Unexpected identification of a recurrent mutation in the DLX3 gene causing amelogenesis imperfecta

Objective To identify the molecular genetic aetiology of a family with autosomal dominant amelogenesis imperfecta (AI). Subjects and Methods DNA samples were collected from a six-generation family, and the candidate gene approach was used to screen for the enamelin (ENAM) gene. Whole-exome sequencing and linkage analysis with SNP array data identified linked regions, and candidate gene screening was performed. Results Mutational analysis revealed a mutation (c.561_562delCT and p.Tyr188Glnfs*13) in the DLX3 gene. After finding a recurrent DLX3 mutation, the clinical phenotype of the family members was re-examined. The proband's mother had pulp elongation in the third molars. The proband had not hair phenotype, but her cousin had curly hair at birth. Conclusions In this study, we identified a recurrent 2-bp deletional DLX3 mutation in a new family. The clinical phenotype was the mildest one associated with the DLX3 mutations. These results will advance the understanding of the functional role of DLX3 in developmental processes.OAIID:RECH_ACHV_DSTSH_NO:T201604269RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A080446CITE_RATE:2FILENAME:Kim_et_al-2016-Oral_Diseases.pdfDEPT_NM:치의학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/1f942450-fa58-4bd3-8e50-692d90fed3c6/linkCONFIRM:

Prevalence and antibiotic resistance profiles of Enterococcus species in chicken at slaughter level; absence of vanA and vanB genes in E. faecalis and E. faecium

Gencay, Yilmaz Emre/0000-0002-2154-9663;WOS: 000282120400003PubMed: 20189617The prevalence of enterococci in neck skin samples of poultry from Ankara region in Turkey was investigated and their antibiotic resistance patterns were determined. In the study, 83 of 106 analyzed neck skin samples were positive for Enterococcus, with E. faecium as the most prevalent species (48%) followed by E. durans (23%) and E. faecalis (19%). Lower numbers were detected for E. gallinarum, E. hirae, E. mundtii and E. casseliflavus. Using the disc diffusion method, it was established that over 90% of E. faecium and E. faecalis isolates were high-level resistant against erythromycin and tetracycline. Four E. faecium isolates were additionally resistant to chloramphenicol, gentamicin and streptomycin, though they were susceptible to penicillin G. The most frequently observed multiple resistance in E. faecium (25%) was against erythromycin, tetracycline, chloramphenicol and streptomycin. Of the E. faecalis isolates, 44% were multiple resistant to erythromycin, tetracycline and streptomycin. Vancomycin resistance could not be demonstrated phenotypically and vanA or vanB genes were not detected by multiplex PCR in any of the isolates. Nevertheless, the observed resistance patterns are of concern for public health. (C) 2010 Elsevier Ltd. All rights reserved

Recessive Mutations in ACP4 Cause Amelogenesis Imperfecta

Amelogenesis imperfecta (AI) is an innate disorder that affects the formation and mineralization of the tooth enamel. When diagnosed with AI, one's teeth can be hypoplastic (thin enamel), hypomature (normal enamel thickness but discolored and softer than normal enamel), hypocalcified (normal enamel thickness but extremely weak), or mixed conditions of the above. Numerous studies have revealed the genes that are involved in causing AI. Recently, ACP4 (acid phosphatase 4) was newly found as a gene causing hypoplastic AI, and it was suggested that mutant forms of ACP4 might affect access to the catalytic core or the ability to form a homodimer. In this study, a Korean and a Turkish family with hypoplastic AI were recruited, and their exome sequences were analyzed. Biallelic mutations were revealed in ACP4: paternal (NM_033068: c.419C>T, p.(Pro140Leu)) and maternal (c.262C>A, p.(Arg88Ser)) mutations in family 1 and a paternal (c.713C>T, p.(Ser238Leu)) mutation and de novo (c.350A>G, p.(Gln117Arg)) mutation in the maternal allele in family 2. Mutations were analyzed by cloning, mutagenesis, immunofluorescence, immunoprecipitation, and acid phosphatase activity test. Comparison between the wild-type and mutant ACP4s showed a decreased amount of protein expression from the mutant forms, a decreased ability to form a homodimer, and a decreased acid phosphatase activity level. We believe that these findings will not only expand the mutational spectrum of ACP4 but also increase our understanding of the mechanism of ACP4 function during normal and pathologic amelogenesis

Biological predictors of mandibular asymmetries in children with mixed dentition

OBJECTIVES: The objective was to investigate the severity of skeletal mandibular asymmetry in children with mixed dentition and other factors associated with asymmetry. METHOD: The study was cross sectional, with stratified sampling according to malocclusion type consisting of 205 subjects with mixed dentition (median 10, interquartile range 9-11 years). There were 59 subjects presenting Class II/1, 77 Class II/2, and 69 Class III. The mandibular asymmetry has been estimated from orthopantomograms using the Habets' method and the dental maturation by Demirjian's method. The sagittal skeletal relationship and facial growth pattern were assessed from lateral cephalograms. RESULTS: Asymmetries in general, were not rare and were more present in the condylar height rather than in the height of the ramus. The highest severity of condylar asymmetry was in Class II/2 subjects (median of asymmetry index 7.3 ; 64% subjects exhibiting moderate and severe asymmetry), while the Class III subjects exhibited the highest severity of both ramus and total height asymmetry (2.1 ; 13% and 2.0 ; 15%, respectively). Multiple logistic regression unveiled male gender as the only predictor of moderate or significant overall asymmetry. Dental age, the difference between dental and chronological age, and facial growth pattern were not significant predictors of asymmetries. DISCUSSION: Overall, asymmetries in mixed dentition cannot be considered rare ; however, no strong relationships between asymmetry and observed biological factors were found

Hypoplastic AI with Highly Variable Expressivity Caused by ENAM Mutations

Tooth enamel, the hardest tissue in the human body, is formed after a complex series of interactions between dental epithelial tissue and the underlying ectomesenchyme. Nonsyndromic amelogenesis imperfecta (AI) is a rare genetic disorder affecting tooth enamel without other nonoral symptoms. In this study, we identified 2 novel ENAM mutations in 2 families with hypoplastic AI by whole exome sequencing. Family 1 had a heterozygous splicing donor site mutation in intron 4, NM_031889; c.123+2T>G. Affected individuals had hypoplastic enamel with or without the characteristic horizontal hypoplastic grooves in some teeth. Family 2 had a nonsense mutation in the last exon, c.1842C>G, p.(Tyr614*), that was predicted to truncate the protein by 500 amino acids. Participating individuals had at least 1 mutant allele, while the proband had a homozygous mutation. Most interestingly, the clinical phenotype of the individuals harboring the heterozygous mutation varied from a lack of penetrance to a mild hypoplastic enamel defect. We believe that these findings will broaden our understanding of the clinical phenotype of AI caused by ENAM mutations

DS_10.1177_0022034518763152 – Hypoplastic AI with Highly Variable Expressivity Caused by <i>ENAM</i> Mutations

<p>Supplemental material, DS_10.1177_0022034518763152 for Hypoplastic AI with Highly Variable Expressivity Caused by <i>ENAM</i> Mutations by M. Koruyucu, J. Kang, Y.J. Kim, F. Seymen, Y. Kasimoglu, Z.H. Lee, T.J. Shin, H.K. Hyun, Y.J. Kim, S.H. Lee, J.C.C. Hu, J.P. Simmer and J.W. Kim in Journal of Dental Research</p