title: Diagnosis of ALG12-CDG by exome sequencing in a case of severe skeletal dysplasia.
abstract: 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 theALG12gene. 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 underossification of the pubic bones. Exome sequencing was performed and two deletions, each resulting in frameshifts, were found inALG12. 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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine; One Baylor Plaza, MS BCM225, Houston, TX, 77030, U.S.A.
authors.forename: Chaya
authors.initials: C
authors.lastname: Murali
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine; One Baylor Plaza, MS BCM225, Houston, TX, 77030, U.S.A. ; Department of Structural and Computational Biology & Molecular Biophysics, Baylor College of Medicine; One Baylor Plaza, MS BCM225, Houston, TX, 77030, U.S.A.
authors.forename: James T
authors.initials: JT
authors.lastname: Lu
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine; One Baylor Plaza, MS BCM225, Houston, TX, 77030, U.S.A.
authors.forename: Mahim
authors.initials: M
authors.lastname: Jain
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine; One Baylor Plaza, MS BCM225, Houston, TX, 77030, U.S.A.
authors.forename: David S
authors.initials: DS
authors.lastname: Liu
authors.affiliation: Radiological Sciences and Pediatrics, University of California-Los Angeles School of Medicine; 550 OHRC, Los Angeles, CA 90095.
authors.forename: Ralph
authors.initials: R
authors.lastname: Lachman
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine; One Baylor Plaza, MS BCM225, Houston, TX, 77030, U.S.A.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine; One Baylor Plaza, MS BCM225, Houston, TX, 77030, U.S.A. ; Howard Hughes Medical Institute; One Baylor Plaza, MS BCM225, Houston, TX, 77030, U.S.A.
authors.forename: Brendan H
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California-Los Angeles; 550 OHRC, Los Angeles, CA 90095 ; Orthopaedic Hospital Research Center, Department of Orthopaedic Surgery, University of California-Los Angeles; 550 OHRC, Los Angeles, CA 90095.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cohn
authors.affiliation: Medical Genetics Service, Department of Pediatrics, Sainte-Justine Hospital, University of Montreal; Medical genetics service, Room 6727, Sainte-Justine Hospital, 3175, Côte-Sainte-Catherine, Montréal QC Canada H3T 1C5.
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Campeau
keywords: ALG12; ALG12-CDG; CDG-Ig; congenital disorder of glycosylation; severe skeletal dysplasia; whole exome sequencing