Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompa...

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Bibliographic Details
Published in:Molecular genetics and metabolism 2013-09, Vol.110 (1-2), p.191-194
Main Authors: Frank, Graeme R., Fox, Joyce, Candela, Ninfa, Jovanovic, Zorica, Bochukova, Elena, Levine, Jeremiah, Papenhausen, Peter R., O'Rahilly, Stephen, Farooqi, I. Sadaf
Format: Article
Language:English
Subjects:
Alleles
Brief Communication
Child, Preschool
Diabetes insipidus
Diabetes Insipidus - complications
Diabetes Insipidus - genetics
Diabetes Insipidus - pathology
Endocrine System Diseases - complications
Endocrine System Diseases - genetics
Endocrine System Diseases - pathology
Heterozygote
Humans
Infant
Mutation
Obesity
Obesity - complications
Obesity - genetics
Obesity - pathology
Obesity, Morbid - complications
Obesity, Morbid - genetics
Obesity, Morbid - pathology
Osmoregulation - genetics
Phenotype
Polymorphism, Single Nucleotide
Prohormones
Proprotein Convertase 1 - deficiency
Proprotein Convertase 1 - genetics
Proprotein Convertases - genetics
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Summary:Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation. •We identify a fourth patient with PCSK1 deficiency.•The null phenotype of PCSK1 deficiency includes obesity and neuroendocrine abnormalities.•We extend the clinical phenotype to include central diabetes insipidus, as well as severe obesity and impaired prohormone processing.
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2013.04.005