Novel CYP4V2 mutations associated with Bietti crystalline corneoretinal dystrophy in Chinese patients

AIM: To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy（BCD） and to provide clinical features of these patients. BCD is a rare monogenic autosomal recessively inherited disorder characterized by the presence of crystals in the retina and retinal pigment epithelium atrophy. Mutations in the CYP4V2 gene have been found to be causative for BCD.METHODS: Ophthalmic examinations were carried out in the affected individuals. Peripheral blood samples were collected and genomic DNA was extracted. All exons and flanking intronic regions of the CYP4V2 gene were amplified with polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms.RESULTS: Fundus examination revealed the presence of tiny yellowish-sparkling crystals at the posterior pole of the fundus and atrophy of the retinal pigment epithelium in all patients. Choroid neovascularization was noted in one patient. Five different CYP4V2 mutations were identified, including two missense mutations（p.F73 L,p.R400H）, two splice site mutations（c.802-8810del17ins GC, c.1091-2A 】G）, and one single base-pair deletion（p.T479 Tfs X7 or c.1437 del C）. The two splice site mutations were identified in three of the patients with BCD. Mutation p.T479 Tfs X7 was a novel mutation not observed in any of 100 ethnically matched control chromosomes.CONCLUSION: Mutation c.802-8810del17ins GC and c.1091-2A】G are common mutations in Chinese patientswith BCD. Our results expand the allelic heterogeneity of BCD.

Relationship of familial cytochrome P450 4V2 gene mutation with liver cirrhosis:A case report and review of the literature

BACKGROUND Many genetic and metabolic diseases affect the liver,but diagnosis can be difficult because these diseases may have complex clinical manifestations and diverse clinical patterns.There is also incomplete clinical knowledge of these many different diseases and limitations of current testing methods.CASE SUMMARY We report a 53-year-old female from a rural area in China who was hospitalized for lower limb edema,abdominal distension,cirrhosis,and hypothyroidism.We excluded the common causes of liver disease(drinking alcohol,using traditional Chinese medicines,hepatitis virus infection,autoimmunity,and hepatolenticular degeneration).When she was 23-years-old,she developed night-blindness that worsened to complete blindness,with no obvious cause.Her parents were first cousins,and both were alive.Analysis of the patient’s family history indicated that all 5 siblings had night blindness and impaired vision;one sister was completely blind;and another sister had night-blindness complicated with cirrhosis and subclinical hypothyroidism.Entire exome sequencing showed that the patient,parents,and siblings all had mutations in the cytochrome P450 4V2gene(CYP4V2).The CYP4V2 mutations of the parents and two sisters were heterozygous,and the others were homozygous.Two siblings also had heterozygous dual oxidase activator 2(DUOXA2) mutations.CONCLUSION Mutations in the CYP4V2 gene may affect lipid metabolism and lead to chronic liver injury,fibrosis,and cirrhosis.