Two male sibs with severe micrognathia and a missense variant in MED12
Trine E. Prescott , Mari Ann Kulseth , Ketil R. Heimdal , Barbro Stadheim , Einar Hopp , Tomasz Gambin , Zeynep H. Coban Akdemir , Shalini N. Jhangiani , Donna M. Muzny , Richard A. Gibbs , James R. Lupski , Asbjørg Stray-Pedersen
AbstractMissense 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.
|Journal series||European Journal of Medical Genetics, ISSN 1769-7212|
|Publication size in sheets||0.5|
|Score|| = 15.0, 27-03-2017, ArticleFromJournal|
= 20.0, 27-03-2017, ArticleFromJournal
|Publication indicators||: 2016 = 2.137 (2) - 2016=1.625 (5)|
|Citation count*||5 (2018-06-14)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.