Received on April 27, 2006
Accepted on July 6, 2006

Molecular Diagnostics and Genetics

A Multiplex Assay for the Detection and Mapping of Complex Glycerol Kinase Deficiency

¹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
² Department of Genetics, Yale University School of Medicine, New Haven, CT

^* To whom correspondence should be addressed. E-mail: roger.klein{at}yale.edu.

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 with GKD.

Results: Multiplex PCR detected a contiguous deletion that involves 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.