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

Autor: Prescott TE; Department of Medical Genetics, Oslo University Hospital, 0424, Oslo, Norway. Electronic address: prescott@online.no., Kulseth MA; Department of Medical Genetics, Oslo University Hospital, 0424, Oslo, Norway., Heimdal KR; Department of Medical Genetics, Oslo University Hospital, 0424, Oslo, Norway., Stadheim B; Department of Medical Genetics, Oslo University Hospital, 0424, Oslo, Norway., Hopp E; Department of Radiology and Nuclear Medicine, Oslo University Hospital, 0424, Oslo, Norway., Gambin T; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA; Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland., Coban Akdemir ZH; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA., Jhangiani SN; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA; Human Genome Sequencing Center (HGSC), Baylor College of Medicine, Houston, TX, 77030, USA., Muzny DM; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA; Human Genome Sequencing Center (HGSC), Baylor College of Medicine, Houston, TX, 77030, USA., Gibbs RA; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA; Human Genome Sequencing Center (HGSC), Baylor College of Medicine, Houston, TX, 77030, USA., Lupski JR; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA; Human Genome Sequencing Center (HGSC), Baylor College of Medicine, Houston, TX, 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA; Texas Children's Hospital, Houston, TX, 77030, USA., Stray-Pedersen A; Baylor-Hopkins Center for Mendelian Genomics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA; Norwegian National Unit for Newborn Screening, Oslo University Hospital, 0424, Oslo, Norway.
Jazyk: angličtina
Zdroj: European journal of medical genetics [Eur J Med Genet] 2016 Aug; Vol. 59 (8), pp. 367-72. Date of Electronic Publication: 2016 Jun 07.
DOI: 10.1016/j.ejmg.2016.06.001
Abstrakt: 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.
(Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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