Title |
FBXO32, encoding a member of the SCF complex, is mutated in dilated cardiomyopathy
|
---|---|
Published in |
Genome Biology, January 2016
|
DOI | 10.1186/s13059-015-0861-4 |
Pubmed ID | |
Authors |
Nadya Al-Yacoub, Ranad Shaheen, Salma Mahmoud Awad, Muhammad Kunhi, Nduna Dzimiri, Henry C. Nguyen, Yong Xiong, Jehad Al-Buraiki, Waleed Al-Habeeb, Fowzan S. Alkuraya, Coralie Poizat |
Abstract |
Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy causing systolic dysfunction and heart failure. Rare variants in more than 30 genes, mostly encoding sarcomeric proteins and proteins of the cytoskeleton, have been implicated in familial DCM to date. Yet, the majority of variants causing DCM remain to be identified. The goal of the study is to identify novel mutations causing familial dilated cardiomyopathy. We identify FBXO32 (ATROGIN 1), a member of the F-Box protein family, as a novel DCM-causing locus. The missense mutation affects a highly conserved amino acid and is predicted to severely impair binding to SCF proteins. This is validated by co-immunoprecipitation experiments from cells expressing the mutant protein and from human heart tissue from two of the affected patients. We also demonstrate that the hearts of the patients with the FBXO32 mutation show accumulation of selected proteins regulating autophagy. Our results indicate that abnormal SCF activity with subsequent impairment of the autophagic flux due to a novel FBXO32 mutation is implicated in the pathogenesis of DCM. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Saudi Arabia | 55 | 42% |
United Kingdom | 3 | 2% |
Bahrain | 2 | 2% |
Germany | 2 | 2% |
Canada | 1 | <1% |
Turkey | 1 | <1% |
Malaysia | 1 | <1% |
Jordan | 1 | <1% |
Netherlands | 1 | <1% |
Other | 2 | 2% |
Unknown | 61 | 47% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 111 | 85% |
Practitioners (doctors, other healthcare professionals) | 8 | 6% |
Scientists | 8 | 6% |
Science communicators (journalists, bloggers, editors) | 3 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 35 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 5 | 14% |
Student > Bachelor | 5 | 14% |
Researcher | 3 | 9% |
Student > Postgraduate | 3 | 9% |
Student > Master | 3 | 9% |
Other | 6 | 17% |
Unknown | 10 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 9 | 26% |
Agricultural and Biological Sciences | 5 | 14% |
Medicine and Dentistry | 4 | 11% |
Computer Science | 1 | 3% |
Nursing and Health Professions | 1 | 3% |
Other | 2 | 6% |
Unknown | 13 | 37% |