A Novel PGM3 Mutation Is Associated With a Severe Phenotype of Bone Marrow Failure, Severe Combined Immunodeficiency, Skeletal Dysplasia, and Congenital Malformations.

J Bone Miner Res 2017 Sep 26;32(9):1853-1859. Epub 2017 Jun 26.

Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada.

Congenital disorders of glycosylation (CDGs) affect multiple systems and present a broad spectrum of clinical features, often including skeletal dysplasia. Exome sequencing has led to the identification of new CDG genes. Immune and skeletal phenotypes associated with mutations in PGM3, encoding a protein that converts N-acetyl-glucosamine-6-phosphate into N-acetyl-glucosamine-1-phosphate, were recently reported. Through exome sequencing, we identified a novel homozygous mutation (c.1135T>C; p.Phe379Leu) in PGM3 in two siblings with bone marrow failure, severe combined immunodeficiency, renal and intestinal malformations, and a skeletal dysplasia resembling Desbuquois dysplasia. Severe respiratory compromise secondary to lung hypoplasia and pulmonary hypertension, and intestinal obstruction led to their demise. We thus report the most severe phenotype described so far associated with PGM3 mutations. This CDG should be considered in the presence of skeletal dysplasia associated with severe immunodeficiency. © 2017 American Society for Bone and Mineral Research.

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.3173DOI Listing
September 2017
67 Reads
4 Citations
6.832 Impact Factor

Publication Analysis

Top Keywords

skeletal dysplasia
16
bone marrow
8
severe phenotype
8
failure severe
8
severe combined
8
combined immunodeficiency
8
associated severe
8
marrow failure
8
exome sequencing
8
severe
6
skeletal
5
dysplasia
5
skeletal phenotypes
4
cdg considered
4
phenotypes associated
4
associated mutations
4
mutations cdg
4
pgm3 encoding
4
mutations pgm3
4
renal intestinal
4

References

(Supplied by CrossRef)

Similar Publications