Publication Type:

Journal Article

Source:

American Journal of Human Genetics, Volume 88, Number 5, p.608-615 (2011)

URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-79955809888&partnerID=40&md5=ee502299b6f69ce72cd40c743f8207bd

Keywords:

amino acid sequence, article, Bone Diseases, brachydactyly, case report, chondrodysplasia, cleft palate, clinical feature, Congenital, Developmental, face dysmorphia, female, Golgi Apparatus, gpapp enzyme, homozygosity, Homozygote, human, Humans, impad1 enzyme, infant, Joint Diseases, joint dislocation, Limb Deformities, male, missense mutation, Molecular Sequence Data, Mus, Mutation, newborn, nucleotide sequence, Nucleotides, phenotype, phosphatase, Phosphoric Monoester Hydrolases, priority journal, Protein Structure, Proteoglycans, Quaternary, short stature, Sulfotransferases, unclassified drug, Young Adult

Abstract:

We used whole-exome sequencing to study three individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism. Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, a Golgi-resident nucleotide phosphatase that hydrolyzes phosphoadenosine phosphate (PAP), the byproduct of sulfotransferase reactions, to AMP. The mutations affected residues in or adjacent to the phosphatase active site and are predicted to impair enzyme activity. A fourth unrelated patient was subsequently found to be homozygous for a premature termination codon in IMPAD1. Impad1 inactivation in mice has previously been shown to produce chondrodysplasia with abnormal joint formation and impaired proteoglycan sulfation. The human chondrodysplasia associated with gPAPP deficiency joins a growing number of skeletoarticular conditions associated with defective synthesis of sulfated proteoglycans, highlighting the importance of proteoglycans in the development of skeletal elements and joints. © 2011 The American Society of Human Genetics.

Notes:

cited By (since 1996)15

Cite this Research Publication

L. E. L. Ma Vissers, Lausch, Eb, Unger, Sbc, Campos-Xavier, A. Bd, Gilissen, Ca, Rossi, Ae, Del Rosario, Ma, Venselaar, Hf, Knoll, Ug, Nampoothiri, Sh, Nair, Mi, Spranger, Jb, Brunner, H. Ga, Bonafé, Ld, Veltman, J. Aa, Zabel, Bb, and Superti-Furga, Abd, “Chondrodysplasia and abnormal joint development associated with mutations in IMPAD1, encoding the Golgi-resident nucleotide phosphatase, gPAPP”, American Journal of Human Genetics, vol. 88, pp. 608-615, 2011.