Autosomal Dominant Osteopetrosis (ADO) Caused by a Missense Variant in the TCIRG1 Gene.
J Clin Endocrinol Metab
; 109(7): 1726-1732, 2024 Jun 17.
Article
en En
| MEDLINE
| ID: mdl-38261998
ABSTRACT
CONTEXT Autosomal dominant osteopetrosis (ADO) is a rare genetic disorder resulting from impaired osteoclastic bone resorption. Clinical manifestations frequently include fractures, osteonecrosis (particularly of the jaw or maxilla), osteomyelitis, blindness, and/or bone marrow failure. ADO usually results from heterozygous missense variants in the Chloride Channel 7 gene (CLCN7) that cause disease by a dominant negative mechanism. Variants in the T-cell immune regulator 1 gene (TCIRG1) are commonly identified in autosomal recessive osteopetrosis but have only been reported in 1 patient with ADO. CASE DESCRIPTION Here, we report 3 family members with a single heterozygous missense variant (p.Gly579Arg) in TCIRG1 who have a phenotype consistent with ADO. Three of 5 protein prediction programs suggest this variant likely inhibits the function of TCIRG1. CONCLUSION:
This is the first description of adult presentation of ADO caused by a TCIRG1 variant. Similar to families with ADO from CLCN7 mutations, this variant in TCIRG1 results in marked phenotype variability, with 2 subjects having severe disease and the third having very mild disease. This family report implicates TCIRG1 missense mutations as a cause of ADO and demonstrates that the marked phenotypic variability in ADO may extend to disease caused by TCIRG1 missense mutations.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteopetrosis
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Linaje
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Mutación Missense
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos