Yu Yinhui, Qiu Peijin, Zhu Yanan, Li Jinyu, Wu Menghan, Zhang Buyi, Yao Ke
Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, No.88 Jiefang Rd, Hangzhou, 310009, China.
Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, China.
BMC Ophthalmol. 2015 Oct 13;15:131. doi: 10.1186/s12886-015-0121-0.
To investigate the molecular defects in a four-generation Chinese pedigree affected with Thiel-Behnke corneal dystrophy (TBCD). And to further study the relationship between genetic mutation and clinical manifestations.
Individuals of the pedigree were recruited for extensive ophthalmic examinations. Histological studies of two corneal buttons obtained from lamellar keratoplasty were conducted. Peripheral blood was collected in EDTA for genomic DNA isolation from leukocytes of all affected and unaffected members. All 17 exons of the TGFBI gene were screened for mutations by polymerase chain reaction and direct DNA sequencing.
Clinical examinations revealed a typical pattern of honeycomb-like TBCD. Histopathology study demonstrated eosinophilic deposits that were congo-red-positive and did not stain with periodic acid Schiff or Masson's trichrome. Genetic analysis disclosed a heterozygous p. Arg555Trp mutation resulted from a missense c. 1663C > T nucleotide change in exon 12 of TGFBI gene in all affected members. Morever, a second rare variant in exon 6 of the TGFBI gene (p. Arg257Trp) also cosegregated within this family and has been confirmed to be a single nucleotide polymorphism (SNP) not previously reported.
The p. Arg555Trp mutation of the TGFBI gene was associated with TBCD, which revealed a novel phenotype-genotype correlation within the mutational spectrum of phenotypically diverse corneal dystrophies.
研究一个患有蒂尔-贝恩克角膜营养不良（TBCD）的四代中国家系中的分子缺陷。并进一步研究基因突变与临床表现之间的关系。
招募该家系成员进行全面的眼科检查。对从板层角膜移植术中获取的两个角膜组织块进行组织学研究。采集外周血，用乙二胺四乙酸（EDTA）抗凝，从所有患病和未患病成员的白细胞中提取基因组DNA。通过聚合酶链反应和直接DNA测序对TGFBI基因的所有17个外显子进行突变筛查。
临床检查显示出典型的蜂窝状TBCD模式。组织病理学研究显示嗜酸性沉积物，刚果红染色阳性，高碘酸希夫染色或马松三色染色不着色。基因分析发现，所有患病成员的TGFBI基因第12外显子发生错义c.1663C>T核苷酸改变，导致杂合p.Arg555Trp突变。此外，TGFBI基因第6外显子中的另一个罕见变异（p.Arg257Trp）也在该家族中共同分离，并且已被确认为一个先前未报道的单核苷酸多态性（SNP）。
TGFBI基因的p.Arg555Trp突变与TBCD相关，这在表型多样的角膜营养不良突变谱中揭示了一种新的表型-基因型相关性。
