With NGS laying the ground-work for gene discovery, the next step was the analysis of gene pathways using qPCR studies; therefore, the most-studied genes in vertebrates that are involved in male pathway were sox9, amh, nr5a1, nrob1
, and wt1 [34-36].
Xp21 contiguous gene deletion is a microdeletion syndrome with intellectual disability,congenital adrenal hypoplasia,glyserol kinase deficiency and dystrophinopathy.It is a rare disease, reported in around 100 boys and 8 girls in the literature to date.In Xp21 locus,there are dystrophin, GK,DAX1 (NROB1
) and IL1RAPL1 genes which are related with dystrophinopathy,glycerol kinase, congenital adrenal hypoplasia and intellectual disability, respectively.In our patient,there was Xp21 deletion including dystrophin,GK,DAX1 and IL1RAPL1 genes.
WT1 gene, as a transcription factor, directly or indirectly interacts with a number of genes involved in cell cycle and neoplasia, including HIF1A, AREG, SRY, NROB1
, SOX9, IGF2, MDM4, BRCA1, TP53, and SP1 (NCBI Gene).
The findings in our patients were supportive of AHC, as seen in patients with mutations or deletions of the DAX-1 (NROB1
) gene at the X chromosome (6,7), defects of steroidogenic factor 1 gene at the 9q33 chromosome (8), and IMAGe syndrome (9).
De Vroede et al., "Clinical case seminar: an amino-terminal DAX1 (NROB1
) missense mutation associated with isolated mineralocorticoid deficiency," Journal of Clinical Endocrinology and Metabolism, vol.
Cryptorchidism is associated with AHC (11-15) and therefore may also be observed in complex GK deficiency in patients in whom the deletion involves NROB1
. Patients with deletions extending into the DMD gene generally have signs and symptoms of classic DMD.
The variations in the expression of 17 genes (underlined in Table 2) are involved in specific neuronal pathways, such as neuronal cell structure (GPM6B, PRPH, RELN), neural signaling and development (HOXB2, ELAVLI, EFNB1, NRG2, NELL1, MDK, GFRA1), synaptogenesis and steroid biosynthesis (SYCP2, PCDH17, STX1B2, SCG5, Nstage 4 diseasel, GATA3, NROB1