A multiplex assay for the detection and mapping of complex glycerol kinase deficiency.
BACKGROUND
Glycerol kinase deficiency (GKD) is an X-linked recessive disorder that presents in both isolated and complex forms. The contiguous deletion that leads to GKD also commonly affects NR0B1 (DAX1), the gene associated with adrenal hypoplasia congenita, and DMD, the Duchenne muscular dystrophy gene. Molecular testing to delineate this deletion is expensive and has only limited availability.


METHODS
We designed a multiplex PCR assay for the detection and mapping of a contiguous deletion potentially affecting the IL1RAPL1, NR0B1, GK, and DMD genes in a 29-month-old male patient with GKD.


RESULTS
Multiplex PCR detected a contiguous deletion that involved the IL1RAPL1, NR0B1, GK, and DMD genes. Although the patient had a creatine kinase concentration within the reference interval, further mapping with PCR revealed that exon 74 was the last intact exon at the 3' end of the DMD gene.


CONCLUSIONS
Multiplex PCR is an effective and inexpensive way to detect and map the contiguous deletion in cases of complex GKD. The extension of a deletion to include DMD exon 75 in a patient with a creatine kinase concentration within the reference interval suggests that this region of the gene may not be essential for protein function.
Klein
Roger D
RD
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55901, USA. roger.klein@yale.edu
Thorland
Erik C
EC
Gonzales
Patrick R
PR
Beck
Patricia A
PA
Dykas
Daniel J
DJ
McGrath
James M
JM
Bale
Allen E
AE
D002675:Child, Preschool; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics; D016189:Dystrophin / Q000235:genetics; D005091:Exons; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis; D005991:Glycerol Kinase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D053577:Interleukin-1 Receptor Accessory Protein; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D017472:Receptors, Interleukin-1 / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012016:Reference Values; D012097:Repressor Proteins / Q000235:genetics
D057137:DAX-1 Orphan Nuclear Receptor; C484258:DMD protein, human; D004268:DNA-Binding Proteins; D016189:Dystrophin; C407643:IL1RAPL1 protein, human; D053577:Interleukin-1 Receptor Accessory Protein; C539965:NR0B1 protein, human; D017472:Receptors, Interleukin-1; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D005991:Glycerol Kinase