HEREDITY DISORDERS OF CONNECTIVE TISSUE--CLINICAL AND MOLECULAR STUDIES

共有145名马凡综合征及相关疾病(MASS)患者 表型、二尖瓣脱垂综合征、家族性主动脉夹层) 已经在NHGRI遗传学诊所看到过。收集的临床数据 包括骨骼、眼部和心血管方面的详细信息 每名患者的临床表现。最终，我们的计划是将 纤维蛋白-1(FBN1)特异性突变的临床观察 吉恩。此外，还将分析临床数据以评估其有效性。 关于马凡综合征新诊断标准的建议。长期的 计划对未完成诊断的患者进行临床随访 标准，以确定这些患者的自然病史以及 为他们提供最佳的管理方案。共有30个新家庭(8个 散发性病例，22例(多代)甲骨-膝盖骨综合征 招募并启动了分子研究。新奇的重组事件 进一步细化了一般区间。物理测绘研究一直是 启动，并且整个NPS间隔在一系列 重叠的YAC克隆。在一部分家庭中，开角型青光眼 链接到NPS。青光眼是否代表以前未被认识到的 综合征的一个方面或由连锁基因突变(S)造成的结果，是 正在调查中。青光眼与9号染色体的关联尚未得到证实 之前报道过。为了澄清两者之间的关系 Stickler综合征的表型和潜在的基因突变，我们有 启动对26个Stickler综合征家系的临床和临床研究 分子手段。最近，有人提出了两种亚型的 粘滞综合征可以根据眼睛的严重程度来定义 调查结果。在我们研究的七个家系中，Stickler表型是 未链接到COL2A1。我们的数据表明，并不是所有患有癌症的家庭 “经典”斯蒂克勒综合征患者的COL2A1基因发生了突变。我们 建议在有足够多的家庭发现分子缺陷之前 Stickler综合征亚型应以临床表型为基础 单独的，并不是由携带突变的基因座定义的。

A total of 145 patients with Marfan syndrome and related conditions (MASS phenotype, mitral valve prolapse syndrome, familial aortic dissection) have been seen in the NHGRI Genetics Clinic. Clinical data collected included detailed information on skeletal, ocular and cardiovascular manifestations in each patient. Eventually, the plan is to correlate clinical observations with specific mutations in the fibrillin-1 (FBN1) gene. Additionally, clinical data will be analyzed to assess the validity of proposed new diagnostic criteria for Marfan syndrome. Long-term clinical follow-up is planned for patients not fulfilling the diagnostic criteria, to determine the natural history of these patients and also the optimal management scheme for them. A total of 30 new families (8 sporadic cases, 22 multigenerational) with Nail-Patella syndrome were recruited and molecular studies initiated. Novel recombination events further refined the gentic interval. Physical mapping studies have been initiated and the entire NPS interval is defined in a series of overlapping YAC clones. In a subset of families, open angle glaucoma is linked to NPS. Whether glaucoma represents a previously unrecognized aspect of the syndrome or results from mutation(s) in a linked gene, is under investigation. Linkage of glaucoma to chromosome 9 has not been reported previously. In an effort to clarify the relationship between the Stickler syndrome phenotype and underlying gene mutations, we have initiated the study of 26 Stickler syndrome families by clinical and molecular means. Recently it has been proposed that two subtypes of Stickler syndrome can be defined based on the severity of ocular findings. In seven of the families we studied, the Stickler phenotype was not linked to COL2A1. Our data demonstrate that not all families with "classical" Stickler syndrome have mutations in the COL2A1 gene. We suggest that until sufficient families with identified molecular defects are studied, Stickler syndrome subtypes be based on clinical phenotype alone and not defined by the locus carrying the mutation.