Clinical Basis Investigations into MLS/Leopard Syndrome

雀斑是一种常见的色素沉着病，继发于黑素细胞数量增加。多发性雀斑样痣综合征（MLS）是一种遗传性疾病，导致全身性雀斑样痣。MLS的其他表现可能包括发育、听觉和心血管异常。MLS的皮肤表现与LEOPARD综合征（MIM 151100）相似。包括LEOPARD综合征在内的临床表现包括：雀斑、ECG异常、眼距过远/阻塞性心肌病、肺动脉瓣狭窄、男性生殖器发育不良、生长迟缓和耳聋。MLS也属于一组遗传综合征，即雀斑样痣病。在这些疾病中，皮肤异常，如雀斑， 非皮肤异常，如家族性肿瘤和各种发育缺陷，表现为共享但可变的基础。尚未进行关于MLS或LEOPARD综合征的临床研究。临床疾病的全部范围和疾病的基本原因都不清楚。 该提案寻求支持，以培训一名年轻的研究人员进行面向患者的研究。该计划是一个三阶段的研究多颗扁豆综合征（MLS）：基因组学，临床调查，和二叉研究。如果该提案得到资助，那么研究者：（i）将寻求多颗扁豆综合征（MLS）的分子基础，并将调查MLS和LEOPARD综合征之间是否存在分子联系;（ii）将调查MLS和常见色素沉着异常之间是否存在关系，如果存在，这项研究是否可以作为新的诊断和治疗方法的基础，及（iii）将修读广泛的研究及医学伦理课程;并将获得健康科学研究、人类遗传学、分子及细胞生物技术、生物统计学及临床中心规例方面的经验。Theresa帕切科，医学博士助理教授 他致力于临床研究，专注于疾病的分子标志物（色素沉着异常）和以患者为导向的研究课题。

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.