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


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.
Author Trine E. Prescott - [Oslo University Hospital]
Trine E. Prescott,,
, Mari Ann Kulseth - [Oslo University Hospital]
Mari Ann Kulseth,,
, Ketil R. Heimdal - [Oslo University Hospital]
Ketil R. Heimdal,,
, Barbro Stadheim - [Oslo University Hospital]
Barbro Stadheim,,
, Einar Hopp - [Oslo University Hospital]
Einar Hopp,,
, Tomasz Gambin (FEIT / IN)
Tomasz Gambin,,
- The Institute of Computer Science
, Zeynep H. Coban Akdemir - [Baylor College of Medicine]
Zeynep H. Coban Akdemir,,
, Shalini N. Jhangiani - Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas [Baylor College of Medicine]
Shalini N. Jhangiani,,
, Donna M. Muzny - [Baylor College of Medicine]
Donna M. Muzny,,
, Richard A. Gibbs - Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas [Baylor College of Medicine]
Richard A. Gibbs ,,
et al.`
Journal seriesEuropean Journal of Medical Genetics, ISSN 1769-7212
Issue year2016
Publication size in sheets0.5
ASJC Classification2716 Genetics(clinical); 1311 Genetics; 2700 General Medicine
Languageen angielski
MED12.pdf 970.2 KB
Score (nominal)20
Score sourcejournalList
ScoreMinisterial score = 15.0, 15-05-2020, ArticleFromJournal
Ministerial score (2013-2016) = 20.0, 15-05-2020, ArticleFromJournal
Publication indicators WoS Citations = 5; Scopus Citations = 3; GS Citations = 7.0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.909; WoS Impact Factor: 2016 = 2.137 (2) - 2016=1.625 (5)
Citation count*9 (2020-07-27)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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