Mitochondrial DNA deletion syndrome with progressive myopathy

General Information (adopted from Orphanet):

Synonyms, Signs: PEOA6
Progressive external ophthalmoplegia, autosomal dominant, 6
mtDNA deletion syndrome with progressive myopathy
mtDNA deletion syndrome with limb-girdle weakness
Mitochondrial DNA deletion syndrome with limb-girdle weakness
Number of Symptoms 28
OrphanetNr: 352470
OMIM Id: 615156
ICD-10: G71.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 0.1 of 100 000 [Orphanet]
Inheritance: Autosomal dominant
23352259 [IBIS]
Age of onset: Childhood
Adult
23352259 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial myopathy
 -Rare genetic disease
 -Rare neurologic disease
Multiple mitochondrial DNA deletion syndrome
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

DNA2 encodes a helicase/nuclease family member that is most likely involved in mtDNA replication, as well as in the long-patch base-excision repair (LP-BER) pathway. Mutations in DNA2 link progressive myopathy to mitochondrial DNA instability and are associated with autosomal dominant progressive external ophthalmoplegia-6 (PEOA6) (PMID:23352259).

Symptom Information: Sort by abundance 

1
 (HPO:0000544) External ophthalmoplegia Very frequent [IBIS] 23352259 IBIS 40 / 7739
2
 (HPO:0000597) Ophthalmoparesis 23352259 IBIS 71 / 7739
3
 (HPO:0000602) Ophthalmoplegia 23352259 IBIS 56 / 7739
4
 (HPO:0000651) Diplopia 23352259 IBIS 37 / 7739
5
 (HPO:0000508) Ptosis Frequent [IBIS] 23352259 IBIS 459 / 7739
6
 (HPO:0002875) Exertional dyspnea 23352259 IBIS 29 / 7739
7
 (HPO:0001533) Slender build 23352259 IBIS 11 / 7739
8
 (HPO:0001655) Patent foramen ovale 23352259 IBIS 31 / 7739
9
 (HPO:0003236) Elevated serum creatine phosphokinase 23352259 IBIS 214 / 7739
10
 (HPO:0010628) Facial palsy 23352259 IBIS 146 / 7739
11
 (HPO:0100295) Muscle fiber atrophy 23352259 IBIS 22 / 7739
12
 (HPO:0003200) Ragged-red muscle fibers 23352259 IBIS 37 / 7739
13
 (HPO:0003202) Skeletal muscle atrophy 23352259 IBIS 281 / 7739
14
 (HPO:0003700) Generalized amyotrophy 23352259 IBIS 39 / 7739
15
 (HPO:0001252) Muscular hypotonia 23352259 IBIS 990 / 7739
16
 (HPO:0003394) Muscle cramps 23352259 IBIS 106 / 7739
17
 (HPO:0007340) Lower limb muscle weakness 23352259 IBIS 61 / 7739
18
 (HPO:0003325) Limb-girdle muscle weakness 23352259 IBIS 22 / 7739
19
 (HPO:0003391) Gowers sign 23352259 IBIS 37 / 7739
20
 (HPO:0003326) Myalgia 23352259 IBIS 143 / 7739
21
 (HPO:0000716) Depression 23352259 IBIS 99 / 7739
22
 (HPO:0002870) Obstructive sleep apnea 23352259 IBIS 16 / 7739
23
 (HPO:0001288) Gait disturbance 23352259 IBIS 318 / 7739
24
 (HPO:0002938) Lumbar hyperlordosis 23352259 IBIS 73 / 7739
25
 (HPO:0000836) Hyperthyroidism 23352259 IBIS 25 / 7739
26
 (HPO:0003688) Decreased activity of cytochrome C oxidase in muscle tissue 23352259 IBIS 20 / 7739
27
 (HPO:0003689) Multiple mitochondrial DNA deletions 23352259 IBIS 12 / 7739
28
 (HPO:0003737) Mitochondrial myopathy 23352259 IBIS 18 / 7739

Associated genes:

DNA2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) PEOA6 is characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA (mtDNA) deletions on muscle biopsy. Symptoms may appear in childhood or adulthood and show slow progression (summary by Ronchi et ...
Clinical Description OMIM Ronchi et al. (2013) reported 2 sibs and 2 unrelated patients with PEOA6. One of the sibs reported declining muscle strength since young adulthood. At age 49 years, he was diagnosed with a suspected myopathy. Examination at age ...
Molecular genetics OMIM In 2 sibs and 2 unrelated women with autosomal dominant progressive external ophthalmoplegia with DNA deletions-6, Ronchi et al. (2013) identified 3 different heterozygous mutations in the DNA2 gene (601810.0001-601810.0003). The first mutation was identified by exome sequencing ...