RGD Reference Report - Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency. - Rat Genome Database

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Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency.

Authors: Kugler, W  Breme, K  Laspe, P  Muirhead, H  Davies, C  Winkler, H  Schroter, W  Lakomek, M 
Citation: Kugler W, etal., Hum Genet. 1998 Oct;103(4):450-4.
RGD ID: 1600632
Pubmed: PMID:9856489   (View Abstract at PubMed)

Glucose-6-phosphate isomerase (GPI) deficiency, an autosomal recessive genetic disorder with the typical manifestation of nonspherocytic haemolytic anaemia, can be associated in some cases with neurological impairment. GPI has been found to be identical to neuroleukin (NLK), which has neurotrophic and lymphokine properties. To focus on the possible effects of GPI mutations on the central nervous system through an effect on neuroleukin activity, we analysed DNA isolated from two patients with severe GPI deficiency, one of them with additional neurological deficits, and their families. The neurologically affected patient (GPI Homburg) is compound heterozygous for a 59 A-->C (H20P) and a 1016 T-->C (L339P) exchange. Owing to the insertion of proline, the H20P and L339P mutations are likely to affect the folding and activity of the enzyme. In the second family studied, the two affected siblings showed no neurological symptoms. The identified mutations are 1166 A-->G (H389R) and 1549 C-->G (L517V), which are located at the subunit interface. We propose that mutations that lead to incorrect folding destroy both catalytic (GPI) and neurotrophic (NLK) activities, thereby leading to the observed clinical symptoms (GPI Homburg). Those alterations at the active site, however, that allow correct folding retain the neurotrophic properties of the molecule (GPI Calden).

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congenital hemolytic anemia  IAGP 1600632Severe GPI deficiency with neurologic deficits DNA:point_mutations:CDS:compound heterozygote for 59A>C (amino acid H20P), and 1016T>C (amino acid L339P)RGD 
congenital hemolytic anemia  ISOGPI (Homo sapiens)1600632; 1600632Severe GPI deficiency with neurologic deficitsRGD 
intellectual disability  IAGP 1600632Severe GPI deficiency with neurologic deficits DNA:point_mutations:CDS:compound heterozygote for 59A>C (amino acid H20P), and 1016T>C (amino acid L339P)RGD 
intellectual disability  ISOGPI (Homo sapiens)1600632; 1600632Severe GPI deficiency with neurologic deficitsRGD 
neuromuscular disease  IAGP 1600632Severe GPI deficiency with neurologic deficits DNA:point_mutations:CDS:compound heterozygote for 59A>C (amino acid H20P), and 1016T>C (amino acid L339P)RGD 
neuromuscular disease  ISOGPI (Homo sapiens)1600632; 1600632Severe GPI deficiency with neurologic deficitsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gpi  (glucose-6-phosphate isomerase)

Genes (Mus musculus)
Gpi1  (glucose-6-phosphate isomerase 1)

Genes (Homo sapiens)
GPI  (glucose-6-phosphate isomerase)


Additional Information