Details

Autor(en) / Beteiligte

• Hidalgo Mayoral, Irene
• Martínez-Salio, Antonio
• Llamas-Velasco, Sara
• Gómez-Majón, Irene
• Arteche-López, Ana
• Quesada-Espinosa, Juan Francisco
• Milla, Carmen Palma
• Lezana Rosales, Jose Miguel
• Pérez de la Fuente, Rubén
• Rufián, Alexandra Juárez
• Tomillo, Olalla Sierra
• Sánchez Calvín, Maria Teresa
• Gómez Rodríguez, Maria José
• Gómez, Patricia Ramos
• Villarejo-Galende, Alberto
• Díaz-Guzmán, Jaime
• Ortega-Casarrubios, Maria Ángeles
• Calleja-Castaño, Patricia
• Moreno-García, Marta

Titel

Hereditary cerebral small vessel disease: Assessment of a HTRA1 variant using protein stability predictors and 3D modelling

Ist Teil von

• European journal of medical genetics, 2022-08, Vol.65 (8), p.104539-104539, Article 104539

Ort / Verlag

Netherlands: Elsevier Masson SAS

Erscheinungsjahr

2022

Quelle

ScienceDirect

Beschreibungen/Notizen

• Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive vascular disorder caused by biallellic variants in HTRA1. Recently, it has been reported that several heterozygous mutations in HTRA1 are responsible for a milder late-onset cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. The majority of them are missense that affects the Htr1A protease activity due to a dominant-negative effect caused by defective trimerization or monomer activation. The molecular mechanism related to the structural destabilization of the protein supports the practical utility of integrating computational stability predictors to prioritize candidate variants in this gene. In this work, we report a family with several members diagnosed with subcortical ischemic events and progressive cognitive impairment caused by the novel c.820C > G, p.(Arg274Gly) heterozygous variant in HTRA1 segregating in an autosomal dominant manner and propose its molecular mechanism by a three-dimensional model of the protein's structure.