ObjectiveTo identify the pathogenic genes and mutations in a Hui population family with Goldmann-Favre syndrome.MethodsA two-generation Hui population family with consanguineous marriage including 4 individuals was enrolled in this study. DNA was extracted from 4 ml peripheral venous blood of all participants. The DNA sequence was performed by Ophthalmology Gene panel sequencing through Ion PGM platform. Then the selected mutations were proved by PCR-Sanger sequencing method. Pathogenic analysis of the mutation was done by means of retrieving PubMed and related databases. And the function of mutation effect was interpreted by protein prediction software.ResultsThe sequence result showed that a novel homozygous mutation in NR2E3, c.925C＞T (p.R309W), which resulted in conversion of arginine to tryptophan at position 309 of the photoreceptor-specific retinal nuclear receptor. Parents of the proband were carriers of the heterozygous mutation. The 309 amino acid locus of NR2E3 protein product was highly conserved among species, and protein prediction softwares predicted the mutation as harmful.ConclusionThe homozygous mutation c.925C＞T (p.R309W) in NR2E3 cause Goldmann-Favre syndrome in this patient.
ObjectiveTo analyze and identify the pathogenic mutation that caused a case of child’s renal coloboma syndrome (RCS).MethodsA child with congenital cataract in the right eye and optic disc defect in the left eye and his parents with normal phenotype were included in the study. The blood of the child and his parents were captured to extract DNA and make molecular test. The possible variants were screened through NGS sequencing using the ophthalmology gene panel on illumina NextSeq 500 platform, and proved the selected PAX2 mutation by Sanger sequencing. Pathogenicity report was retrieved through PubMed and related database. Pathogenicity analysis of the candidate mutated site has careful consideration of the patient’s clinical presentations and sequencing result base on Standards and Guidelines for the Interpretation of Sequence Variants revised by ACMG. According to the results of gene diagnosis, the child was executed related clinical examinations on kidney.ResultsThe sequence result showed that a heterozygous mutation in PAX2, c.70dupG (p.V26Gfs*28), which lead to truncated protein product that terminated after 28 amino acids of the mutated site. Both of his normal parents were not carriers of the heterozygous mutation. Sanger sequencing results of the child and his parents were consistent with the NGS sequencing. The autosomal dominant disease phenotype was inferred to be caused by the heterozygous mutation of c.70dupG (p.V26Gfs*28) of PAX2 gene. Renal color Doppler ultrasound results showed the child with small renal cysts on the left and mildly separated collecting system. Renal function tests showed the child with α1 microglobulin index increased.ConclusionThe heterozygous mutation c.70dupG (p.V26Gfs*28) in PAX2 is the genetic pathogenic cause for the patient with RCS.
ObjectiveTo observe and analyze the pathogenic gene types and clinical phenotypes of Leber congenital amaurosis (LCA).MethodsA retrospective clinical study. Six patients with LCA confirmed by genetic testing and 18 family members were included in the study. The patients came from six unrelated families. The family was investigated with a specific hereditary eye disease enrichment panel which contained 463 known pathogenic genes and based on targeted exome capture technology first to indentify the potential pathogenic genes and mutations. Then the TULP1, RPGRIP1, GUCY2D pathogenic mutations were conformed by Sanger sequencing. The pathogenicity of the gene variation was searched through relevant databases and PubMed literature, and its function was explained by protein prediction software.ResultsOf the 6 patients, 3 were males and 3 were females; the age was from 3 to 33 years. Nystagmus, finger pressing eyes, photophobia, and night blindness were seen in 5 cases; electroretinogram showed 3 cases of extinction or near extinction; and 4 cases of retinopathy. The results showed patients with compound heterozygous mutation of c.1318C＞T and c.1142T＞G, homozygous mutation ofc.1318C＞T and compound heterozygous mutation of c.1153G＞A and c.1561C＞T of TULP1 in Family 1, Family 2 and Family 5, respectively. There were compound heterozygous mutations of RPGRIP1 c.391delG and c.1468-2A＞G in Family 3 and c.715delA and c.1765C＞T in Family 6, respectively. Homozygous mutation of c.3177_3178delAC of GUCY2D was found in Family 4.The parents of all six patients were carriers of corresponding heterozygous mutations.TULP1 gene c.1142T＞G, RPGRIP1 gene c.391delG, c.715delA and c.1765C＞T and GUCY2D gene c.3177_3178delAC mutations were novel mutations and unreported. The 381th amino acid locus of product protein of TULP1 gene was highly conserved among species. The protein prediction software predicted that the mutation pathogenic. The c.391delG, c.715delA and c.1765C＞T mutations of RPGRIP1 gene and c.3177_3178delAC mutation of GUCY2D gene can lead to early translation termination of their product proteins, which are pathogenic variants.ConclusionThe pathogenic mutations of TULP1, RPGRIP1 and GUCY2D genes led to LCA 15, LCA 6 and LCA 1 in six families.