Genetic analysis and prenatal diagnosis in a Chinese with growth retardation, abnormal liver function, and microcephaly.

backgroundCongenital disorders of glycosylation (CDG) are a genetically heterogeneous group of disorders caused by defects in the synthesis and processing of glycoproteins. COG6-CDG is a kind of disorder caused by conserved oligomeric golgi complex 6 (COG6) deficiency. To date, only 19 patients with COG6-CDG have been reported.

methodsWe report a girl in a Chinese family with developmental delay, growth retardation, microcephaly, abnormal liver function, and hypohidrosis. Trio whole-exome sequencing was performed for this patient and her parents, and the variants identified were validated by Sanger sequencing. Prenatal diagnosis was done for this family during a subsequent pregnancy. The literature review on these patients was performed by reviewing articles published in English and Chinese.

resultsGenetic sequencing identified two novel heterozygous mutations: c.428G>T (p.S143I) and c.1843C>T (p.Q615X) in the COG6 gene, inherited from her healthy parents, respectively. A total of 11 different mutations in COG6 have been reported previously, and mutations potentially affecting splicing are the most common. The main clinical features included development delay, facial dysmorphism, growth retardation, skin abnormalities (hypohidrosis), microcephaly, abnormal brain structure, liver involvement, and recurrent infections.

conclusionOur work broadens the mutation spectrum of COG6 gene and states the importance of whole-exome sequencing in facilitating the definitive diagnosis of this disorder and prenatal diagnosis in a subsequent pregnancy.