A novel mutation in SOX3 polyalanine tract: a case of kabuki syndrome with combined pituitary hormone deficiency harboring double mutations in MLL2 and SOX3.

[kabuki syndrome]

Both duplications encompassing SOX 3 and loss -of function mutations in SOX 3 have been reported in a minor portion of X-linked isolated growth hormone deficiency (GHD ) or combined pituitary hormone deficiency (CPHD ) patients with or without mental retardation .We report a Japanese male patient with molecularly confirmed Kabuki syndrome who was found to have CPHD . We analyzed all coding exons and flanking introns of currently known nine genes responsible for CPHD by PCR-based sequencing .In this CPHD patient , we identified a novel hemizygous 21 -base pair deletion , resulting in the loss of 7 alanine residues from polyalanine (PA ) tracts of SOX 3 . The clinically and endocrinologically normal mother of the patient carried the same deletion in a heterozygous manner . In vitro experiments showed that the del 7 A SOX 3 had increased transactivation of the HESX 1 promoter .O ur study provides additional evidence that deletion in PA tracts of SOX 3 is associated with hypopituitarism . Female carriers of SOX 3 PA tract deletions will show a broad phenotypic spectrum , ranging from clinically normal to CPHD .