X-linked liver phosphorylase kinase deficiency is associated with mutations in the human liver phosphorylase kinase {alpha} subunit
- Wilhelmina Children`s Hospital, Utrecht (Netherlands)
- Clinical Genetic Centre, Utrecht (Netherlands)
- Univ. of Amsterdam (Netherlands)
Two Dutch patients with liver phosphorylase kinase (PhK) deficiency were studied for abnormalities in the PhK liver {alpha} ({alpha}{sub L}) subunit mRNA by reversed-transcribed-PCR (RT-PCR) and RNase protection assays. One patient, belonging to a large Dutch family that expresses X-linked liver PhK deficiency, had a C3614T mutation in the PhK {alpha}{sub L} coding sequence. The C3614T mutation leads to replacement of proline 1205 with leucine, which changes the composition of an amino acid region, containing amino acids 1195-1214 of the PhK {alpha}{sub L} subunit, that is highly conserved in different species. The patient showed normal levels of PhK {alpha}{sub L} mRNA. The second patient, from an unrelated family, was found to have a TCT (bp 419-421) deletion in the PhK {alpha}{sub L} coding sequence, resulting in a phenylalanine 141 deletion. The same deletion was found in the PhK {alpha}{sub L} coding sequence from lymphocytes of the patient`s mother, together with a normal PhK {alpha}{sub L} coding sequence. The phenylalanine that is absent in the PhK{alpha}{sub L} coding sequence of the second patient is a highly conserved amino acid between species. Both the C3614T mutation and the TCT (bp 419-421) deletion were not found in a panel of 80 control X chromosomes. On the basis of these results, it is postulated that the mutations found are responsible for liver PhK deficiency in the two patients investigated. 33 refs., 5 figs.
- OSTI ID:
- 70398
- Journal Information:
- American Journal of Human Genetics, Vol. 56, Issue 2; Other Information: PBD: Feb 1995
- Country of Publication:
- United States
- Language:
- English
Similar Records
Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: Molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase
Mutations in PHKA2 are responsible for X-linked liver glycogen storage disease