Primary congenital glaucoma (PCG) is one of the major diseases causing blindness in children, but its pathogenesis has remained unclear. Genetic factors play an important role in the pathogenesis of PCG. Molecular genetics of candidate genes such as CYP1B1, MYOC, LTBP2 and FOXC1 has so far been explored, but no disease-causing gene has been identified. Molecular genetic research on PCG including candidate gene screening and research strategies are reviewed here.
Animals ; DNA Mutational Analysis ; Genetic Testing ; Glaucoma ; genetics ; Humans

OBJECTIVETo study the frequency of telomerase gene (TERC and TERT) mutation in Northern Chinese patients with acquired bone marrow failure syndromes (BMFS).

METHODSDNA extracted from blood samples of 90 patients with BMFS (including AA, MDS, and PNH) and 45 normal controls from 4 northern hospitals was collected. TERC and TERT mutation analysis was performed by PCR.

RESULTSTwo TERC mutations (n37 A-->G, and n66 G-->C) and two TERT mutations \[n1870 G-->T (E/*)\]; and \[n1780 G-->T (S/I)\] were identified in 90 BMFS patients. Among them, 3 mutations were reported for the first time. One patient with TERT mutation, however, was finally diagnosed as DKC instead of acquired AA, making the incidence of telomerase gene mutation in northern Chinese people with acquired BMFS 3.4%, similar to that of the western country people.

CONCLUSIONThe incidence of telomerase gene mutation in northern Chinese people with acquired bone marrow failure syndromes is 3.4%, similar to that of the western country people.

DNA Mutational Analysis ; Humans ; Infant, Newborn ; Mutation ; Neonatal Screening

OBJECTIVE: To detect potential mutation in a large pedigree affected with preaxial polydactyly II. METHODS: With informed consent obtained, peripheral blood samples were collected from the proband, her family members as well as 100 healthy controls. Genomic DNA was extracted. The zone of polarizing activity regulatory sequence (ZRS) of the SHH gene was amplified by PCR and subjected to bi-directional Sanger sequencing. RESULTS: The pedigree had typical preaxial polydactyly II. A heterozygous C>G mutation at position 105 of the ZRS region was detected in all patients but none of the unaffected members and 100 healthy controls. CONCLUSION The heterozygous 105C>G mutation of the ZRS region probably underlies the disease in this pedigree.
DNA Mutational Analysis ; Female ; Humans ; Mutation ; Pedigree ; Polydactyly ; Thumb

OBJECTIVE: To analyze the clinical manifestation and genetic mutation of a child with tyrosinemia type I but without elevated succinylacetone. METHODS: Clinical data of the patient was collected. Tandem mass spectrometry and gas chromatography mass spectrometry were used to analyze the blood amino acid and urine organic acid component of the proband. DNA was extracted from the child and his parents and used for mutation analysis. RESULTS: The proband was of acute type, with features including hepatomegaly, jaundice, anemia and tendency of bleeding. Serum levels of Tyrosine, Methionine and Phenylalanine were 397.12 μmol/L, 896.16 μmol/L and 292.52 μmol/L, respectively, which all distinctly exceeded the normal levels. The level of phenyllactic acid and 4-hydroxyphenyl-lactic acid of proband's urine were 17.4 μmol/L and 417.0 μmol/L, respectively, which also exceeded the normal levels, but the level of succinylacetone was within the normal range. Compound heterozygous mutations of the FAH gene, namely c.634delT (p.L212Wfs*20) and c.455G>A (p.W152X), were detected in the proband, which were both predicted to be pathogenic and were inherited from her father and mother, respectively. CONCLUSION For children with tyrosinemia type I, detection of urine succinylacetone by gas phase mass spectrometry can be negative. The diagnosis of tyrosinemia type I must rely on genetic testing and/or enzymatic assaying.
DNA Mutational Analysis ; Female ; Genetic Testing ; Heptanoates ; Humans ; Male ; Tyrosinemias

OBJECTIVE: To identify pathogenic mutation in a pedigree affected with brachydactyly and obesity. METHODS: Peripheral blood sample was collected for extraction of genomic DNA. Exons capture combined with next generation sequencing (NGS) was carried out to identify potential mutation. Sanger sequencing was used to verify the results. RESULTS: NGS has identified a novel heterozygous missense mutation (c.125A>C, p.Gln42Pro) in the exon 1 of PTHLH gene. The result was verified by Sanger sequencing. The mutations was derived from his mother. His uncle and sister have also carried the same heterozygous mutation. CONCLUSION A novel mutation of the PTHLH gene has been identified in a pedigree affected with brachydactyly type E2 and obesity.
Brachydactyly ; complications ; DNA Mutational Analysis ; Humans ; Mutation ; Obesity ; complications ; Pedigree

In cancer genome studies, the annotation of newly detected oncogene/tumor suppressor gene candidates is a challenging process. We propose using concept lattice analysis for the annotation and interpretation of genes having candidate somatic mutations in whole-exome sequencing in acute myeloid leukemia (AML). We selected 45 highly mutated genes with whole-exome sequencing in 10 normal matched samples of the AML-M2 subtype. To evaluate these genes, we performed concept lattice analysis and annotated these genes with existing knowledge databases.
DNA Mutational Analysis ; Genes, Suppressor ; Genome ; Leukemia, Myeloid, Acute ; Oncogenes ; Sequence Analysis, DNA

Progressive familial intrahepatic cholestasis type I (PFIC1) is an autosomal recessive disorder caused by biallelic mutations of ATP8B1 gene, with progressive cholestasis as the main clinical manifestation. This paper reports the clinical and genetic features of a PFIC1 patient definitely diagnosed by ATP8B1 genetic analysis. The patient, a boy aged 14 months, was referred to the hospital with the complaint of jaundiced skin and sclera over 10 months. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined etiology. On physical examination, hepatosplenomegaly was discovered in addition to jaundice of the skin and sclera. The liver was palpable 4 cm below the right subcostal margin and 2 cm below the xiphoid while the spleen 2 cm below the left subcostal margin. The liver function test revealed elevated levels of serum total bile acids, bilirubin, and transaminases; however, the γ-glutamyl transferase level was normal. The diagnosis was genetic cholestasis of undetermined origin. At the age of 1 year and 8 months, a Roux-en-Y cholecystocolonic bypass operation was performed, and thereafter the jaundice disappeared. At 5 years and 1 month, via whole genome sequencing analysis and Sanger sequencing confirmation, the boy was found to be a homozygote of mutation c.2081T>A(p.I694N) of ATP8B1 gene, and thus PFIC1 was definitely diagnosed. The boy was followed up until he was 6 years, and jaundice did not recur, but the long-term outcome remains to be observed.
Adenosine Triphosphatases ; genetics ; Cholestasis, Intrahepatic ; genetics ; DNA Mutational Analysis ; Humans ; Infant ; Male ; Mutation ; Sequence Analysis, DNA

Begomoviruses are single-stranded DNA viruses and cause severe diseases in major crop plants worldwide. Based on current genome sequence analyses, we found that synonymous codon usage variations in the protein-coding genes of begomoviruses are mainly influenced by mutation bias. Base composition analysis suggested that the codon usage bias of AV1 and BV1 genes is significant and their expressions are high. Fourteen codons were determined as translational optimal ones according to the comparison of codon usage patterns between highly and lowly expressed genes. Interestingly the codon usages between begomoviruses from the Old and the New Worlds are apparently different, which supports the idea that the bipartite begomoviruses of the New World might originate from bipartite ones of the Old World, whereas the latter evolve from the Old World monopartite begomoviruses.
Begomovirus ; genetics ; Biological Evolution ; Chromosome Mapping ; Codon ; genetics ; DNA Mutational Analysis ; DNA, Viral ; genetics ; Evolution, Molecular

OBJECTIVE: To determine the frequencies of deafness gene mutations among patients with non-syndromic hearing loss (NSHL) from northern Jiangsu province. METHODS: A total of 117 patients with NSHL were enrolled. The coding region of GJB2 gene, IVS7-2A>G and 2168A>G mutations of SLC26A4 gene, and 1555A>G and 1494C>T mutations of mitochondrial DNA 12S rRNA were subjected to Sanger sequencing. Patients in whom no mutation was detected were further tested by targeted gene capture and high-throughput sequencing. RESULTS: Among the 117 patients, 86 (73.50%) were found to carry mutations. GJB2 gene mutations were found in 61 patients (52.14%), including 22 (18.80%) with homozygous mutations and 39 (33.33%) with heterozygous mutations. SLC26A4 gene mutations were found in 19 patients (16.24%), including 4 (3.42%) with homozygous mutations and 15 with heterozygous mutations (14.53%). Mitochondrial 12S rRNA gene mutation was found in 6 patients (5.13%). Targeted gene capture and high-throughput sequencing of 8 patients identified 4 further cases, including 1 with RDX gene 129_130del and 76_79del compound heterozygous mutations, 1 with OTOF gene 1274G>C homozygous mutation, 1 with SLC26A4 gene 919-2A>G and IVS16-6G>A compound heterozygous mutation, and 1 with SLC26A4 gene 919-2A>G and A1673T compound heterozygous mutation. CONCLUSION The frequency of mutation among patients with NSHL from north Jiangsu was 73.50%, and GJB2 gene was most commonly mutated.
China ; Connexins ; DNA Mutational Analysis ; DNA, Mitochondrial ; Hearing Loss ; genetics ; Humans ; Membrane Proteins ; Mutation ; Sulfate Transporters