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The first case of antenatal presentation in COG8‐congenital disorder of glycosylation with a novel splice site mutation and an extended phenotype
Author(s) -
Arora Veronica,
Puri Ratna Dua,
Bhai Pratibha,
Sharma Nidhish,
Bijarnia–Mahay Sunita,
Dimri Nandita,
Baijal Ashok,
Saxena Renu,
Verma Ishwar
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61030
Subject(s) - exon , phenotype , exome sequencing , splice , splice site mutation , genetics , exon skipping , biology , mutation , medicine , alternative splicing , gene
Congenital disorders of glycosylation (CDG) are an extremely rapidly growing and phenotypically versatile group of disorders. Conserved oligomeric Golgi (COG) complexes are hetero‐octameric proteins involved in retrograde trafficking within the Golgi. Seven of its eight subunits have a causal role in CDG. To date, only three cases of COG8‐CDG have been published but none in the antenatal period. We present the first case of antenatally diagnosed COG8‐CDG with facial dysmorphism and additional features such as Dandy‐Walker malformation and arthrogryposis multiplex congenita, thus expanding the phenotype of this rare disorder. Trio whole exome sequencing revealed a novel homozygous variant in COG8 , which creates a new splice site in exon 5 and protein truncation after 12 amino acids downstream to the newly generated splice site. As the mutations of the previous three patients were also identified in exon 5, it is likely to be a potential mutational hotspot in COG8 . An association between antenatally increased nuchal translucency and COG8‐CDG is also established, which would alert clinicians to its diagnosis early in gestation. It remains to be seen if this observation can be extended to other COG‐CDGs.