Recurrent p.H119Y variant in MAP2K1 expands the phenotypic spectrum of MAP2K1 -related RASopathy.

Autor: Grange DK; Edward Mallinckrodt Department of Pediatrics, Washington University in St. Louis, St. Louis, Missouri, USA., Wegner DJ; Edward Mallinckrodt Department of Pediatrics, Washington University in St. Louis, St. Louis, Missouri, USA., Wambach JA; Edward Mallinckrodt Department of Pediatrics, Washington University in St. Louis, St. Louis, Missouri, USA., Sisco KA; Edward Mallinckrodt Department of Pediatrics, Washington University in St. Louis, St. Louis, Missouri, USA., Stone SI; Edward Mallinckrodt Department of Pediatrics, Washington University in St. Louis, St. Louis, Missouri, USA., Sheehan JH; John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Ramsey KM; Center for Rare Childhood Disorders, Translational Genomics Research Institute, Phoenix, Arizona, USA., Narayanan V; Center for Rare Childhood Disorders, Translational Genomics Research Institute, Phoenix, Arizona, USA., Rauen KA; Department of Pediatrics, University of California Davis, Sacramento, California, USA., Cole FS; Edward Mallinckrodt Department of Pediatrics, Washington University in St. Louis, St. Louis, Missouri, USA.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2025 Jan; Vol. 197 (1), pp. e63854. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1002/ajmg.a.63854
Abstrakt: We report three unrelated individuals with atypical clinical findings for cardio-facio-cutaneous (CFC) syndrome, all of whom have the same novel, heterozygous de novo p.H119Y (c.355 C>T) transition variant in MAP2K1, identified by exome sequencing. MAP2K1 encodes MEK1, dual specificity mitogen-activated protein kinase kinase 1, and is one of four genes in the canonical RAS/MAPK signal transduction pathway associated with CFC syndrome. The p.H119Y variant is a non-conservative amino acid substitution that is predicted to impact the tertiary protein structure, and it occurs at a position in the protein kinase domain of MAP2K1 that is highly conserved across species. The clinical findings in these three individuals include facial features that are nonclassical for CFC syndrome, extremely poor weight gain, absence of congenital cardiac defects or cardiomyopathy, normal cognition or only mild intellectual disabilities, normal hair, mild skin abnormalities, and consistent behavioral features of anxiety, photophobia, and sensory hypersensitivities. These individuals expand the phenotypic spectrum of MAP2K1-related RASopathy.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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