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. 2024 Mar;17(3):e011226.
doi: 10.1161/CIRCHEARTFAILURE.123.011226. Epub 2024 Mar 4.

Biallelic Loss of Function Variants in Myocardial Zonula Adherens Protein Gene (MYZAP) Cause a Severe Recessive Form of Dilated Cardiomyopathy

Juan Pablo Ochoa  1   2   3 , Laura Lalaguna  3 , Jesús G Mirelis  1 , Fernando Dominguez  1   2   3 , Esther Gonzalez-Lopez  1   2   3 , Clara Salas  1   2 , Gaston Roustan  1 , Kathryn A McGurk  4   5 , Sean L Zheng  4   5   6 , Paul J R Barton  4   5   6 , James S Ware  4   5   6 , María Victoria Gómez-Gaviro  7   8 , Enrique Lara-Pezzi  2   3 , Pablo Garcia-Pavia  1   2   3   9
Affiliations

Biallelic Loss of Function Variants in Myocardial Zonula Adherens Protein Gene (MYZAP) Cause a Severe Recessive Form of Dilated Cardiomyopathy

Juan Pablo Ochoa et al. Circ Heart Fail. 2024 Mar.
No abstract available

Keywords: cardiomyopathies; dilated cardiomyopathy; human genetics; tachycardia, ventricular; whole exome sequencing.

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Conflict of interest statement

Dr Ochoa is an employee of Health in Code. Dr Ware has consulted for MyoKardia Inc, Foresite Labs, and Pfizer. The other authors reports no conflicts.

Figures

Figure.
Figure.
Clinical and functional evaluations performed in the family. A, Family pedigree and cardiac magnetic resonance imaging of the index case (upper) showing LV dilatation (LVEDV=168 mL) and extensive areas of midventricular fibrosis predominantly in the left ventricle. Her affected sister (lower) had similar findings on magnetic resonance imaging (LVEDV=260 mL). B, MYZAP immunostaining in skin samples from affected siblings and unaffected parents. Skin biopsies were immunostained with anti-MYZAP antibody (white). Nuclei were stained with DAPI (blue). Images were acquired with a 20× objective. Magnifications of the selected areas (yellow squares) were acquired with a 40× objective. C, Western blot analysis of MYZAP in HL-1 cells transfected with MYZAP-WT, MYZAP-p.Arg117*, and MYZAP-c.933+1G>A. MYZAP-c.933+1G>A shows significantly lower expression level of MYZAP compared with MYZAP-WT and MYZAP-p.Arg117*. D, Immunofluorescence analysis of localization of MYZAP in transfected HL-1 cells showing that MYZAP-WT and MYZAP-c.933+1G>A are observed predominantly as perinuclear aggregations and in the cytoplasmatic membrane, while MYZAP-p.Arg117* delocalizes being distributed in the cytoplasm but not in any particular structure at cell level. Bar, 20 µm. DAPI indicates 4′,6-diamidino-2-phenylindole; LVEDV, left ventricle end diastolic volume; VINC, vinculin; and WT, wild-type.
See this image and copyright information in PMC

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