PHENOTYPE AND ETIOLOGY OF PALLISTER/HALL SYNDROME

这项研究包括一系列表型，包括Pallister-Hall综合征，等位基因疾病Greig头多并指综合征（GCPS），McKusick-Kaufman综合征（MKS）和Bardet-Biedl综合征（BBS）。这些疾病的临床表现包括多指（趾）畸形、中枢神经系统畸形（伴或不伴精神发育迟滞和癫痫发作）、颅面畸形和内脏畸形（如肾畸形或先天性心脏缺陷）。我们通过转化方法研究这些疾病，该方法从临床开始，通过体格检查、影像学研究（包括X光片、超声、MRI和CT扫描）对表型进行仔细的临床评价。我们已经证明BBS和MKS都可以由同一基因的突变引起。PHS和GCPS是由GLI 3基因的广泛突变引起的。一种类型的突变导致PHS（3个素数截短），并且任何功能丧失突变导致GCPS。GCPS表型的严重程度，特别是精神发育迟滞和学习障碍，与突变相关。具有较大缺失的患者具有更严重的表型。

This research study encompasses a range of phenotypes that include Pallister-Hall syndrome, the allelic disorder Greig cephalopolysyndactyly syndrome (GCPS), McKusick-Kaufman syndrome (MKS), and Bardet-Biedl syndrome (BBS). The clinical manifestations of these disorders include polydactyly, central nervous system malformations (with or without mental retardation and seizures), craniofacial malformations, and visceral malformations such as renal malformations or congenital heart defects. We study these disorders by a translational approach that begins in the clinic with careful clinical evaluation of the phenotypes by physical examination, imaging studies that include radiographs, ultrasound, MRI and CT scanning. We have shown that BBS and MKS can both be caused by mutations in the same gene. PHS and GCPS are caused by a wide spectrum of mutations in the GLI3 gene. One type of mutations causes PHS (3 prime truncations) and any loss of function mutation causes GCPS. The severity of the GCPS phenotype, specifically the mental retardation and learning disability, are correlated with the mutations. Patients with larger deletions have a more severe phenotype.