Determination of bounds for the deletion at Xp21 in families with X-linked adreanal hypoplasia congenita
X-linked adrenal hypoplasia congenita [X-linked AHC, MIM#300200] is caused by mutation or deletion of the DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene-1) gene. The GK (glycerol kinase) gene, responsible for hyperglycerolemia [glycerol kinase deficiency (GKD), MIM#307030], and the DMD (dystrophin) gene, for Duchenne muscular dystrophy [DMD, #310200]/ Becker muscular dystrophy [BMD, #300376], are mapped at centromeric region to the DAX1 gene in Xp21 (Xpter- DAX1- GK - DMD -Xcen). About 1/3 of all AHC patients have the deletion of DAX1, GK and DMD genes as part of an Xp21 contiguous gene syndrome. Many of the patients are the Xp21 contiguous gene syndrome involving DAX1, GK and DMD.
We encountered three families with X-linked AHC. The deleted regions of these families vary in size. One family had a deletion only DAX1 and GK regions, but two families had deletions including DAX1, GK and DMD regions. We performed fluorescence in situ hybridization (FISH) analyses using XCyte X mBAND probe (MetaSystems) and using the BAC clones spanning the genes of DAX1, GK and DMD. And, we also performed PCR analyses to confirm the precise deleted regions in these families. There are many reports of the families with Xp21 deletion, but there are few reports described the precise breakpoints of the deleted regions in such families. We present the precise deleted regions of these families by molecular level.