|Title||Two male sibs with severe micrognathia and a missense variant in MED12.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Prescott, TE, Kulseth, MAnn, Heimdal, KR, Stadheim, B, Hopp, E, Gambin, T, Akdemir, ZHCoban, Jhangiani, SN, Muzny, DM, Gibbs, RA, Lupski, JR, Stray-Pedersen, A|
|Journal||Eur J Med Genet|
|Date Published||2016 Aug|
Missense variants in MED12 cause three partially overlapping dysmorphic X-linked intellectual disability (XLID) syndromes: Lujan-Fryns syndrome (also known as Lujan syndrome), FG syndrome (also known as Opitz-Kaveggia syndrome) and X-linked Ohdo syndrome. We report a family with two severely micrognathic male sibs, a 10½ year old boy and a fetus, in which hemizygosity for a previously unreported missense variant in exon 13 of MED12 (NM_005120.2), c.1862G > A, p.(Arg621Gln) was detected by whole exome sequencing. The affected sibs shared no other rare variant with relevance to the phenotype. X-chromosome inactivation in blood was completely skewed (100:0) in the unaffected heterozygous mother, most likely as a result of preferential inactivation of the X-chromosome harbouring the missense variant in MED12. Neither the unaffected brother nor the unaffected maternal grandfather carried the missense variant in MED12. In the 10½ year old boy, upper airway obstruction secondary to Pierre Robin sequence necessitated a tracheostomy for the first 10 months of life. He has mild to moderate intellectual disability and some dysmorphic features seen in MED12-related syndromes. In addition, he has a horizontal gaze paresis, anomalies of the inner ear, and a cervical block vertebra. This report contributes to the expanding phenotypic range associated with MED12-mutations.
|Alternate Journal||Eur J Med Genet|