Kordaß Ulrike, Schröder Carmen, Elbracht Miriam, Soellner Lukas, Eggermann Thomas
Praxis für Humangenetik, Greifswald, Germany.
Am J Med Genet A. 2015 May;167A(5):1121-4. doi: 10.1002/ajmg.a.36972. Epub 2015 Mar 28.
Molecular alterations of the GLI2 gene in 2q14.2 are associated with features from the holoprosencephaly spectrum. However, the phenotype is extremely variable, ranging from unaffected mutation heterozygotes to isolated or combined pituitary hormone deficiency, and to patients with a phenotype that overlaps with holoprosencephaly, including abnormal pituitary gland formation/function, craniofacial dysmorphisms, branchial arch anomalies, and polydactyly. Although many point mutations within the GLI2 gene have been identified, large (sub) microscopic deletions affecting 2q14.2 are rare. We report on a family with a 4.3 Mb deletion in 2q14 affecting GLI2 without any dysmorphologic features belonging to the holoprosencephaly spectrum. This family confirms the incomplete penetrance of genomic disturbances affecting the GLI2 gene. However, the family presented here is unique as none of the three identified individuals with a GLI2 deletion showed any typical signs of holoprosencephaly, whereas all patients reported so far were referred for genetic testing because at least one member exhibited holoprosencephaly and related features.
2q14.2区域GLI2基因的分子改变与全前脑谱系特征相关。然而，其表型差异极大，从不受影响的突变杂合子到孤立或合并的垂体激素缺乏，再到具有与全前脑重叠表型的患者，包括垂体腺形成/功能异常、颅面畸形、鳃弓异常和多指畸形。尽管已在GLI2基因内鉴定出许多点突变，但影响2q14.2的大（亚）显微缺失很少见。我们报告了一个家族，其2q14区域存在4.3 Mb的缺失，影响GLI2基因，但没有任何属于全前脑谱系的畸形特征。这个家族证实了影响GLI2基因的基因组干扰的不完全外显率。然而，这里呈现的家族很独特，因为三个已鉴定的携带GLI2基因缺失的个体均未表现出任何全前脑的典型体征，而迄今为止报告的所有患者都是因为至少有一名成员表现出全前脑及相关特征而被转诊进行基因检测的。
