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Cold Spring Harb Mol Case Stud. 2018 Aug 1;4(4). pii: a002998. doi: 10.1101/mcs.a002998. Print 2018 Aug.

De novo MYH9 mutation in congenital scalp hemangioma.

Author information

1
Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut 06519, USA.
2
Department of Genetics, Yale School of Medicine, New Haven, Connecticut 06519, USA.
3
Department of Pathology, Yale School of Medicine, New Haven, Connecticut 06519, USA.
4
Centers for Mendelian Genomics and Yale Program on Neurogenetics, Yale School of Medicine, New Haven, Connecticut 06519, USA.
5
Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut 06519, USA.
6
Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06519, USA.

Abstract

Congenital hemangiomas are tumor-like vascular malformations with poorly understood pathogenesis. We report the case of a neonate with a massive congenital scalp hemangioma that required urgent neurosurgical removal on the second day of life because of concern for high-flow arteriovenous shunting. Exome sequencing identified a rare damaging de novo germline mutation in MYH9 (c.5308C>T, p.[Arg1770Cys]), encoding the MYH9 nonmuscle myosin IIA. MYH9 has a probability of loss-of-function intolerance (pLI) score of >0.99 and is highly intolerant to missense variation (z score = 5.59). The p.(Arg1770Cys) mutation substitutes an evolutionarily conserved amino acid in the protein's critical myosin tail domain and is predicted to be highly deleterious by SIFT, PolyPhen-2, MetaSVM, and CADD. MYH9 is a known regulator of cytokinesis, VEGF-regulated angiogenesis, and p53-dependent tumorigenesis. These findings reveal a novel association of germline de novo MYH9 mutation with congenital hemangioma.

KEYWORDS:

hemangioma

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