Ahmad N N, McDonald-McGinn D M, Dixon P, Zackai E H, Tasman W S
Research Division, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-5598, USA.
J Med Genet. 1996 Aug;33(8):678-81. doi: 10.1136/jmg.33.8.678.
Stickler syndrome is an autosomal dominant disease with ocular (severe myopia, vitreal degeneration, and retinal detachment) and other systemic manifestations (hearing loss, cleft palate, epiphyseal dysplasia, and premature osteoarthritis). As with other dominantly inherited conditions, the clinical phenotype of Stickler syndrome varies considerably. To date, all mutations have been located in the type II procollagen (COL2A1) gene. Analysis of a C-->T mutation we had identified previously, in COL2A1 gene in exon 40, in a three generation pedigree showed the loss of a cleavage site for the TaqI restriction enzyme. We designed a rapid PCR based restriction enzyme assay to detect this mutation and used it to establish the diagnosis in a neonate from the same pedigree, presenting with the first occurrence of the Pierre-Robin sequence in the family and minimal ocular findings. These results underline the potential diagnostic value of many as yet undetected DNA mutations in families affected with Stickler syndrome, since the variability of the phenotype can impede accurate diagnosis, appropriate genetic counselling, and effective intervention and prophylactic treatment for affected people.
斯-利二氏综合征是一种常染色体显性疾病，具有眼部症状（严重近视、玻璃体变性和视网膜脱离）以及其他全身症状（听力丧失、腭裂、骨骺发育异常和早发性骨关节炎）。与其他显性遗传疾病一样，斯-利二氏综合征的临床表型差异很大。迄今为止，所有突变均位于II型前胶原（COL2A1）基因中。我们对先前在一个三代家系的COL2A1基因第40外显子中鉴定出的一个C→T突变进行分析，结果显示TaqI限制性内切酶的一个切割位点缺失。我们设计了一种基于快速聚合酶链反应的限制性内切酶检测方法来检测该突变，并将其用于对来自同一家系的一名新生儿进行诊断，该新生儿出现了家族中首例皮埃尔-罗宾序列，且眼部症状轻微。这些结果强调了在受斯-利二氏综合征影响的家系中，许多尚未被发现的DNA突变具有潜在的诊断价值，因为表型的变异性可能会妨碍对患者进行准确诊断、适当的遗传咨询以及有效的干预和预防性治疗。
