Early Clinical Diagnosis of PC1/3 Deficiency in a Patient With a Novel Homozygous PCSK1 Splice-Site Mutation.

Abstract

Autosomal recessive proprotein convertase 1/3 (PC1/3) deficiency, caused by mutations in the PCSK1 gene, is characterized by severe congenital malabsorptive diarrhea, early-onset obesity, and certain endocrine abnormalities. We suspected PC1/3 deficiency in a 4-month-old girl based on the presence of congenital diarrhea and polyuria. Sequencing the whole coding region and splice sites detected a novel homozygous PCSK1 splice-site mutation, c.544-2A>G, in the patient. The mutation resulted in the skipping of exon 5, the generation of a premature termination codon, and nonsense-mediated PCSK1 messenger ribonucleic acid decay, which was demonstrated in complementary DNA derived from fibroblasts.

• Authors: Bettina Härter, Irene Fuchs, Thomas Müller, Ulas Emre Akbulut, Murat Cakir, Andreas R Janecke
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 62 Issue 4 Pg. 577-80 (Apr 2016) ISSN: 1536-4801 [Electronic] United States
• PMID: 26488123 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Nonsense
• RNA Splice Sites
• RNA, Messenger
• PCSK1 protein, human
• Proprotein Convertase 1

Topics

• Cells, Cultured
• Codon, Nonsense
• DNA Mutational Analysis
• Early Diagnosis
• Endocrine System Diseases (diagnosis, genetics, physiopathology, therapy)
• Female
• Growth Disorders (etiology, prevention & control)
• Homozygote
• Humans
• Infant
• Mutation
• Obesity (diagnosis, genetics, physiopathology, therapy)
• Parenteral Nutrition
• Proprotein Convertase 1 (chemistry, deficiency, genetics, metabolism)
• RNA Splice Sites
• RNA Stability
• RNA, Messenger (chemistry, metabolism)
• Severity of Illness Index
• Skin (enzymology, metabolism, pathology)
• Treatment Outcome
• Turkey