Clinical heterogeneity and molecular findings in five Polish patients with glycerol kinase deficiency: investigation of two splice site mutations with computerized splice junction analysis and Xp21 gene-specific mRNA analysis.

• Five cases of glycerol kinase deficiency are presented with clinical, biochemical, and genetic results. Two had the glycerol kinase deficiency as part of an Xp21 contiguous gene deletion syndrome-complex form-and three had an isolated form of the enzyme deficiency. In these we found two splice site mutations (IVS1+4A>G, IVS9-1G>T) and one insertion (1393_1394insG). In patients with the complex form, a deletion of the DAX1, GK genes and the distal part of the DMD gene was found. A computerized study was performed to predict the effects of the splice site mutations. It showed that the IVS9-1G>T mutation substantially altered and removed the wild-type site and enhanced a cryptic site seven nucleotides downstream, and that the IVS1+4A>G diminished the strength of the wild-type donor site from strong to leaky. To verify these predictions, we developed an RT-PCR system with gene-specific primers that exclusively amplifies the Xp21 glycerol kinase gene transcript. Identification of individuals at risk is motivated by a need to avoid delay in a correct diagnosis. For reliable identification of heterozygotes for isolated glycerol kinase deficiency, knowledge of the specific mutation in the proband is required. This is easily obtained with the RT-PCR analyses developed in this study.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Annan klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Other Clinical Medicine (hsv//eng)

Nyckelord

Adrenal Insufficiency

genetics

Chromosomes

Human

X

DAX-1 Orphan Nuclear Receptor

DNA Mutational Analysis

DNA Primers

chemistry

DNA-Binding Proteins

chemistry

deficiency

genetics

Gene Deletion

Glycerol

blood

urine

Glycerol Kinase

chemistry

deficiency

genetics

Humans

Infant

Newborn

Male

Molecular Sequence Data

Muscular Dystrophy

Duchenne

genetics

Mutation

Poland

Polymorphism

Single-Stranded Conformational

RNA

Messenger

genetics

metabolism

Receptors

Retinoic Acid

chemistry

deficiency

genetics

Repressor Proteins

chemistry

genetics

Reverse Transcriptase Polymerase Chain Reaction

methods

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)