A new case of pcsk1 pathogenic variant with congenital proprotein convertase 1/3 deficiency and literature review

TitreA new case of pcsk1 pathogenic variant with congenital proprotein convertase 1/3 deficiency and literature review
Type de publicationArticle de revue
AuteurPépin, Lucie, Colin, Estelle , Tessarech, Marine, Rouleau, Stéphanie, Bouhours-Nouet, Natacha, Bonneau, Dominique , Coutant, Régis
EditeurOxford University Press (OUP)
TypeArticle scientifique dans une revue à comité de lecture
Année2019
LangueAnglais
Date1er Avril 2018
Numéro4
Pagination985-993
Volume104
Titre de la revueThe Journal of clinical endocrinology & metabolism
ISSN1945-7197
Résumé en anglais

Issue: To report a homozygous pathogenic variant in PCSK1 in a boy affected with proprotein convertase 1/3 (PC1/3) deficiency.

Case description and literature review: A male infant born to consanguineous Turkish parents presented in the first week of life with transient central diabetes insipidus, watery diarrhea, micropenis due to hypogonadotropic hypogonadism and GH deficiency, and transient asymptomatic hypoglycemia. Further endocrine defects gradually appeared, including central hypothyroidism and mild central hypocortisolism (at 1 yr), central diabetes insipidus that reappeared progressively (at 2.5 yr), and obesity (at 2 yr). Whole exome sequencing revealed a homozygous nonsense pathogenic variant (NM_000439.4) c. 595 C>T in exon 5 of PCSK1, not yet reported in cases of proprotein convertase 1/3 (PC1/3) deficiency. To date, 26 cases of PC1/3 deficiency have been reported in the literature. All individuals had early and severe malabsorptive diarrhea and 83% had polyuria-polydipsia syndrome (before 5 yr). Most (79%) had early-onset obesity. Various endocrine disorders were present, including growth hormone deficiency (44%), mild central hypothyroidism (56%), central hypogonadism (44%), central hypocortisolism (57%), and postprandial hypoglycemia (52%). When described (n=15), proinsulin levels were consistently high: between 8 and 154 times the upper limit of normal (mean 74).

Conclusion: We described a homozygous nonsense pathogenic variant (NM_000439.4) c. 595 C>T in exon 5 of PCSK1 in a boy with congenital proprotein convertase 1/3 deficiency. Elevated proinsulin could be useful in the diagnosis of this condition.

URL de la noticehttp://okina.univ-angers.fr/publications/ua18152
DOI10.1210/jc.2018-01854
Lien vers le document

https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/jc.20...

Titre abrégéJ. Clin. Endocrinol. Metab.
Identifiant (ID) PubMed30383237