Genotype-Phenotype Correlations in Central Precocious Puberty Caused by MKRN3 Mutations.
J Clin Endocrinol Metab
; 106(4): 1041-1050, 2021 03 25.
Article
en En
| MEDLINE
| ID: mdl-33383582
ABSTRACT
CONTEXT Loss-of-function mutations of makorin RING finger protein 3 (MKRN3) are the most common monogenic cause of familial central precocious puberty (CPP). OBJECTIVE:
To describe the clinical and hormonal features of a large cohort of patients with CPP due to MKRN3 mutations and compare the characteristics of different types of genetic defects.METHODS:
Multiethnic cohort of 716 patients with familial or idiopathic CPP screened for MKRN3 mutations using Sanger sequencing. A group of 156 Brazilian girls with idiopathic CPP (ICPP) was used as control group.RESULTS:
Seventy-one patients (45 girls and 26 boys from 36 families) had 18 different loss-of-function MKRN3 mutations. Eight mutations were classified as severe (70% of patients). Among the 71 patients, first pubertal signs occurred at 6.2â ±â 1.2 years in girls and 7.1â ±â 1.5 years in boys. Girls with MKRN3 mutations had a shorter delay between puberty onset and first evaluation and higher follicle-stimulating hormone levels than ICPP. Patients with severe MKRN3 mutations had a greater bone age advancement than patients with missense mutations (2.3â ±â 1.6 vs 1.6â ±â 1.4 years, Pâ =â .048), and had higher basal luteinizing hormone levels (2.2â ±â 1.8 vs 1.1â ±â 1.1 UI/L, Pâ =â .018) at the time of presentation. Computational protein modeling revealed that 60% of the missense mutations were predicted to cause protein destabilization.CONCLUSION:
Inherited premature activation of the reproductive axis caused by loss-of-function mutations of MKRN3 is clinically indistinct from ICPP. However, the type of genetic defect may affect bone age maturation and gonadotropin levels.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pubertad Precoz
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Ubiquitina-Proteína Ligasas
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2021
Tipo del documento:
Article
País de afiliación:
Brasil