Two male sibs with severe micrognathia and a missense variant in MED12.

TitleTwo male sibs with severe micrognathia and a missense variant in MED12.
Publication TypeJournal Article
Year of Publication2016
AuthorsPrescott, TE, Kulseth, MAnn, Heimdal, KR, Stadheim, B, Hopp, E, Gambin, T, Akdemir, ZHCoban, Jhangiani, SN, Muzny, DM, Gibbs, RA, Lupski, JR, Stray-Pedersen, A
JournalEur J Med Genet
Date Published2016 Aug
KeywordsExons, Genes, X-Linked, Genetic Association Studies, Genotype, Humans, Infant, Male, Mediator Complex, Micrognathism, Mutation, Missense, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Severity of Illness Index, Siblings, Tomography, X-Ray Computed, X Chromosome Inactivation

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 JournalEur J Med Genet
PubMed ID27286923

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