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Objective:To identify the disease-causing mutation in a Chinese family with Stickler syndrome type 1.Methods:The pedigree investigation was conducted.A Chinese family with Stickler syndrome type 1 was enrolled in the Shantou International Eye Center in June 2012.Medical history collection and clinical examinations, such as vision, intraocular pressure, slit lamp microscopy and fundus, were carried out in all the included family members and the diagnosis was made by clinical experts.Total genomic DNAs were extracted from the peripheral blood samples (5 ml) obtained from 5 patients and 4 healthy members.The potential variant of the proband's father Ⅲ-5 were screened by whole exome sequencing (WES) and stepwise bioinformatic analysis.The segregation and mutation conformation of the variant was verified by Sanger sequencing.The pathogenicity of the variant was predicted by SIFT, Polyphen2, and MutationTaster.Conservation and three-dimensional structure of amino acid mutation were analyzed by multiple sequence alignment and UniProt.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center (No.EC20110310[2]-P02).Written informed consent was obtained from each subject or the guardian.Results:An autosomal dominant inherence in 39 members of 4 generations including 15 patients and 24 phenotypically normal members was found in the family.The proband (Ⅳ-4) showed high myopia, retinal detachment and strabismus in the right eye, and the left eye was blind.A patient (Ⅲ-5) showed high myopia and cataract in the right eye, atrophy in the left eye.A patient (Ⅳ-9) showed binocular high myopia.A heterozygous variation, c.1693C>T: p.Arg565Cys, within the exon 26 of COL2A1 gene was revealed in patient Ⅲ-5, which was only found in the patients and not in phenotypically normal members, indiacating co-separation in this family.The variant was predicted to be a severe damage by SIFT, Polyphen2 and MutationTaster.The amino acid mutation at position 565 was highly conservative among human, mouse, rat, bovine and Xenopus laevis, which caused the arginine to cysteine substitution at the X position in triple helix repeat region Gly-X-Y, affecting the function of fibrous protein and becoming pathogenic. Conclusions:Variant c.1693C>T: p.Arg565Cys in COL2A1 gene is disease-causing in this family and this is the first report about the variant in China.
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Objective To investigate the disease-causing mutation in a family with Leber congenital amaurosis (LCA).Methods A Chinese Han pedigree with LCA from Chaoshan area was recruited in Shantou International Eye Center in August 2011.The clinical features of the families were evaluated,including medical history,best corrected visual acuity,intraocular pressure and fundus photography.The peripheral blood sample of 5 ml was collected from each of the family members for the extraction of genomic DNA.DNA of the proband was investigated by whole exome sequencing (WES) and was filtered for function of variants and inheritance pattern.Then,Sanger sequencing was performed to confirm the WES result on all the participating subjects in the pedigree.Results There were 11 families of 3 generations in this pedigree,and 2 female LCA patients were found (Ⅱ 2 and Ⅱ4) who were sisters.The parents (Ⅰ-1 and Ⅰ-2) and children (Ⅲ-1,Ⅲ-2,Ⅲ-3 and Ⅲ-4) of the patients showed normal phenotype,suggesting an autosomal recessive pattern.The patients appeared severe visual impairment during early childhood.Ophthalmic examination showed diffuse pigmentation on the retina and attenuation of retinal artery in both patients.WES of proband revealed two compound heterozygous mutations (c.2234C ＞T,p.T745M;c.3488G＞T,p.C1163F) of the CRB1 gene.Sanger sequencing confirmed the mutations in both patients (Ⅱ-2 and Ⅲ-4),and the parents of the patients were found to carry one mutations respectively and the other subjects with normal phenotype had neither none or only one mutation.Conclusions The compound heterozygous mutation of c.2234C＞ T,p.T745M and c.3488G＞T,p.C1163F in CRB1 is responsible for LCA pathogenesis this Chinese Han pedigree.
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Objective To explore the carotid intima-media thickness and the value of uric acid in predicting the prognosis of coronary heart disease patients.Methods Using the random number table method,182 patients diagnosed with coronary heart disease were divided into two groups:group A was 92 cases of acute coronary syndrome (ACS),groups B was 90 cases of chronic stable angina,healthy check-up 90 cases as control group (group C),fasting blood test blood uric acid (UA),application of color Doppler ultrasound measurement carotid intima-media thick ness (IMT).Results Acute coronary syndrome (ACS) set of uric acid,IMT,plaque index were (428.5 ± 70.3) mmol/L,(1.58 ± 0.92) mm,(3.24 ± 1.81) and those in stable angina group were (356.4 ± 68.2) mmol/L,(1.32 ± 0.86) mm,(3.08 ± 1.62) and those of the control group were (251.2 ± 65.4) mmol/L,(0.92 ± 0.41) ram,(2.80 ± 1.18) to compare the difference was statistically significant(group A compared with group B(t =4.47,3.26,5.21,all P ＜ 0.05),group A compared with group C (t =8.23,9.36,7.48,all P ＜ 0.01);group SAP compared with control group the difference was statistically significant (t =6.34,5.26,7.12,all P ＜ 0.05);Linear correlation analysis showed that uric acid and carotid intima-media thickness were positively correlated,r value was 0.67.The ACS group soft carotid atherosclerosis plaque detection rate was 60.9％,SAP group was 26.7％ and the control group was 8.9％,the difference was statistically significant (x2 =21.60,P ＜ 0.05;x2 =69.11,P ＜ 0.01),group SAP compared with the control group,the difference was statistically significant (x2 =39.84,P ＜ 0.01).Conclusion Uric acid levels and carotid artery atherosclerosis and coronary artery disease are closely related,which can provide theoretical basis for the risk assessment and prognosis of coronary heart disease.Early intervention can prevent the occurrence of serious cardiovascular events.