Novel <i>MMP20</i> and <i>KLK4</i> Mutations in Amelogenesis Imperfecta

Seymen, F.,Park, J.-C.,Lee, K.-E.,Lee, H.-K.,Lee, D.-S.,Koruyucu, M.,Gencay, K.,Bayram, M.,Tuna, E.B.,Lee, Z.H.,Kim, Y.-J.,Kim, J.-W. SAGE Publications 2015 Journal of dental research Vol.94 No.8

<P>In order to achieve highly mineralized tooth enamel, enamel proteinases serve the important function of removing the remaining organic matrix in the mineralization and maturation of the enamel matrix. Mutations in the kallikrein 4 (<I>KLK4</I>), enamelysin (<I>MMP20</I>), and <I>WDR72</I> genes have been identified as causing hypomaturation enamel defects in an autosomal-recessive hereditary pattern. In this report, 2 consanguineous families with a hypomaturation-type enamel defect were recruited, and mutational analysis was performed to determine the molecular genetic etiology of the disease. Whole exome sequencing and autozygosity mapping identified novel homozygous mutations in the <I>KLK4</I> (c.620_621delCT, p.Ser207Trpfs*38) and <I>MMP20</I> (c.1054G>A, p.Glu352Lys) genes. Further analysis on the effect of the mutations on the translation, secretion, and function of KLK4 and MMP20 revealed that mutant KLK4 was degraded intracellularly and became inactive while mutant MMP20 was expressed at a normal level but secreted only minimally with proteolytic function.</P>

Exonal Deletion of <i>SLC24A4</i> Causes Hypomaturation Amelogenesis Imperfecta

Seymen, F.,Lee, K.-E.,Tran Le, C.G.,Yildirim, M.,Gencay, K.,Lee, Z.H.,Kim, J.-W. SAGE Publications 2014 Journal of dental research Vol.93 No.4

<P>Amelogenesis imperfecta is a heterogeneous group of genetic conditions affecting enamel formation. Recently, mutations in solute carrier family 24 member 4 (<I>SLC24A4</I>) have been identified to cause autosomal recessive hypomaturation amelogenesis imperfecta. We recruited a consanguineous family with hypomaturation amelogenesis imperfecta with generalized brown discoloration. Sequencing of the candidate genes identified a 10-kb deletion, including exons 15, 16, and most of the last exon of the <I>SLC24A4</I> gene. Interestingly, this deletion was caused by homologous recombination between two 354-bp-long homologous sequences located in intron 14 and the 3′ UTR. This is the first report of exonal deletion in <I>SLC24A4</I> providing confirmatory evidence that the function of SLC24A4 in calcium transport has a crucial role in the maturation stage of amelogenesis.</P>

Novel <i>ITGB6</i> mutation in autosomal recessive amelogenesis imperfecta

Seymen, F,Lee, K-E,Koruyucu, M,Gencay, K,Bayram, M,Tuna, EB,Lee, ZH,Kim, J-W Stockton Press 2015 Oral diseases Vol.21 No.4

<P><B>Objective</B></P><P>Hereditary defects in tooth enamel formation, amelogenesis imperfecta (AI), can be non-syndromic or syndromic phenotype. Integrins are signaling proteins that mediate cell–cell and cell–extracellular matrix communication, and their involvement in tooth development is well known. The purposes of this study were to identify genetic cause of an AI family and molecular pathogenesis underlying defective enamel formation.</P><P><B>Materials and Methods</B></P><P>We recruited a Turkish family with isolated AI and performed mutational analyses to clarify the underlying molecular genetic etiology.</P><P><B>Results</B></P><P>Autozygosity mapping and exome sequencing identified a novel homozygous <I>ITGB6</I> transversion mutation in exon 4 (c.517G>C, p.Gly173Arg). The glycine at this position in the middle of the <I>β</I>I-domain is conserved among a wide range of vertebrate orthologs and human paralogs. Clinically, the enamel was generally thin and pitted with pigmentation. Thicker enamel was noted at the cervical area of the molars.</P><P><B>Conclusions</B></P><P>In this study, we identified a novel homozygous <I>ITGB6</I> mutation causing isolated AI, and this advances the understanding of normal and pathologic enamel development.</P>

<i>ENAM</i> Mutations with Incomplete Penetrance

Seymen, F.,Lee, K.-E.,Koruyucu, M.,Gencay, K.,Bayram, M.,Tuna, E.B.,Lee, Z.H.,Kim, J.-W. Journal of Dental Research, Inc 2014 Journal of dental research Vol.93 No.10

<P>Amelogenesis imperfecta (AI) is a genetic disease affecting tooth enamel formation. AI can be an isolated entity or a phenotype of syndromes. To date, more than 10 genes have been associated with various forms of AI. We have identified 2 unrelated Turkish families with hypoplastic AI and performed mutational analysis. Whole-exome sequencing identified 2 novel heterozygous nonsense mutations in the <I>ENAM</I> gene (c.454G>T p.Glu152* in family 1, c.358C>T p.Gln120* in family 2) in the probands. Affected individuals were heterozygous for the mutation in each family. Segregation analysis within each family revealed individuals with incomplete penetrance or extremely mild enamel phenotype, in spite of having the same mutation with the other affected individuals. We believe that these findings will broaden our understanding of the clinical phenotype of AI caused by <I>ENAM</I> mutations.</P>

Novel FGF10 mutation in autosomal dominant aplasia of lacrimal and salivary glands

Seymen, F.,Koruyucu, M.,Toptanci, I. R.,Balsak, S.,Dedeoglu, S.,Celepkolu, T.,Shin, T. J.,Hyun, H. K.,Kim, Y. J.,Kim, J. W. Springer Science + Business Media 2017 Clinical oral investigations Vol.21 No.1

<P>Identification of the genetic etiology of the ALSG will help both the family members and dentist understand the nature of the disorder. Therefore, it will positively motivate oral health care to avoid further destruction of the tooth due to the lack of salivary production.</P>

Aneurysmal Bone Cysts of the Spine : Two Case Reports

Seymen Ozdemir,Can Yaldiz,Ferhat Ozden,Ozlem Kitiki Kacira,Tibet Kacira 대한척추신경외과학회 2014 Neurospine Vol.11 No.4

Aneurysmal bone cysts are rare entities which causes expansile and destructive bone lesions characterized by reactive proliferation of connective tissue. They usually grow rapidly with hypervascularity. In clinical practice they can be easily misdiagnosed due to the rare occurance and having no such typical findings as radiologically. Most cases have uncommon pain symptoms, but rarely, if fractures occur, neurological findings can be seen and the surgical treatment, if needed, could be difficult. We will discuss our evaluations to two cases that we experienced in our clinic in this report.

Effect of wild watermelon rootstocks and water stress on chemical properties of watermelon fruit

Musa Seymen,Duran Yavuz,Muhammet Ercan,Mehmet Akbulut,Hacer Çoklar,Ertan Sait Kurtar,Nurcan Yavuz,Sinan Süheri,Önder Türkmen 한국원예학회 2021 Horticulture, Environment, and Biotechnology Vol.62 No.3

Drought is one of the most important abiotic factors that restrict the production of agricultural plants. An eff ective way toavoid the negative eff ects of drought on crops is to cultivate high-yielding varieties by grafting them onto drought-tolerantrootstocks with a strong root system. For this purpose, fi ve diff erent plant materials were used: wild watermelon rootstock,i.e., wild watermelon (A 1 and A 2 ), open-pollinated Lagenaria siceraria (gourd) rootstocks (A3), Cucurbita maxima Duchesne× Cucurbita moschata Duchesne (TZ-148) F1 watermelon rootstocks (A 4 ), and the ungrafted control. Five diff erentirrigation depths were applied considering irrigation water (IW)/cumulative pan evaporation (CPE) rations (I 100 : 1.0 IW/CPE, I 75 :0.75 IW/CPE, I 50 :0.50 IW/CPE, I 35 :0.35 IW/CPE, and I 0 :rain-fed). The results showed that the use of rootstockand water stress increased the rate of sugar content in the fruit. The highest positive relationship was found between glucoseand total sugar, whereas the highest negative relationship was observed between sucrose and malic acid. Parameters such asglucose, total sugar, and citric acid showed signifi cant changes in drought stress. Fructose and malic acid showed signifi cantdiff erences between the rootstocks. Principal Component Analysis (PCA) revealed that the A 2 I 50 application was locatedin the positive region of both components and showed important results in these parameters. The TZ148 rootstock contributedsignifi cantly to the quality of watermelon. In addition, the A 2 wild watermelon rootstock showed respectable results,especially under water stress conditions. Based on these results, we conclude that the use of wild watermelon rootstock willcontribute to the fruit quality in arid and semi-arid areas with limited water resources.

Iron Supplementation in Experimental Hyperthyroidism: Effects on Oxidative Stress in Skeletal Muscle Tissue

Hakki Oktay Seymen,Sabiha Civelek,Arzu Seven,Gunnur Yigit,Husrev Hatemi,Gulden Burcak 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.SUP

This study was designed to investigate the effects of iron supplementation on the parameters of oxidative stress in the skeletal muscle tissue of hyperthyroidism induced rats. Hyperthyroidism was found to cause an increase in thiobarbituric acid-reactive substances (TBARS) and copper zinc superoxide dismutase (Cu, Zn SOD) activity, but decreases in the glutathione-peroxidase (GSH Px) activity and glutathione (GSH). Iron supplementation caused an increase in TBARS and a decrease in GSH. Iron supplementation in hyperthyroid rats attenuated the hyperthyroid state, but lowered the plasma ferritin level, which is considered an indicator of thyroid hormone action. Iron supplementation caused no additional increase in the TBARS in hyperthyroid rats, ameliorated the decrease in GSH content and abolished the induction of Cu, Zn SOD. Our findings suggested no increase, but a decrease, in the risk of oxidative stress in iron supplemented hyperthyroid rats. Whether supplementation of iron would have similar effects in humans should be further investigated in clinical studies.

Candidate Gene Strategy Reveals ENAM Mutations

Kang, H.-Y.,Seymen, F.,Lee, S.-K.,Yildirim, M.,Bahar Tuna, E.,Patir, A.,Lee, K.-E.,Kim, J.-W. SAGE Publications 2009 Journal of dental research Vol.88 No.3

<P>Amelogenesis imperfecta (AI) is a genetically and phenotypically heterogeneous genetic disorder affecting tooth enamel without other non-oral syndromic conditions. Based on a review of the literature, the authors constructed a candidate-gene-based mutational analysis strategy. To test the strategy, they identified two Turkish families with hypoplastic enamel without any other non-oral syndromic phenotype. The authors analyzed all exons and exon/intron boundaries of the enamelin (<I>ENAM</I>) gene for family 1 and the <I>DLX3</I> and <I> ENAM</I> genes for family 2, to identify the underlying genetic etiology. The analysis revealed 2 <I>ENAM</I> mutations (autosomal-dominant g.14917delT and autosomal-recessive g.13185-13186insAG mutations). A single T deletion in exon 10 is a novel deletional mutation (g.14917delT, c.2991delT), which is predicted to result in a frameshift with a premature termination codon (p.L998fsX1062). This result supports the use of a candidate-gene-based strategy to study the genetic basis for AI.</P>

<i>LAMB3</i> Mutations Causing Autosomal-dominant Amelogenesis Imperfecta

Kim, J.W.,Seymen, F.,Lee, K.E.,Ko, J.,Yildirim, M.,Tuna, E.B.,Gencay, K.,Shin, T.J.,Kyun, H.K.,Simmer, J.P.,Hu, J.C.-C. SAGE Publications 2013 Journal of dental research Vol.92 No.10

<P>Amelogenesis imperfecta (AI) can be either isolated or part of a larger syndrome. Junctional epidermolysis bullosa (JEB) is a collection of autosomal-recessive disorders featuring AI associated with skin fragility and other symptoms. JEB is a recessive syndrome usually caused by mutations in both alleles of <I>COL17A1, LAMA3, LAMB3</I>, or <I>LAMC2</I>. In rare cases, heterozygous carriers in JEB kindreds display enamel malformations in the absence of skin fragility (isolated AI). We recruited two kindreds with autosomal-dominant amelogenesis imperfecta (ADAI) characterized by generalized severe enamel hypoplasia with deep linear grooves and pits. Whole-exome sequencing of both probands identified novel heterozygous mutations in the last exon of <I>LAMB3</I> that likely truncated the protein. The mutations perfectly segregated with the enamel defects in both families. In Family 1, an 8-bp deletion (c.3446_3453del GACTGGAG) shifted the reading frame (p.Gly 1149Glufs*8). In Family 2, a single nucleotide substitution (c.C3431A) generated an in-frame translation termination codon (p.Ser1144*). We conclude that enamel formation is particularly sensitive to defects in hemidesmosome/basement-membrane complexes and that syndromic and non-syndromic forms of AI can be etiologically related.</P>