ClinVar

In a male with growth hormone deficiency and supernumerary digits, who had anterior pituitary hypoplasia, ectopic posterior pituitary, and infundibular hypoplasia by MRI (see 182230), McNay et al. (2007) identified a glu149-to-lys (E149K) mutation in the HESX1 gene. At age 12 years, the patient had hypoplasia of the scrotum and a small phallus, and his basal FSH of 2 IU/l did not respond to GnRH provocation whereas his LH increased from 4 IU/l to 8 IU/l; testosterone replacement was initiated. Experimental studies showed that, unlike wildtype HEXS1, the E149K mutant was unable to repress PROP1 (601538)-mediated activation, indicating that E149K is a functionally significant deleterious mutation. The mutation was not found in 100 control chromosomes. The patient's son, mother, and an older brother appeared to be unaffected carriers of the mutation. The authors speculated that the mutation was dominant with reduced penetrance or that the patient was compound heterozygous for E149K and an unidentified mutation within HESX1.