COG6-CDG: Expanding the phenotype with emphasis on glycosylation defects involved in the causation of male disorders of sex development

Hanna Mandel, Nehama Cohen Kfir, Ayalla Fedida, Efrat Shuster Biton, Marwan Odeh, Limor Kalfon, Shani Ben-Harouch, Vered Fleischer Sheffer, Yoav Hoffman, Yael Goldberg, April Dinwiddie, Elena Dumin, Ayelet Eran, Liat Apel-Sarid, Dov Tiosano, Tzipora C. Falik-Zaccai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)402-407
Number of pages6
JournalClinical Genetics
Volume98
Issue number4
DOIs
StatePublished - 1 Oct 2020
Externally publishedYes

Funding

FundersFunder number
Teva Pharmaceutical Industries
Toa Pharmaceutical

    Keywords

    • COG6
    • congenital disorder of glycosylation (CDG)
    • disorder of sex development (DSD)

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