Diagnosis of ALG12-CDG by exome sequencing in a case of severe skeletal dysplasia

• Main Authors: Chaya Murali, James T. Lu, Mahim Jain, David S. Liu, Ralph Lachman, Richard A. Gibbs, Brendan H. Lee, Daniel Cohn, Philippe M. Campeau
• Format: Article
• Language: English
• Published: Elsevier 2014-01-01
• Series: Molecular Genetics and Metabolism Reports
• Subjects: Congenital Disorder of Glycosylation; ALG12; CDG-Ig; ALG12-CDG; Severe skeletal dysplasia; Whole exome sequencing
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214426914000329

Congenital Disorder of Glycosylation type Ig (ALG12-CDG) is part of a group of autosomal recessive conditions caused by deficiency of proteins involved in the assembly of dolichol-oligosaccharides used for protein N-glycosylation. In ALG12-CDG, the enzyme affected is encoded by the ALG12 gene. Affected individuals present clinically with neurodevelopmental delay, growth retardation, immune deficiency, male genital hypoplasia, and cardiomyopathy. A total of six individuals have been reported in the literature. Here, we present an infant with rhizomelic short stature, talipes equinovarus, platyspondyly, and joint dislocations. The infant had marked under-ossification of the pubic bones. Exome sequencing was performed and two deletions, each resulting in a frameshift, were found in ALG12. A review of the literature revealed two infants with ALG12-CDG and a severe skeletal dysplasia, including under-ossification of cervical vertebrae, pubic bones, and knees; in addition to talipes equinovarus and rhizomelic short stature. The phenotype of the individual we describe resembles pseudodiastrophic dysplasia and we discuss similarities and differences between ALG12-CDG and pseudodiastrophic dysplasia. The differential diagnosis in selected undiagnosed skeletal dysplasias should include CDGs.