先天性无虹膜及相关眼病的临床及基因研究眼科学专业论文.docxVIP

中国医学科学院北京协和医学院 中国医学科学院北京协和医学院 硕上学位论文 结论：无虹膜及其相关眼病大多严重影响患者视力，多种眼部结构异常可合并 存在；本研究的15个家系中，11个家系为PAX6基因缺陷导致，证实其在眼部发育 异常中有重要地位；在眼部发育异常中，同样的致病基因及突变可引起不同的临床 表型，故基因型与表型的联系值得进一步探讨。 【关键词】无虹膜；PAX6；前节发育异常；基因突变 万方数据 AbstractPurpose Abstract Purpose To analyze the clinical features of aniridia and other developmental eye diseases· And identify the causal genes and mutations，aiming to study the correlation of genotypes and phenotypes． Methods 8 aniridia pedigrees and 7 pedigrees with other developmental anomalies(in。 cluding Anterior Segment Dysgenesis，Microphthalmia and Microcornea)diagnosed in the clinic during 20 1 0 to 20 1 6 were collected retrospectively．Medical history and family his_ tory were recorded，the patients were performed with ophthalmic examinations and optical coherence tomography(OCT)．Venous blood(5 m1)from the patients and relatives were collected and extracted into genomic DNA．For the anirdia patients，PAX6 gene was am- plified and Sanger sequencing was performed．Next。generation sequencing was pertormed on the patients with other developmental eye diseases．For the samples we couldn’t locate the causal mutation via Sanger sequencing，we performed MLPA(PAX6)test to detect large deletions／duplications．Then segregation was performed among the pedigrees to further confirm the causal mutation． Results 23 patients(including the probands and affected relatives)from 1 5 pedigrees were collected，among them were 1 1 patients with anirdia in 8 pedigrees and 1 2 patients with other developmental eye diseases in 7 pedigrees． 1．Clinical manifestations：(1)7 aniridia pedigrees inherited in the autosomal dominant fADl fashion and 1 case was sporadic．The 1 1 aniridia patients were all bilateral affected， among the 22 affected eyes，the visual acuity(VA)ranged from 0．O l to 0．4 with the median VA 0．1．AU the patients had nystagmus，9(8 1．8％)patients’iris were complete aplasia，2 f1 8．2％)patients’were partial aplasia．2(1 8．2％)patients were associated with bilateral ptosis．4 patients ha