De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy

被引：144

作者：

Klauke, Baerbel ^{[1
,2
]}

Kossmann, Sabine ^{[1
,2
]}

Gaertner, Anna ^{[1
,2
]}

Brand, Kristina ^{[1
,2
]}

Stork, Ines ^{[1
,2
]}

Brodehl, Andreas ^{[1
,2
]}

Dieding, Mareike ^{[3
]}

Walhorn, Volker ^{[3
]}

Anselmetti, Dario ^{[3
]}

Gerdes, Desiree ^{[1
,2
]}

Bohms, Birte ^{[1
,2
]}

Schulz, Uwe ^{[1
,2
]}

Knyphausen, Edzard Zu ^{[1
,2
]}

Vorgerd, Matthias ^{[4
]}

Gummert, Jan ^{[1
,2
]}

Milting, Hendrik ^{[1
,2
]}

机构：

[1] Ruhr Univ Bochum, Herz & Diabet Zentrum NRW, Univ Klinikum,Klin F Thorax & Kardiovaskularchiru, E&H Klessmann Inst Kardiovaskulaere Forsch & Entw, D-32545 Bad Oeynhausen, Germany

[2] Klin Angeborene Herzfehler, D-32545 Bad Oeynhausen, Germany

[3] Univ Bielefeld, Fak Phys, D-33615 Bielefeld, Germany

[4] Univ Klinikum Bergmannsheil, Neurol Klin & Poliklin, D-44789 Bochum, Germany

来源：

HUMAN MOLECULAR GENETICS | 2010年 / 19卷 / 23期

关键词：

INTERMEDIATE-FILAMENT PROTEINS; WOOLLY HAIR; DILATED CARDIOMYOPATHY; PALMOPLANTAR KERATODERMA; RECESSIVE MUTATION; SKELETAL MYOPATHY; DISEASE; GENE; DYSPLASIA/CARDIOMYOPATHY; DESMOCOLLIN-2;

D O I：

10.1093/hmg/ddq387

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease, frequently accompanied by sudden cardiac death and terminal heart failure. Genotyping of ARVC patients might be used for palliative treatment of the affected family. We genotyped a cohort of 22 ARVC patients referred to molecular genetic screening in our heart center for mutations in the desmosomal candidate genes JUP, DSG2, DSC2, DSP and PKP2 known to be associated with ARVC. In 43% of the cohort, we found disease-associated sequence variants. In addition, we screened for desmin mutations and found a novel desmin-mutation p. N116S in a patient with ARVC and terminal heart failure, which is located in segment 1A of the desmin rod domain. The mutation leads to the aggresome formation in cardiac and skeletal muscle without signs of an overt clinical myopathy. Cardiac aggresomes appear to be prominent, especially in the right ventricle of the heart. Viscosimetry and atomic force microscopy of the desmin wild-type and N116S mutant isolated from recombinant Escherichia coli revealed severe impairment of the filament formation, which was supported by transfections in SW13 cells. Thus, the gene coding for desmin appears to be a novel ARVC gene, which should be included in molecular genetic screening of ARVC patients.

引用

页码：4595 / 4607

页数：13

共 56 条

[1] A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair [J].