FG syndrome, Lujan syndrome, and Ohdo syndrome, the Maat-Kievit-Brunner type, 
have been described as distinct syndromes with overlapping non-specific features 
and different missense mutations of the MED12 gene have been reported in all of 
them. We report a family including 10 males and 1 female affected with profound 
non-specific intellectual disability (ID) which was linked to a 30-cM region 
extending from Xp11.21 (ALAS2) to Xq22.3 (COL4A5). Parallel sequencing of all 
X-chromosome exons identified a frameshift mutation (c.5898dupC) of MED12. 
Mutated mRNA was not affected by non-sense mediated RNA decay and induced an 
additional abnormal isoform due to activation of cryptic splice-sites in exon 
41. Dysmorphic features common to most affected males were long narrow face, 
high forehead, flat malar area, high nasal bridge, and short philtrum. Language 
was absent or very limited. Most patients had a friendly personality. Cognitive 
impairment, varying from borderline to profound ID was similarly observed in 
seven heterozygous females. There was no correlation between cognitive function 
and X-chromosome inactivation profiles in blood cells. The severe degree of ID 
in male patients, as well as variable cognitive impairment in heterozygous 
females suggests that the duplication observed in the present family may have a 
more severe effect on MED12 function than missense mutations. In a cognitively 
impaired male from this family, who also presented with tall stature and 
dysmorphism and did not have the MED12 mutation, a 600-kb duplication at 17p13.3 
including the YWHAE gene, was found in a mosaic state.