A patient with a mild holoprosencephaly spectrum phenotype and heterotaxy and a 1.3 Mb deletion encompassing GLI2.

Am J Med Genet A 2012 Jan 21;158A(1):166-73. Epub 2011 Nov 21.

Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.

Loss-of-function mutations of GLI2 are associated with features at the mild end of the holoprosencephaly spectrum, including abnormal pituitary gland formation and/or function, and craniofacial abnormalities. In addition patients may have branchial arch anomalies and polydactyly. Large, microscopically visible, interstitial deletions spanning 2q14.2 have been reported in patients with multiple congenital anomalies and intellectual disability. We report here on a patient with a mild holoprosencephaly spectrum phenotype (bilateral cleft lip and palate and abnormal pituitary gland formation with panhypopituitarism) and normal psychomotor development, who was found to carry a 1.3 Mb submicroscopic heterozygous deletion in 2q14.2, encompassing the GLI2 gene. We review the genotype and phenotype of previously published probands with GLI2 aberrations. Our findings confirm the association of haploinsufficiency of GLI2 and mild HPE spectrum features. Consistent with prior reports, we observed incomplete penetrance of the deletion in the family, illustrating the multifactorial etiology of holoprosencephaly spectrum features. In addition to the holoprosencephaly spectrum features, the proband had heterotaxy of the abdominal organs. Mutations in the known heterotaxy genes (NODAL, ZIC3 and CFC1) were excluded. The deletion contains five genes, in addition to GLI2, including the EPB4.1l5 gene. Based on findings in Epb4.1l5 mutant mice we hypothesize that Epb4.1l5 is a candidate gene for the heterotaxy observed in the proband.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.34350DOI Listing
January 2012

Publication Analysis

Top Keywords

holoprosencephaly spectrum
20
mild holoprosencephaly
12
spectrum features
12
pituitary gland
8
encompassing gli2
8
spectrum phenotype
8
abnormal pituitary
8
gland formation
8
patient mild
8
gli2
6
spectrum
6
holoprosencephaly
5
nodal zic3
4
13 mb submicroscopic
4
carry 13 mb
4
psychomotor development
4
normal psychomotor
4
genes nodal
4
development carry
4
submicroscopic heterozygous
4

Similar Publications