A new DLK1 defect in a family with idiopathic central precocious puberty: elucidation of the male phenotype.
DLK1
Genetics
Mutations
Precocious puberty, molecular screening
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
10
09
2022
accepted:
19
12
2022
medline:
17
5
2023
pubmed:
29
12
2022
entrez:
28
12
2022
Statut:
ppublish
Résumé
We aimed to investigate a cohort of female and male patients with idiopathic central precocious puberty (CPP), negative for Makorin Ring Finger Protein 3 (MKRN3) defect, by molecular screening for Delta-like 1 homolog (DLK1) defects. DLK1 is an imprinted gene, whose mutations have been described as a rare cause of CPP in girls and adult women with precocious menarche, obesity and metabolic derangement. We enrolled 14 girls with familial CPP and 13 boys with familial or sporadic CPP from multiple academic hospital centers. Gene sequencing of DLK1 gene was performed. Circulating levels of DLK1 were measured and clinical and biochemical characteristics were described in those with DLK1 defects. A novel heterozygous mutation in DLK1, c.288_289insC (p.Cys97Leufs*16), was identified in a male proband, his sister and their father. Age at onset of puberty was in line with previous reports in the girl and 8 years in the boy. The father with untreated CPP showed short stature. No metabolic derangement was present in the father except hypercholesterolemia. Undetectable Dlk1 serum levels indicated the complete lack of protein production in the three affected patients. A DLK1 defect has been identified for the first time in a boy, underscoring the importance of genetic testing in males with idiopathic or sporadic CPP. The short stature reported by his untreated father suggests the need for timely diagnosis and treatment of subjects with DLK1 defects.
Identifiants
pubmed: 36577869
doi: 10.1007/s40618-022-01997-y
pii: 10.1007/s40618-022-01997-y
doi:
Substances chimiques
Ubiquitin-Protein Ligases
EC 2.3.2.27
Membrane Proteins
0
DLK1 protein, human
0
Calcium-Binding Proteins
0
MKRN3 protein, human
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1233-1240Subventions
Organisme : Università degli Studi della Campania Luigi Vanvitelli
ID : 390
Informations de copyright
© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).
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