RGD Reference Report - Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency. - Rat Genome Database

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Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency.

Authors: Lissens, W  De Meirleir, L  Seneca, S  Liebaers, I  Brown, GK  Brown, RM  Ito, M  Naito, E  Kuroda, Y  Kerr, DS  Wexler, ID  Patel, MS  Robinson, BH  Seyda, A 
Citation: Lissens W, etal., Hum Mutat 2000;15(3):209-19.
RGD ID: 731230
Pubmed: PMID:10679936   (View Abstract at PubMed)
DOI: DOI:10.1002/(SICI)1098-1004(200003)15:3<209::AID-HUMU1>3.0.CO;2-K   (Journal Full-text)

Defects in the pyruvate dehydrogenase (PDH) complex are an important cause of primary lactic acidosis, a frequent manifestation of metabolic disease in children. Clinical symptoms can vary considerably in patients with PDH complex deficiencies, and almost equal numbers of affected males and females have been identified, suggesting an autosomal recessive mode of inheritance of the disease. However, the great majority of PDH complex deficiencies result from mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1). The major factors that contribute to the clinical variation in E1alpha deficiency and its resemblance to a recessive disease are developmental lethality in some males with severe mutations and the pattern of X-inactivation in females. To date, 37 different missense/nonsense and 39 different insertion/deletion mutations have been identified in the E1alpha subunit gene of 130 patients (61 females and 69 males) from 123 unrelated families. Insertion/deletion mutations occur preferentially in exons 10 and 11, while missense/nonsense mutations are found in all exons. In males, the majority of missense/nonsense mutations are found in exons 3, 7, 8 and 11, and three recurrent mutations at codons R72, R263 and R378 account for half of these patients with missense/nonsense mutations (25 of 50). A significantly lower number of females is found with missense/nonsense mutations (25). However, 36 females out of 55 affected patients have insertion/deletion mutations. The total number of female and male patients is thus almost the same, although a difference in the distribution of the type of mutations is evident between both sexes. In many families, the parents of the affected patients were studied for the presence of the PDHA1 mutation. The mutation was never present in the somatic cells of the father; in 63 mothers studied, 16 were carriers (25%). In four families, the origin of the new mutation was determined to be twice paternal and twice maternal.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDHA1Humanpyruvate decarboxylase deficiency  IAGP DNA:mutations:multiple (human)RGD 
Pdha1Ratpyruvate decarboxylase deficiency  ISOPDHA1 (Homo sapiens)DNA:mutations:multiple (human)RGD 
Pdha1Mousepyruvate decarboxylase deficiency  ISOPDHA1 (Homo sapiens)DNA:mutations:multiple (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdha1  (pyruvate dehydrogenase E1 subunit alpha 1)

Genes (Mus musculus)
Pdha1  (pyruvate dehydrogenase E1 alpha 1)

Genes (Homo sapiens)
PDHA1  (pyruvate dehydrogenase E1 subunit alpha 1)


Additional Information