Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, Maryland, United States of America.
PLoS One. 2014 Apr 16;9(4):e94960. doi: 10.1371/journal.pone.0094960. eCollection 2014.
To investigate the clinical features and cytochrome P450 family 4 subfamily V polypeptide 2 (CYP4V2) gene mutations in 14 Chinese families with Bietti crystalline dystrophy (BCD).
Seventeen patients from 14 unrelated Chinese families with BCD were recruited for complete clinical ophthalmic examination and genetic study. The 11 exons of CYP4V2 were amplified from genomic DNA of all patients and their family members by polymerase chain reaction (PCR) and then sequenced. Exons of TIMP3 were also sequenced in BCD patient associated with choroidal neovascularization (CNV). One hundred and seventy unrelated healthy Chinese subjects were screened for mutations in CYP4V2.
All 17 patients with BCD had mutations in CYP4V2; one of these mutations was novel (c.219T>A, p.F73L) and four other mutations had been reported. The p.F73L mutation was a commonly detected mutation in our study (seven out of 34 alleles), either in the homozygous state or in the heterozygous state. Among the patients, considerable phenotypic variability was detected, both within and between families. Screening of TIMP3 did not find any mutation in the BCD patient associated with CNV.
The novel CYP4V2 c.219T>A (p.F73L) mutation may be another recurrent mutation in Chinese patients with BCD. Our study expands the mutation spectrum of CYP4V2 and characterizes novel genotype-phenotype associations in Chinese patients with BCD.
研究 14 个中国 Bietti 结晶样营养不良（BCD）家系的临床特征和细胞色素 P450 家族 4 亚家族 V 多肽 2（CYP4V2）基因突变。
从 14 个无关的中国 BCD 家系中招募了 17 名患者进行全面的眼科临床检查和遗传研究。使用聚合酶链反应（PCR）从所有患者及其家庭成员的基因组 DNA 中扩增 CYP4V2 的 11 个外显子，然后对其进行测序。与脉络膜新生血管（CNV）相关的 BCD 患者还对 TIMP3 外显子进行了测序。在 170 名无关的健康中国对照中筛选 CYP4V2 的突变。
所有 17 名 BCD 患者均存在 CYP4V2 突变；其中一种突变是新的（c.219T>A，p.F73L），另外四种突变已有报道。在我们的研究中，p.F73L 突变是一种常见的突变（34 个等位基因中有七个），无论是纯合状态还是杂合状态。在这些患者中，无论是在家族内还是家族间，均发现了相当大的表型变异性。对 TIMP3 的筛查未发现与 CNV 相关的 BCD 患者的任何突变。
新型 CYP4V2 c.219T>A（p.F73L）突变可能是中国 BCD 患者的另一个常见突变。我们的研究扩展了 CYP4V2 的突变谱，并描述了中国 BCD 患者新的基因型-表型相关性。
