Genetic Overlap between Holoprosencephaly and Kallmann Syndrome.

[kallmann syndrome]

Patients with Kallmann syndrome (KS ; congenital hypogonadotropic hypogonadism and decreased /absent sense of smell ), septo-optic dysplasia (SOD ), or holoprosencephaly (HPE ) reportedly have midline defects . In this study , we investigate a genetic overlap between KS , SOD , and HPE . Nineteen subjects (18 males , 1 female ) with KS and without mutations in the known KS genes were screened for mutations in SOX 2 , SHH , SIX 3 ,TGIF 1 ,TDGF 1 ,FOXH 1 ,GLI 2 , and GLI 3 . One male carried 2 heterozygous missense changes , one in SIX 3 (c .428 G >A , p .G 143 D ) and the other in GLI 2 (c .2509 G >A , p .E 837 K ). Both of these genes have been implicated in the etiology of HPE and neither of these changes were present in 200 control subjects . Other variants found among the subjects were known polymorphisms . KS and HPE may display a genetic overlap . The involvement of genes implicated in the etiology of midline defects in patients with KS warrants further studies .