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Objective To report 2 pedigrees of early - onset familial Alzheimer's disease (EOFAD) caused by PSEN1 gene mutation, review previous studies and summarize the PSEN1 gene mutation sites, clinical presentation and genotype characteristics of EOFAD in China. Methods and Results The clinical data of 2 pedigrees with EOFAD from Beijing Tiantan Hospital, Capital Medical University were collected. Genomic DNA from peripheral venous blood of the proband was screened. Search the reported Chinese cases of EOFAD caused by PSEN1 gene mutation. In the Case 1 family, there were 3 members with memory loss, including the proband, onset at the age of 45. His head MRI showed mild atrophy of the cerebral cortex and bilateral hippocampus. A c.488A > G (p.His163Arg) pathogenic mutation in the exon 6 of PSEN1 gene was found, proving the diagnosis. In the Case 2 family, there were 6 members with memory and working competence loss, including the proband, onset at the age of 42. Head MRI showed whole cerebral cortical atrophy and bilateral hippocampal atrophy, obviously on the left side. A c. 344A > G (p. Tyr115Cys) pathogenic mutation in the exon 5 of PSEN1 gene was found, proving the diagnosis. A total of 40 cases (including this 2 cases) of EOFAD patients caused by PSEN1 gene mutation in China were enrolled. Thirty-eight pathogenic mutation sites were reported. The age of onset ranged from 21 to 62 years old, and the course of disease ranged from 4 to 10 years. About 87.50% (35/40) of the patients' onset manifestation was progressive memory loss and then rapidly with multiple cognitive domains involved. Some patients manifested with extrapyramidal symptoms, epilepsy or ear symptoms. Conclusions c.488A > G and c.344A > G mutations in the PSEN1 gene were identified to cause EOFAD, and c.344A > G mutation is the first report in China. EOFAD occurs early and progresses rapidly, and sometimes the initial symptoms may be atypical. Therefore, gene detection plays an important role in the diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Summary: Compound epidermal growth factor receptor (EGFR) mutations are defined as double or multiple independent mutations of the EGFR tyrosine kinase domain (TKD), in which an EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutation is identified together with a mutation of unclarified clinical significance. Lung adenocarcinoma with compound EGFR mutation shows poor clinical response to EGFR-TKIs. Kobayashi et al. reported a non-small-cell lung cancer (NSCLC) patient whose tumor had EGFR exon21 L858R/A871G mutation presented rapid disease progression to erlotinib. However, in this case, we present an EGFR exon21 L858R/A871G mutation patient exerted significant benefit to icotinib, another first-generation EGFR-TKI, indicating that different EGFR-TKIs have diversiform sensitive sites and therapeutic effects, consistent mutation sites might achieve heterogeneous benefits from different EGFR-TKIs. Our case report provides promising EGFR-TKI for clinical treatment with EGFR exon21 L858R/A871G mutation in NSCLC. More dedicated efforts are needed to clarify their biologic effects on disease course and drug responsiveness. [ABSTRACT FROM AUTHOR]

Conclusions: The mutation c.508_511dup in GJB2 gene has been incorrectly named as other mutations. It is essential to standardize mutation nomenclature to describe complex mutations. Objectives: This paper aimed to verify a series of patients with the frame-shift mutation c.508_511dup in the GJB2 gene and review the literature on related mutations. Methods: All the included patients with non-syndromic hearing loss (NSHL) carried the 504insAACG or c.508_511dup mutation of the GJB2 gene in the present study. Their parents were encouraged to participate. After written informed consent and clinic data had been obtained, genomic DNA was extracted from venous blood of participants. The target fragments were amplified by polymerase chain reaction (PCR) and subjected to bidirectional sequencing to identify sequence variations. Results: A total of 14 patients with prelingual NSHL and 6 normal parents were recruited. Genotyping revealed that one mutation, c.508_511dup (not 504insAACG), was homozygous in 1 patient, heterozygous in 2 patients and 3 parents, and compound heterozygous in 11 patients. Twelve patients had hearing loss caused by c.508_511dup in a homozygous or compound heterozygous form, and further study showed that it was wrongly named as 504insAACG. Additionally, according to the standard nomenclature, the previously reported mutations with distinct names from the literature review may be replaced by c.508_511dup. [ABSTRACT FROM AUTHOR]

Conclusions: In the study population in northwest China, a total of 33.06% of deaf patients have inherited hearing impairment caused by GJB2, SLC26A4, and mtDNA 1555A>G mutations. The mutation frequencies of GJB2, SLC26A4, and mtDNA 1555A>G genes were 16.12%, 10.54%, and 6.4%, respectively, in our study cohort. Thus, screening is conventionally performed for GJB2, SLC26A4, and mtDNA 1555A>G in these populations. Objective: This study aimed to investigate the mutations of GJB2, mitochondrial DNA 12S rRNA1555A>G, and SLC26A4 genes in Han Chinese, Hui people, and Tibetan ethnicities in patients with nonsyndromic hearing loss (NSHL) in northwest China. Methods: A total of 484 unrelated subjects with hearing loss who attended special education schools in northwest China were enrolled in this study. Three prominent deafness-related genes, GJB2, SLC26A4, and mtDNA 1555A>G, were screened for mutations in our study cohort. Results: The mutation frequencies of GJB2, SLC26A4, and mtDNA 1555A>G genes were 16.12%, 10.54%, and 6.4%, respectively. The prevalence of GJB2 mutations was 17.52%, 15.35%, and 11.43% in Han Chinese, Hui people, and Tibetan participants, respectively. c.235delC was the most prevalent mutation, accounting for 65.71% of all GJB2 mutant alleles. The prevalence of SLC26A4 mutations was 12.39%, 8.84%, and 8.57% in Han Chinese, Hui people, and Tibetan participants, respectively. The c.919-2 A>G mutation was the most common form, accounting for 60.47% of all SLC26A4 mutant alleles. The prevalence of the homoplasmic mtDNA 1555A>G mutation was 8.97%, 3.72%, and 5.71% in Han Chinese, Hui people, and Tibetan participants, respectively, which represents a statistically significant difference between the Han Chinese and Hui people (χ2 = 5.118, p < 0.05). [ABSTRACT FROM AUTHOR]

Conclusions: The GJB2 gene mutation characteristic of Dongxiang was the interaction result of ethnic background and geographical environment, and Yugur exhibited the typical founder effect. The SLC26A4 gene mutation characteristic of Dongxiang was related to caucasian backgrounds and selection of purpose exons, i.e. ethnic background and the penetrance of ethnic specificity caused the low mtDNA1555A>G mutation frequency in Dongxiang. Objectives: To determine the prevalence of GJB2 and SLC26A4 genes and mtDNA1555A>G mutations and analyze the ethnic specificity in the non-syndromic sensorineural hearing loss (NSHL) of unique ethnic groups in Gansu Province. Methods: Peripheral blood samples were obtained from Dongxiang, Yugur, Bonan, and ethnic Han groups with moderately severe to profound NSHL in Gansu Province. Bidirectional sequencing (or enzyme digestion) was applied to identify the sequence variations. Results: The pathogenic allele frequency of the three gene mutations was different. The frequency of the GJB2 gene among the Dongxiang, Yugur, Bonan, and ethnic Han groups was 9.03%, 12.5%, 5.88%, and 12.17%, respectively. No difference was found between the ethnic groups. The frequencies of the SLC26A4 genes were 3.23%, 8.33%, 0%, and 9.81%, respectively. The mutation frequency of mtDNA1555A>G was 0%, 0%, 0%, and 6.03%, respectively. No difference was found between the ethnic groups, except for the Dongxiang and ethnic Han groups, both in SLC26A4 gene and mtDNA1555A>G. [ABSTRACT FROM AUTHOR]

Abstract: It is known that enlarged vestibular aqueduct syndrome is closely related to the SLC26A4 mutation. Up to date, more than 200 of SLC26A4 mutations have been described, and novel mutations are being continually identified in different countries and ethnic groups. In this study, two novel variations were identified in a Chinese family associated with enlarged vestibular aqueduct. The two novel substitutions, c.232T>C and c.2006A>T, were detected in exon 3 and exon 17 of the pendrin encoding gene, respectively. The T/C transversion at 232 nucleotide caused p.Y78H mutation while the A/T transversion at 2006 nucleotide caused p.D669V mutation. [Copyright &y& Elsevier]

Abstract: To find new genes involved in fungal pathogenicity, a mutant (B11) exhibiting enhanced pathogenicity was isolated from an Agrobacterium-mediated transformed Magnaporthe oryzae mutant library. Southern blotting analysis showed that T-DNA insertion in the B11 genome was a single copy. TAIL-PCR and sequence alignment analyses revealed that a putative gene locus MG01679 was interrupted by the T-DNA fragment. By using the PCR-based method, the DNA and cDNA of the mutant gene MG01679 was cloned and sequenced. The open reading frame of MG01679 includes one intron and two exons, and the coding sequence is 696 bp in length and encodes a 231 amino acid peptide. Protein similarity analysis indicated that the gene belongs to the ThiJ/Pfp I protein family, and the gene was thus designated MgThiJ1. MgThiJ1 showed 57% similarity to FOXG_09029 from Fusarium oxysporum and 54% similarity to FGSG_08979 from F. graminearum in protein sequence. MgThiJ1 gene might act as a negative regulator in vegetative growth and pathogenesis in filamentous fungi, and its specific mechanism needs to be studied further. [Copyright &y& Elsevier]