IDENTIFYING THE SETLEIS SYNDROME GENE DEFECT

描述（由申请人提供）：本提案的主要目的是确定导致Setleis综合征（SS）的基因突变。SS是外胚层发育不良的一种形式，被认为是作为自膜隐性性状遗传的。它的特征是双侧颞纹，老狮子样的外观，眼睛周围的皮肤起皱，上下眼睑没有睫毛或上眼睑有多排睫毛，下眼睑没有睫毛，嘴巴和下巴摸起来像橡胶一样，眉毛急剧向上倾斜。致病基因尚未确定，致病分子基础也不清楚。波多黎各Setleis患者的DNA分析未能与候选基因区域1q32-44、2q11-13、3q27、11q23-q24、13q12和1p36建立连锁关系。我们建议：1)进行全基因组扫描，以确定Setleis基因位点；2)进行基因定位，以完善SS基因的遗传候选区域；3)进行分子研究，以解决该基因的物理和遗传图谱并评估基因；4)确定导致这些患者Setleis综合征的特定突变。SS基因的鉴定可为该病及其他外胚层发育不良的诊断和治疗提供工具。

DESCRIPTION (provided by applicant): The primary objective of this proposal is to identify the genetic mutation(s) responsible for Setleis Syndrome (SS). SS is a form of ectodermal dysplasia believed to be inherited as an automosal recessive trait. It is characterized by bilateral temporal marks, an aged leonine appearance, puckered skin about the eyes, absent eyelashes on both lids or multiple rows on the upper lids and none on the lower lids, a mouth and chin that feels rubbery, and eyebrows that slant sharply upward. The gene responsible for SS has not been identified and the molecular basis for SS is not known. DNA analysis of Puerto Rican Setleis patients failed to establish linkage with candidate gene regions 1q32-44, 2q11-13, 3q27, 11q23-q24 and 13q12 and 1p36. We propose to: 1) make a genome-wide scan to identify the Setleis gene locus, 2) do gene mapping in order to refine the genetic candidate region for the SS gene, 3) engage in molecular studies to resolve the physical and genetic map of the gene and evaluate the genes and 4) identify the specific mutation responsible for Setleis Syndrome in these patients. The identification of the SS gene could lead to tool s for the diagnosis and treatment of this condition and other ectodermal dysplasias.