Xp21.2 region (includes NR0B1) |
- 0
Haplo
Score - 3
Triplo
Score
Dosage Sensitivity Summary (Region)
Haploinsufficiency (HI) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
- 46,XY sex reversal 2 Monarch
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PUBMED: 22518125
Barbaro M et al. (2012) reported 3 individuals of 46,XY sex reversal in a 6 generations English family with inheritance through seven 46,XX fertile carriers of an NR0B1/DAX1 locus duplication. Another 9 healthy 46,XX females in this family also carry this duplication. The duplication has a minimal and maximal size of 679 kb and 687 kb, respectively. In addition to NR0B1, this duplication contains the MAGEB genes, CXorf21, GK and part of the 3’ region of the MAP3K7IP3 gene. The carrier mothers are all healthy.
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PUBMED: 17504899
Barbaro M et al., (2007) reported two Iranian individuals with isolated XY gonadal dysgenesis in an X-linked inheritance pattern had a NR0B1 locus duplications (637kb), including MAGEB, NR0B1, CXorf21, GK and part of the 3’ region of the MAP3K7IP3 gene. The carrier fertile mother had NR0B1 overexpression without skewed X-inactivation or impaired ovarian function. Later study in 2008 (PMID: 18384427) confirmed the healthy mother carries the same duplication. This article supports DAX1 duplication as the genetic cause of gonadal dysgenesis, even if a role for the MAGEB genes cannot be completely excluded.
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PUBMED: 20685758
Ledig S et al., (2010) reported a case (case 52) with a duplication of 729kb on DAX1/NORB1 locus including 5 other genes, MAGEB4, MAGEB1, CXorf21, GK and MAP3K7IP3 from cohort of 26 patients with 46, XY gonadal dysgenesis.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.