COG6-CDG: Expanding the phenotype with emphasis on glycosylation defects involved in the causation of male disorders of sex development
| Autor: | Yoav Hoffman, Tzipora C. Falik-Zaccai, Ayelet Eran, Hanna Mandel, Efrat Shuster Biton, Limor Kalfon, April Dinwiddie, Liat Apel‐Sarid, Ayalla Fedida, Elena Dumin, Marwan Odeh, Vered Fleischer Sheffer, Dov Tiosano, Nehama Cohen Kfir, Yael Goldberg, Shani Ben‐Harouch |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male congenital hereditary and neonatal diseases and abnormalities Microcephaly Glycosylation Disorders of Sex Development 030105 genetics & heredity Biology Glycoprotein metabolism Mixed Function Oxygenases 03 medical and health sciences chemistry.chemical_compound Congenital Disorders of Glycosylation Exome Sequencing Genetics medicine Humans Disorders of sex development Genetics (clinical) Exome sequencing Sequence Deletion Directing attention Siblings Homozygote Infant Newborn medicine.disease Phenotype Adaptor Proteins Vesicular Transport 030104 developmental biology chemistry RNA splicing Mutation Female |
| Zdroj: | Clinical geneticsREFERENCES. 98(4) |
| ISSN: | 1399-0004 |
| Popis: | COG6-congenital disorder of glycosylation (COG6-CDG) is caused by biallelic mutations in COG6. To-date, 12 variants causing COG6-CDG in less than 20 patients have been reported. Using whole exome sequencing we identified two siblings with a novel homozygous deletion of 26 bp in COG6, creating a splicing variant (c.518_540 + 3del) and a shift in the reading frame. The phenotype of COG6-CDG includes growth and developmental retardation, microcephaly, liver and gastrointestinal disease, hypohydrosis and recurrent infections. We report two patients with novel phenotypic features including bowel malrotation and ambiguous genitalia, directing attention to the role of glycoprotein metabolism in the causation of disorders of sex development (DSD). Searching the glycomic literature, we identified 14 CDGs including males with DSD, a feature not previously accentuated. This study broadens the genetic and phenotypic spectrum of COG6-CDG and calls for increasing awareness to the central role of glycosylation processes in development of human sex and genitalia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text