COG6‐related prenatal phenotype (CDG2L): Clinico‐pathological report and review of the literature

• Published in: Molecular genetics & genomic medicine Vol. 13; no. 4; pp. e2442 - n/a
• Main Authors: Guterman, Sarah, Feresin, Agnese, Boutaud, Lucile, Jacquin, Clémence, Lyonnet, Stanislas, Bernard, Jean‐Pierre, Colmant, Claire, Roth, Philippe, Bourgon, Nicolas, Mace, Pierre, Thoreau, Alice, Ville, Yves, Bengoa, Joana, Ait Arkoub, Zaina, Fourrage, Cécile, Encha‐Razavi, Ferechté, Bessières, Bettina, Attié‐Bitach, Tania
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2025; Wiley
• Subjects: Abnormalities, Multiple - diagnostic imaging; Abnormalities, Multiple - genetics; Adaptor Proteins, Vesicular Transport - genetics; Anomalies; Arthrogryposis; Asymmetry; Autopsies; Birth defects; Brain stem; Central nervous system; Cerebellum; congenital disorders of glycosylation; Consanguinity; Corpus callosum; Diagnosis; Endoplasmic reticulum; Exome Sequencing; Female; Fetuses; Genetic counseling; Genomes; Glycosylation; Hereditary diseases; Histology; Humans; Hydrocephalus; Hypoplasia; Literature reviews; Male; Nose; Patients; Pedigree; Penis; Phenotype; Phenotypes; Pierre Robin Syndrome - diagnostic imaging; Pierre Robin Syndrome - genetics; Pregnancy; Prenatal Diagnosis; prenatal ultrasound; Proteins; Pulmonary arteries; Siblings; Spinal cord; Splenomegaly; Whole genome sequencing; arthrogryposis; exome sequencing; prenatal ultrasound; corpus callosum; congenital disorders of glycosylation
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.2442

Background CDG2L (MIM#614576) is an autosomal recessive multisystemic disorder due to variants in COG6 gene. Postnatal phenotypes are now well described, while prenatal presentations remain poorly investigated. Only 8 of the 28 published patients have had prenatal ultrasound anomalies reported and no one post‐mortem investigation. Methods We used whole‐exome sequencing in a consanguineous Turkish family with four siblings presenting with Pierre Robin sequence, arthrogryposis, heart malformation, splenomegaly, hydrocephaly, corpus callosum dysgenesis, brainstem, and cerebellar hypoplasia. Results We identified a novel homozygous pathogenic variant in exon 9 of COG6 (NM_020751.2): c.821del, p.(Arg274Lysfs*32). In this family, our post‐mortem study led us to describe further the prenatal phenotype of CDG2L. In addition, it permits correlating the most relevant anomalies to a maldevelopmental cascade due to a neurodegenerative process of metabolic origin, affecting the entire central nervous system including the spinal cord. Conclusion In this context of recurrence of multisystemic disease diagnosed antenatally, exome sequencing is powerful to give a precise diagnosis and allows proposing a molecular prenatal diagnosis at the following pregnancy.