SETD2 related overgrowth syndrome: Presentation of four new patients and review of the literature
| Autor: | Bertrand Isidor, Kimberly A. Aldinger, Valérie Cormier-Daire, Sophie Rondeau, William B. Dobyns, Boris Keren, Pauline Marzin, Jean Luc Alessandri, Delphine Héron |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Joint hypermobility Pediatrics medicine.medical_specialty Intellectual disability Genetics Humans Medicine Missense mutation Child Growth Disorders Genetics (clinical) Sotos Syndrome business.industry Macrocephaly Infant Histone-Lysine N-Methyltransferase medicine.disease Autism spectrum disorder Child Preschool Overgrowth syndrome Mutation Speech delay Autism Female medicine.symptom business |
| Zdroj: | American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 181:509-518 |
| ISSN: | 1552-4876 1552-4868 |
| DOI: | 10.1002/ajmg.c.31746 |
| Popis: | The common genes responsible for overgrowth syndromes play key roles in regulating transcription through histone modification and chromatin modeling. The SETD2 gene encoding a H3K36 trimethyltransferase is implicated in Sotos-like syndrome. This syndrome is characterized by postnatal overgrowth, macrocephaly, obesity, speech delay, and advanced carpal ossification. We report four new patients with constitutional SETD2 mutations and review nine earlier reported patients. Almost all patients presented with macrocephaly associated with advanced stature and obesity in half of the cases. In addition to these principal manifestations, neurodevelopmental disorders are common such as intellectual disability (83%), autism spectrum disorders (89%), and behavioral difficulties (100%) with aggressive outbursts (83%). A variety of features such as joint hypermobility (29%), hirsutism (33%), and naevi (50%) were also reported. Constitutional SETD2 mutations are intragenic loss-of-function variants with truncating (69%) and missense (31%) mutations. Functional studies are necessary to improve understanding of the pathogenicity of some missense SETD2 mutations. |
| Databáze: | OpenAIRE |
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