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，被认为是作为一种自动隐性性状遗传的。它的特征是双侧颞部的痕迹，老年人的外表，眼睛周围的皮肤起皱，两个眼睑上没有睫毛，或者上眼睑上有多排睫毛，下眼睑上没有睫毛，嘴和下巴感觉像橡胶，眉毛急剧向上倾斜。 负责SS的基因尚未确定，SS的分子基础尚不清楚。对波多黎各Setleis患者的DNA分析未能建立与候选基因区域1 q32 -44、2 q11 -13、3q 27、11 q23-q24和13 q12以及1 p36的连锁。我们建议：1）进行全基因组扫描以识别Setleis基因位点，2）进行基因作图以细化SS基因的遗传候选区域，3）进行分子研究以解析基因的物理和遗传图谱并评估基因，以及4）识别这些患者中导致Setleis综合征的特定突变。 SS基因的鉴定可能为诊断和治疗这种疾病和其他外胚层发育不良提供工具。

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.