Variant "TBX2:c.641A-G(p.N214S)"
Search result: 1 record
Variant information
Gene:
Variant:
TBX2:c.641A-G(p.N214S) 
dbSNP ID:
no data 
GWAS trait:
no data 
Modifier statisitcs
Record:
Disorder:
Reference:
Effect type:
Expressivity(1)  
Modifier effect:
Altered endocrine values(1)  
Detail:
  • Target disease:
    Effect type:
    Expressivity 
    Modifier effect:
    Altered endocrine values 
    Evidence:
    Assessment of genotype–phenotype associations and gene activity study 
    Effect:
    TBX2 is a possible modifier of gonadal development in patients with NR5A1 mutations.
    Reference:
    Title:
    New NR5A1 mutations and phenotypic variations of gonadal dysgenesis.
    Species studied:
    Human
    Abstract:
    Mutations in NR5A1 have been reported as a frequent cause of 46,XY disorders of sex development (DSD) associated to a broad phenotypic spectrum ranging from infertility, ambiguous genitalia, anorchia to gonadal dygenesis and female genitalia. Here we present the clinical follow up of four 46,XY DSD patients with three novel heterozygous mutations in the NR5A1 gene leading to a p.T40P missense mutation and a p.18DKVSG22del nonframeshift deletion in the DNA-binding domain and a familiar p.Y211Tfs*83 frameshift mutation. Functional analysis of the missense and nonframeshift mutation revealed a deleterious character with loss of DNA-binding and transactivation capacity. Both, the mutations in the DNA-binding domain, as well as the familiar frameshift mutation are associated with highly variable endocrine values and phenotypic appearance. Phenotypes vary from males with spontaneous puberty, substantial testosterone production and possible fertility to females with and without Müllerian structures and primary amenorrhea. Exome sequencing of the sibling's family revealed TBX2 as a possible modifier of gonadal development in patients with NR5A1 mutations.