11p13 (WAGR syndrome) region |
- 3
Haplo
Score - 1
Triplo
Score
Dosage Sensitivity Summary (Region)
Dosage ID:
ISCA-37401
Curation Status:
Complete
Issue Type:
Dosage Curation -
Region
Description:
DELETION INFO:
ISCA P Value: ND EICHLER P Value: ND
OMIM: #194072
SEG DUP mediated: No
REFS: Reference 1: Jordan, et al., Nature Genetics. 1:328-332, 1992; PMID: 1302030
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
Little Evidence for Triplosensitivity
(1)
Last Evaluated:
05/24/2016
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- WAGR syndrome Monarch
HI Evidence Comments:
Contiguous gene deletions at 11p13 which contain PAX6 and WT1, at minimum, cause WAGR syndrome (Wilms tumor-aniridia-genital anomalies-retardation). Heterozygous loss of PAX6 is responsible for aniridia and heterozygous loss of WT1 is responsible for the increased risk of Wilms tumor. The presence and severity of other clinical features typically correlates with the size of the deletion. See GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1360/.
Triplosensitivity (TS) Score Details
TS Score:
1
TS Evidence Strength:
Little Evidence for Triplosensitivity (Disclaimer)
TS Published Evidence:
-
PUBMED: 23701296
Schilter et al. (2013) report a 6 year old girl with bilateral microphthalmia, congenital cataracts, glaucoma, abnormal pupil dilation, optic nerve hypoplasia, retinal detachment, borderline microcephaly, hypotonia, pituitary hypoplasia, and ADHD. She had an 877 kilobase duplication encompassing PAX6 and WT1 (hg19 coordinates: chr11:31609664-32486962). This duplication was inherited from her mother who had bilateral congenital cataracts, glaucoma, myopia, abnormal pupil dilation, corneal opacities, unilateral sensorineural hearing loss, and short stature. There was a strong maternal family history of similar clinical features but no other individuals were available for testing. Previous screening for mutations in SOX2, OTX2, PITX2, PITX3, FOXE3, and BMP4 was negative.
TS Evidence Comments:
Additionally, Palumbo et al. (PMID:24550760) report a patient with a Russell-Silver syndrome phenotype and a de novo 4.3 megabase duplication. The only ocular feature described was left convergent strabismus. Dolan et al. (PMID:21932318) reported a 5.5-5.8 megabase duplication found in the healthy brother of a patient with the reciprocal deletion. This duplication carrier was noted to have ptosis and a broad forehead but was developmentally normal at age 4 and had a normal ophthalmologic exam, renal ultrasound and echocardiogram. Additional large duplications that overlap this region and are associated with variable clinical features, including variable ocular features, are reviewed in Aalfs et al (PMID: 9415682).
At this time, there is no consistent phenotype associated with duplication of this region including only PAX6 and WT1. It is not clear if duplication of this region contributes to ocular abnormalities. If it is directly responsible for ocular abnormalities, the variable expressivity is not understood.
Genomic View
Select assembly:
(NC_000011.9)
()