Expanding the Molecular and Clinical Phenotype of SSR4-CDG.
Congenital disorders of glycosylation (CDG) are a group of mostly autosomal recessive disorders primarily characterized by neurological abnormalities. Recently, we described a single CDG patient with a de novo mutation in the X-linked gene, Signal Sequence Receptor 4 (SSR4). We performed whole-exome sequencing to identify causal variants in several affected individuals who had either an undifferentiated neurological disorder or unsolved CDG of unknown etiology based on abnormal transferrin glycosylation. We now report eight affected males with either de novo (4) or inherited (4) loss of function mutations in SSR4. Western blot analysis revealed that the mutations caused a complete loss of SSR4 protein. In nearly all cases, the abnormal glycosylation of serum transferrin was only slightly above the accepted normal cutoff range.
Human Genetics Program, Sanford - Burnham - Prebys Medical Discovery Institute, La Jolla, California.
Bobby G
BG
Ng
Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota.
Kimiyo
K
Raymond
Department of Genome Sciences, University of Washington, Seattle, Washington.
Martin
M
Kircher
Department of Pediatrics, University of Washington, Seattle, Washington.
Kati J
KJ
Buckingham
Department of Clinical Genetics, Greenwood Genetic Center, Charleston Office, North Charleston, South Caroline.
Tim
T
Wood
Department of Genome Sciences, University of Washington, Seattle, Washington.
Jay
J
Shendure
Department of Genome Sciences, University of Washington, Seattle, Washington.
Deborah A
DA
Nickerson
Department of Genome Sciences, University of Washington, Seattle, Washington.|Department of Pediatrics, University of Washington, Seattle, Washington.
Michael J
MJ
Bamshad
Human Genetics Program, Sanford - Burnham - Prebys Medical Discovery Institute, La Jolla, California.
Jonathan T S
JT
Wong
Department of Medical Genetics, University of Campinas (UNICAMP), São Paulo, Brazil.|Mendelics Genomic Analysis, São Paulo, São Paulo, Brazil.
Fabiola Paoli
FP
Monteiro
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
Brett H
BH
Graham
Department of Medical Genetics, University of Calgary, Calgary, AB, Canada.
Sheryl
S
Jackson
Department of Medical Genetics, University of Calgary, Calgary, AB, Canada.
Rebecca
R
Sparkes
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas.
Angela E
AE
Scheuerle
Department of Clinical Genetics, Greenwood Genetic Center, Charleston Office, North Charleston, South Caroline.
Sara
S
Cathey
Mendelics Genomic Analysis, São Paulo, São Paulo, Brazil.|Department of Neurology, University of São Paulo, São Paulo, Brazil.
Fernando
F
Kok
Clinical and Metabolic Genetics, Specially for Children, Austin, Texas.
James B
JB
Gibson
Human Genetics Program, Sanford - Burnham - Prebys Medical Discovery Institute, La Jolla, California.
Hudson H
HH
Freeze
D002135:Calcium-Binding Proteins / Q000235:genetics*; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D023061:Gene Order; D050172:Genes, X-Linked; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018000:Receptors, Peptide / Q000235:genetics*
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; C066973:signal sequence receptor
SSR4; carbohydrate-deficient transferrin; congenital disorders of glycosylation; signal sequence receptor 4; translocon complex