TY - JOUR
T1 - Evidence for Increased SOX3 Dosage as a Risk Factor for X-Linked Hypopituitarism and Neural Tube Defects
AU - Bauters, Marijke
AU - Frints, Suzanna G.
AU - Van Esch, Hilde
AU - Spruijt, Liesbeth
AU - Baldewijns, Marcella M.
AU - de Die-Smulders, Christine E. M.
AU - Fryns, Jean-Pierre
AU - Marynen, Peter
AU - Froyen, Guy
PY - 2014/8
Y1 - 2014/8
N2 - Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X; 22)(q27; q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects.
AB - Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X; 22)(q27; q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects.
KW - X-linked hypopituitarism
KW - growth hormone deficiency
KW - SOX3 duplication
KW - neural tube defect
KW - gene overexpression
U2 - 10.1002/ajmg.a.36580
DO - 10.1002/ajmg.a.36580
M3 - Article
SN - 1552-4825
VL - 164
SP - 1947
EP - 1952
JO - American Journal of Medical Genetics Part A
JF - American Journal of Medical Genetics Part A
IS - 8
ER -