Copy number variants of Ras/MAPK pathway genes in patients with isolated cryptorchidism

Summary Cryptorchidism is the most common congenital disorder in boys, but the cause for most cases remains unknown. Patients with Noonan Syndrome are characterized by a typical face, growth retardation, congenital heart defects, learning disabilities and cryptorchidism. Copy number variations of Ras/MAPK pathway genes are unusual in patients with several clinical features of Noonan Syndrome; however, they have not been studied in patients with only one feature of this condition, such as cryptorchidism. Our aim was to determine whether patients with isolated cryptorchidism exhibit Ras/MAPK pathway gene copy number variations (CNVs). Fifty-nine patients with isolated cryptorchidism and negative for mutations in genes associated with Noonan Syndrome were recruited. Determination of Ras/MAPK pathway gene CNVs was performed by Comparative Genome Hybridization array. A CNV was identified in two individuals, a ~175 kb microduplication at 3p25.2, partially including RAF1. A similar RAF1 microduplication has been observed in a patient with testicular aplasia. This suggests that some patients with isolated cryptorchidism may harbor Ras/MAPK pathway gene CNVs.