Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay
Combined complex deficiency

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Prevalence of clinical parameters (%)

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Pubmed id number as a reference Organ system affected
Number of patients in the reference Percent affected patients (Between 0 and 1, eg. 0.1 = 10%)
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List of symptoms

Symptom/sign Organ system Percent affected Pubmed id Added on(yyyy-mm-dd) Edit/add reference
Cataract nervous 100 % 19409522 2011-10-19
Hypotonia nervous 100 % 19409522 2011-10-11
Hearing loss nervous 100 % 19409522 2011-10-11
Developmental delay multi 100 % 19409522 2011-10-11
Ptosis nervous 66 % 19409522 2011-10-11
Lactate accumulation circulatory 66 % 19409522 2011-10-11
Areflexia nervous 33 % 19409522 2011-10-11
Nystagmus nervous 33 % 19409522 2011-10-11
Increased blood CK circulatory 33 % 19409522 2011-10-11

List of references:

The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency.
Alessio Di Fonzo, Dario Ronchi, Tiziana Lodi, Elisa Fassone, Marco Tigano, Costanza Lamperti, Stefania Corti, Andreina Bordoni, Francesco Fortunato, Monica Nizzardo, Laura Napoli, Chiara Donadoni, Sabrina Salani, Francesca Saladino, Maurizio Moggio, Nereo Bresolin, Iliana Ferrero, Giacomo P Comi,

A disulfide relay system (DRS) was recently identified in the yeast mitochondrial intermembrane space (IMS) that consists of two essential components: the sulfhydryl oxidase Erv1 and the redox-regulated import receptor Mia40. The DRS drives the import of cysteine-rich proteins into the IMS via an oxidative folding mechanism. Erv1p is reoxidized within this system, transferring its electrons to molecular oxygen through interactions with cytochrome c and cytochrome c oxidase (COX), thereby linking the DRS to the respiratory chain. The role of the human Erv1 ortholog, GFER, in the DRS has been poorly explored. Using homozygosity mapping, we discovered that a mutation in the GFER gene causes an infantile mitochondrial disorder. Three children born to healthy consanguineous parents presented with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. The consequences of the mutation at the level of the patient's muscle tissue and fibroblasts were 1) a reduction in complex I, II, and IV activity; 2) a lower cysteine-rich protein content; 3) abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and 4) accelerated time-dependent accumulation of multiple mtDNA deletions. Moreover, the Saccharomyces cerevisiae erv1(R182H) mutant strain reproduced the complex IV activity defect and exhibited genetic instability of the mtDNA and mitochondrial morphological defects. These findings shed light on the mechanisms of mitochondrial biogenesis, establish the role of GFER in the human DRS, and promote an understanding of the pathogenesis of a new mitochondrial disease.

American journal of human genetics - May 2009