COG6-CDG: Novel variants and novel malformation
| Autor: | Lara Cirnigliaro, Paolo Bianchi, Luisa Sturiale, Domenico Garozzo, Giovanna Mangili, Liesbeth Keldermans, Renata Rizzo, Gert Matthijs, Agata Fiumara, Jaak Jaeken, Rita Barone |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Embryology
Glycosylation combined N- and O-glycosylation defect Health Toxicology and Mutagenesis Golgi Apparatus congenital ano-rectal malformations CONGENITAL DISORDERS Toxicology PATIENT O-GLYCOSYLATION Congenital Disorders of Glycosylation Humans SUBUNIT-6 TRAFFICKING congenital disorder of glycosylation (CDG) MUTATION Science & Technology Vaginal Fistula Infant Newborn N-GLYCOSYLATION GENE DEFICIENCY Adaptor Proteins Vesicular Transport COG6 Pediatrics Perinatology and Child Health Female OLIGOMERIC GOLGI-COMPLEX corpus callosum dysgenesis Life Sciences & Biomedicine Developmental Biology |
| Popis: | BACKGROUND: Deficiency of Conserved Oligomeric Golgi (COG) subunits (COG1-8) is characterized by both N- and O-protein glycosylation defects associated with destabilization and mislocalization of Golgi glycosylation machinery components (COG-CDG). Patients with COG defects present with neurological and multisystem involvement and possible malformation occurrence. Eighteen patients with COG6-CDG (COG6 mutations) were reported to date. We describe a patient with COG6-CDG with novel variants and a novel clinical feature namely a congenital recto-vaginal fistula. METHODS: In-depth serum N- and O-glycosylation structural analyses were conducted by MALDI-TOF mass spectrometry. COG6 variants were identified by a gene panel and confirmed by Sanger sequencing. RESULTS: This female newborn presented with facial dysmorphism, distal arthrogryposis and recurrent stool discharges per vaginam. A double-contrast barium-enema X-ray study revealed a dehiscence (approximately 5 mm) at the anterior wall of the rectal ampoule communicating with the vagina consistent with a recto-vaginal fistula. She had developmental delay, corpus callosum dysgenesis, liver and gastrointestinal involvement, hyperthermia episodes and early demise. Serum N- and O-glycosylation analyses pointed to a profound Golgi disarrangement. We identified two novel variants in COG6: a deletion of 1 bp mutation c.823delA creating a shift in the reading frame and a premature stop codon and a 3 bp deletion (c.1141_1143delCTC) producing an in-frame deletion of 1 amino acid. CONCLUSION: The congenital recto-vaginal fistula is a rare type of anorectal malformation that, to our knowledge, has not been reported in patients with a COG6 defect nor in patients with other COG defects. This study broadens COG6-CDG genetic landscape and spectrum of malformations. ispartof: BIRTH DEFECTS RESEARCH vol:114 issue:5-6 pages:165-174 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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