Xq26.1-26.3 duplication including MOSPD1 and GPC3 identified in boy with short stature and double outlet right ventricle.

Xq25q26 duplication syndrome has been reported in individuals with clinical features such as short stature, intellectual disability, syndromic facial appearance, small hands and feet, and genital abnormalities. The symptoms are related to critical chromosome regions including Xq26.1-26.3. In this particular syndrome, no patient with congenital heart disease was previously reported. Here, we report a 6-year-old boy with typical symptoms of Xq25q26 duplication syndrome and double outlet right ventricle (DORV) with pulmonary atresia (PA). He had the common duplicated region of Xq25q26 duplication syndrome extending to the distal region including the MOSPD1 locus. MOSPD1 regulates transforming growth factor beta (TGFß) 2,3 and may be responsible for cardiac development including DORV. In the patient's lymphocytes, mRNA expression of TGFß2 was lower than control, and might cause DORV as it does in TGFß2-deficient mice. Therefore, MOSPD1 is a possible candidate gene for DORV, probably in combination with GPC3. Further studies of the combined functions of MOSPD1 and GPC3 are needed, and identification of additional patients with MOSPD1 and GPC3 duplication should be pursued.