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 .

Diseases
Validation

Diseases presenting "mental retardation" symptom

achondroplasia

alexander disease

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

classical phenylketonuria

coats disease

cohen syndrome

cowden syndrome

cystinuria

dentin dysplasia

familial hypocalciuric hypercalcemia

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

lamellar ichthyosis

lymphangioleiomyomatosis

monosomy 21

phenylketonuria

primary hyperoxaluria type 1

proteus syndrome

pyruvate dehydrogenase deficiency

sneddon syndrome

triple a syndrome

wolf-hirschhorn syndrome

zellweger syndrome

This symptom has already been validated