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Interstitial 10p11.23–p12.1 microdeletions associated with developmental delay, craniofacial abnormalities, and cryptorchidism
Author(s) -
Mroczkowski Henry J.,
Arnold Georgianne,
Schneck Francis X.,
Rajkovic Aleksandar,
Yatsenko Svetlana A.
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36627
Subject(s) - haploinsufficiency , biology , craniofacial , genetics , locus (genetics) , phenotype , disorders of sex development , craniofacial abnormality , gene , chromosomal region , abnormality , medicine , psychiatry
Cryptorchidism is the most common genital problem encountered in males and is associated with many chromosomal disorders; however, the genetic factors are mostly unknown. To delineate critical genes affecting testicular migration, we performed genotype–phenotype correlation in patients with deletions involving the proximal short arm of chromosome 10 (10p11–p12), a rare abnormality characterized by developmental delay, craniofacial abnormalities, and in some cases, cryptorchidism. Here we report on a male patient with developmental delay, mild craniofacial dysmorphism, bilateral cryptorchidism, and an 850‐kb deletion, within the 10p11.2 region, involving three genes— MKX , ARMC4 , and MPP7 —as determined by array comparative genomic hybridization analysis. Comparison with four previously reported male patients with overlapping deletions revealed a 140‐kb common region, containing the MKX gene, in association with cryptorchidism. The MKX gene is a member of the three amino acid loop extension (TALE) superclass of homeobox genes that is expressed in developing male gonads (male gonadal ridge and testis cords) in temporal relationship to SOX9 , a critical regulator of sexual differentiation. Our results suggest that haploinsufficiency of the MKX gene may affect the developmental process during testis migration or serve as a genetic susceptibility locus for cryptorchidism. We propose that deletions of the proximal 10p represent a contiguous gene syndrome; therefore, patients may present with a complex phenotype, depending on the extent of the deletion. © 2014 Wiley Periodicals, Inc.