Early Clinical Diagnosis of PC1/3 Deficiency in a Patient With a Novel Homozygous PCSK1 Splice-Site Mutation.
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.
*Department of General and Transplant Surgery, Division of Pediatric Surgery †Department of Pediatrics I ‡Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria §Division of Pediatric Gastroenterology, Hepatology and Nutrition, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey.
Bettina
B
Härter
Irene
I
Fuchs
Thomas
T
Müller
Ulas Emre
UE
Akbulut
Murat
M
Cakir
Andreas R
AR
Janecke
D002478:Cells, Cultured; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D042241:Early Diagnosis; D004700:Endocrine System Diseases / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D005260:Female; D006130:Growth Disorders / Q000209:etiology / Q000517:prevention & control; D006720:Homozygote; D006801:Humans; D007223:Infant; D009154:Mutation; D009765:Obesity / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D010288:Parenteral Nutrition; D045664:Proprotein Convertase 1 / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012720:Severity of Illness Index; D012867:Skin / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014421:Turkey
D018389:Codon, Nonsense; D022821:RNA Splice Sites; D012333:RNA, Messenger; C587576:PCSK1 protein, human; D045664:Proprotein Convertase 1