Clinical Basis Investigations into MLS/Leopard Syndrome

雀斑样色素是一种常见的色素沉着，继发于数量增多的黑素细胞。多发性雀斑综合症(MLS)是一种遗传性疾病，可导致全身性雀斑。MLS的其他表现可能包括发育、听觉和心血管异常。MLS与皮肤表现类似于豹子综合征(MIM 151100)。包括豹综合征在内的临床表现包括：雀斑、心电异常、眼球过长/阻塞性心肌病、肺动脉瓣狭窄、男性生殖器异常、生长迟缓和耳聋。MLS也属于一组遗传综合征，即扁桃体增多症。在这些疾病中，皮肤异常，如扁桃体，和 非皮肤异常，如家族性肿瘤和不同的发育缺陷，表现在共同但不同的基础上。目前还没有关于MLS或豹子综合征的临床研究。既不知道临床疾病的全部范围，也不知道疾病的基本原因。 这项提议寻求支持，以培训一名年轻的研究人员进行以患者为导向的研究。该提案是对多发性扁豆素综合征(MLS)的三个阶段的研究：基因组学、临床研究和定向研究。如果该提案获得资助，那么研究人员：(I)将寻求多发性扁桃体综合征(MLS)的分子基础，并将调查MLS和豹子综合征之间是否存在分子联系；(Ii)将调查MLS与常见色素异常之间是否存在联系，如果存在，是否可以将这项研究用作新的诊断和治疗方法的基础；(Iii)将在研究和医学伦理学方面开展广泛的课程工作；并将获得健康科学研究、人类遗传学、分子和细胞生物技术、生物统计学和临床中心监管方面的经验。特蕾莎·帕切科，医学博士，助理教授 皮肤科博士，致力于临床研究，专注于疾病的分子标记物(色素异常)和以患者为导向的研究主题。

Lentigines are common pigmentary by hyperpigmentation secondary to an increased number of melanocytes. Multiple Lentigines Syndrome (MLS) is an inherited disease that results in generalized lentigines. Other manifestations of MLS may include developmental, auditory, and cardiovascular abnormalities. MLS is associated with skin findings phenotypically similar to those in the LEOPARD syndrome (MIM 151100). The clinical manifestations, which encompass the LEOPARD syndrome, include: Lentigines, ECG abnormalities, Ocular hypertelorism/Obstructive cardiomyopathy, Pulmonary valve stenosis, Abnormalities of genitalia in males, Retardation of growth, and Deafness. MLS also belongs to a group of genetic syndromes, the lentiginoses disorders. In these disorders, cutaneous abnormalities, such as lentigines, and non-cutaneous abnormalities, such as familial neoplasias and diverse developmental defects, manifest on a shared but variable basis. No clinical research studies on MLS or LEOPARD syndrome have been conducted. Neither the full extent of the clinical disease nor the basic cause of the disease is known. This proposal seeks support to train a young investigator in patient-oriented research. The proposal is a three-phase study of Multiple Lentigines Syndrome (MLS): genomics, clinical investigation, and diadactic study. If the proposal is funded, then the investigator: (i) will pursue a molecular basis for the Multiple Lentigines Syndrome (MLS) and will investigate whether a molecular link exists between MLS and LEOPARD Syndrome; (ii) will investigate whether a relationship exists between MLS and common pigmentation anomalies and, if so, whether this research can be used as the basis for new diagnostic and therapeutic methodologies, and (iii) will pursue extensive coursework in research and medical ethics; and will obtain experience with health sciences research, human genetics, molecular and cellular biological techniques, biostatistics, and clinical center regulations. Theresa Pacheco, M.D. is an Assistant Professor of Dermatology and is committed to a career in clinical research with an focus on molecular markers of disease (pigmentation anomalies) and patient-oriented research topics.