an association between heterozygous ERF variants and a Noonan syndrome-like phenotype.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: