Combined oxidative phosphorylation defect type 13

General Information (adopted from Orphanet):

Synonyms, Signs: COXPD13
Number of Symptoms 40
OrphanetNr: 319514
OMIM Id: 614932
ICD-10: G71.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial disorder due to a defect in mitochondrial protein synthesis
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

PNPT1 (COXPD13 / DFNB70 / OLD35) encodes the mitochondrial polynucleotide phosphorylase (PNPase). PNPase is predominantly localized in the mitochondrial intermembrane space and is implicated in RNA targeting to human mitochondria. Mutations in PNPT1 impair this RNA import into mitochondria and cause respiratory chain deficiencies depending on the mutation. A homozygous PNPT1 missense mutation (c.1160A>G) is described in PMID:23084291. This substitution disrupts the trimerization of the protein. No inheritance is described (PMID:23084291). Another homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of the highly conserved PNPase residue within the second RNase-PH domain in a family affectes autosomal-recessive nonsyndromic hearing impairment (PMID:23084290). No mitochondrial disorders are described (PMID:23084290).

Symptom Information: Sort by abundance 

1
 (HPO:0008872) Feeding difficulties in infancy 23084291 IBIS 153 / 7739
2
 (HPO:0011471) Gastrostomy tube feeding in infancy 23084291 IBIS 3 / 7739
3
 (HPO:0002013) Vomiting 23084291 IBIS 191 / 7739
4
 (HPO:0002151) Increased serum lactate 23084291 IBIS 92 / 7739
5
 (HPO:0012103) Abnormality of the mitochondrion 23084291 IBIS 7 / 7739
6
 (HPO:0011922) Abnormal activity of mitochondrial respiratory chain 23084291 IBIS 1 / 7739
7
 (HPO:0011924) Decreased activity of mitochondrial complex III 23084291 IBIS 22 / 7739
8
 (HPO:0008347) Decreased activity of mitochondrial complex IV 23084291 IBIS 31 / 7739
9
 (HPO:0200125) Mitochondrial respiratory chain defects 23084291 IBIS 6 / 7739
10
 (HPO:0003554) Type 2 muscle fiber atrophy 23084291 IBIS 14 / 7739
11
 (HPO:0003803) Type 1 muscle fiber predominance 23084291 IBIS 12 / 7739
12
 (HPO:0003202) Skeletal muscle atrophy 23084291 IBIS 281 / 7739
13
 (HPO:0001252) Muscular hypotonia 23084291 IBIS 990 / 7739
14
 (HPO:0001290) Generalized hypotonia 23084291 IBIS 51 / 7739
15
 (HPO:0008936) Muscular hypotonia of the trunk 23084291 IBIS 77 / 7739
16
 (HPO:0001266) Choreoathetosis 23084291 IBIS 57 / 7739
17
 (HPO:0001324) Muscle weakness 23084291 IBIS 859 / 7739
18
 (HPO:0002421) Poor head control 23084291 IBIS 23 / 7739
19
 (HPO:0002490) Increased CSF lactate 23084291 IBIS 28 / 7739
20
 (HPO:0001298) Encephalopathy 23084291 IBIS 72 / 7739
21
 (HPO:0000762) Decreased nerve conduction velocity 23084291 IBIS 36 / 7739
22
 (HPO:0001332) Dystonia 23084291 IBIS 197 / 7739
23
 (HPO:0001263) Global developmental delay 23084291 IBIS 853 / 7739
24
 (HPO:0001344) Absent speech 23084291 IBIS 57 / 7739
25
 (HPO:0100660) Dyskinesia 23084291 IBIS 19 / 7739
26
 (HPO:0002015) Dysphagia 23084291 IBIS 301 / 7739
27
 (HPO:0001265) Hyporeflexia 23084291 IBIS 208 / 7739
28
 (HPO:0001510) Growth delay 23084291 IBIS 295 / 7739
29
 (MedDRA:10058799) Mitochondrial encephalomyopathy 23084291 IBIS 5 / 7739
30
 (OMIM) Encephalomyopathy 23084291 IBIS 2 / 7739
31
 (OMIM) Inability to hold head up 23084291 IBIS 2 / 7739
32
 (OMIM) Inability to sit or stand independently 23084291 IBIS 1 / 7739
33
 (OMIM) Increased serum and CSF lactate 23084291 IBIS 7 / 7739
34
 (OMIM) Lack of speech 23084291 IBIS 17 / 7739
35
 (OMIM) Liver shows mitochondrial respiratory chain deficiencies of complexes III and IV 23084291 IBIS 1 / 7739
36
 (OMIM) Loss of purposeful hand movements 23084291 IBIS 2 / 7739
37
 (OMIM) Motor regression 23084291 IBIS 3 / 7739
38
 (OMIM) Muscle biopsy shows peripheral accumulation of abnormal mitochondria 23084291 IBIS 1 / 7739
39
 (OMIM) No head control 23084291 IBIS 2 / 7739
40
 (OMIM) T2-weighted hyperintensities in the putamen and caudate nuclei 23084291 IBIS 1 / 7739

Associated genes:

PNPT1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Vedrenne et al. (2012) reported 2 sibs, born of consanguineous Moroccan parents, with early onset severe encephalomyopathy, choreoathetotic movements, and combined mitochondrial respiratory chain deficiency. The first child was a girl who had normal development for the first ...
Molecular genetics OMIM By exome sequencing of 2 Moroccan sibs with early-onset encephalomyopathy, Vedrenne et al. (2012) identified a homozygous mutation in the PNPT1 gene (Q387R; 610316.0001). Biochemical studies showed that the mutation impaired normal import of several RNA species into ...