Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder in terms of cytogenetic and molecular aberrations. Ten-Eleven-Translocation 2 (TET2), Kirsten rat sarcoma viral oncogene homolog (KRAS), and Casitas B-cell lymphoma (CBL) have an important role pathogenesis of acute myeloid leukemia (AML) and their activated mutations confer proliferative and survival signals. Aim: In this study, we aimed to find possible genetic markers for molecular analysis in childhood AML by screening hot-spot exons of TET2, KRAS, and CBL using Next Generation Sequencing (NGS) analysis. In addition, association between found variants and mutations of Januse Kinase-2 (JAK2) and Fms-Related Tyrosine Kinase (FLT3) were analyzed which are important prognostic risk factors for AML. Methods: Eight patients who were diagnosed with pediatric AML at Losante Pediatric Hematology–Oncology Hospital were included to the study. Hot-spot exons of TET2, KRAS and CBL genes were screened using the NGS method. Furthermore, FLT3-Internal Tandem Duplicate (FLT3-ITD) and JAK2-V617F were analyzed by Real Time Polymerase chain Reaction (Real Time-PCR). Results: In total, we identified 20 variants in studied genes by NGS. In our patient group, 16 variants in the TET2 (seven novel, seven missense and two silent), two variants in the KRAS (one missense and one intronic) and two variants in the CBL (two novel) were found. All of AML patients were found negative for JAK V617 F. Three of the eight patients (37.5%) showed mutations of both FLT3-ITD and TET2, KRAS, CBL. Conclusion: We found novel mutations for TET2, KRAS, and CBL. The detected variants in this article seem to be the first screening results of genes studied by NGS in childhood AML patients. Our results also showed some degree of association between FLT3-ITD and TET2, KRAS, CBL mutations.

Objective: Myeloproliferative neoplasms (MPNs) like essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are acquired clonal hematopoietic stem cell disorders and originate from a multipotent hematopoietic stem cell. The SOCS1 and SOCS3 genes are negative regulators of the JAK/STAT signal pathway. In this study we investigate the promoter methylation of these genes in the pathogenesis of MPNs and secondary erythrocytosis/thrombocythemia. Materials and Methods: Promoter methylation of SOCS1 and SOCS3 genes was analyzed with methylation-specific PCR. PCR products were analyzed by agarose gel electrophoresis. Results: No disease-specific CpG island methylation of SOCS1 was observed. Hypermethylation of the SOCS3 promoter was identified in 5 out of 19 (26.3%) PV cases, 2 out of 21 (9.5%) ET cases, 1 out of 5 (20%) PMF cases, and 9 out of 42 (21.4%) cases of secondary erythrocytosis/thrombocythemia. Conclusion: The results revealed that promoter methylation of the SOCS3 gene suggests a possible role for SOCS3 methylation in the pathogenesis of MPNs and secondary erythrocytosis/thrombocythemia. Conflict of interest:None declared.

Gorlin-Chaudhry-Moss syndrome (OMIM 233500) is a rare congenital malformation syndrome with the cardinal manifestations of craniofacial dysostosis, hypertrichosis, underdeveloped genitalia, ocular, and dental anomalies. Since 1960, only six affected individuals have been reported. We report a 4-year and 6-month-old female patient with this phenotype and review the clinical presentation of all patients known so far. Previously unreported malformations of the extremities, larynx, and nose are also described, expanding the phenotype of this rare syndrome. Array-CGH analysis did not show pathological deletions or duplications.

BACKGROUND/AIMS:Chronic arthritis of familial Mediterranean fever (FMF) involves weight-bearing joints and can occur in patients without a history of acute attack. Our aim was to investigate a possible causal relationship between FMF and osteoarthritis in a population in which FMF is quite common.METHODS:Patients with late stage primary osteoarthritis were enrolled, and five MEFV gene mutations were investigated. The frequency of MEFV gene mutations was compared among patients with osteoarthritis and a previous healthy group from our center.RESULTS:One hundred patients with primary osteoarthritis and 100 healthy controls were studied. The frequency of MEFV gene mutations was significantly lower in the osteoarthritis group (9% vs. 19%). M694V was the most frequent mutation (5%) in the osteoarthritis group, whereas in the control group, E148Q was the most common (16%). In subgroup analyses, the mutation frequency of patients with hip osteoarthritis was not different from that of patients with knee osteoarthritis and controls (7.1%, 9.7%, and 19%, respectively). There were no differences among the three groups with respect to MEFV gene mutations other than E148Q (8.1% vs. 3.6%). E148Q was significantly lower in the osteoarthritis group than in the controls (16% vs. 1%), although the mutations did not differ between patients with knee osteoarthritis and controls.CONCLUSIONS:In a population with a high prevalence of MEFV gene mutations, we did not find an increased mutation rate in patients with primary osteoarthritis. Furthermore, we found that some mutations were significantly less frequent in patients with osteoarthritis. Although the number of patients studied was insufficient to claim that E148Q gene mutation protects against osteoarthritis, the potential of this gene merits further investigation.

Objective: Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder that leads to underproduction of normal blood cells. It causes dysgenesis of the blood cells. The cause of de novo MDS is not known. About 10% of cases of MDS are secondary, most often due to radiation treatment or chemotherapy for cancer. The role of other diseases observed in the patients and their families is not clear in the progression of MDS. Here, the diseases observed in our series (71 MDS cases and their families) were compared with the normal controls (71 normal cases and their families) to understand the affect of other diseases in the progression of MDS. Material and Methods: Among 71 MDS cases, 29 cases with refractory cytopenia with unilineage dysplasia, one cases with refractory anemia with ring sideroblast, 28 cases with refractory cytopenias with multilineage dysplasia, 11 cases with refractory anemia with excess blasts and 2 cases with MDS associated with isolated del (5q) were diagnosed with clinical and laboratory results. The diseases in MDS and the control groups were classified according to general classifications. Results: The numbers of affected patients in each group represented no significant difference between MDS and the control groups. According to these results, no correlation was found between the other diseases and MDS group. As known, some diseases have an accumulation in some families representing genetic predisposition. In order to find out the role of such systemic diseases frequently observed in one family, two groups were compared. In this group, the families which had two or more affected cases with the same diagnoses were accounted. Twenty six families had similar two or more diseases in MDS group whereas 21 families had similar two or more diseases in the control group. The difference between the MDS group (8 families) and the control group (2 families) which had rheumatic and autoimmune diseases were noticed. The number of affected families in MDS group with rheumatic and autoimmune diseases was greater than the number of affected families in the control group (p = 0.049). Conclusion: Our results may represent the possible role of rheumatic and autoimmune diseases in MDS etiology. Further findings are needed which represent the predisposition of rheumatic and autoimmune conditions in MDS progression.

Ozet Loseminin bir turu olan akut myeloblastik losemi (AML) myeloid seriye ait olgunlasmamis hucrelerin kemik iliginde, kanda, bazen diger dokularda asiri birikimi ile karakterize hematolojik kanserdir. Losemik hucre farklanmasinda kemik iligi ve periferik kan hucrelerinde klonal kromozomal anomaliler ortaya cikmaktadir. Bu anomaliler olgu tanisi ve prognozunu gostermesi acisindan onemlidir. Yazimizda prostat kanseri nedeni ile 12 yil once cerrahi ve hormon tedavisi alan ilk tani evresinde kompleks karyotip anomaliler tesbit edilen bir AML olgusu sunulmaktadir. Tanimlanan kompleks karyotipik anomalilerin prognoz uzerindeki etkisi tartisilmaktadir. Periferik kan ve kemik iligi incelemesinde AML tanisi konan 70 yasindaki erkek olgunun kemik iliginden yapilan sitogenetik incelemede 49, XY, -1, -2, +4, +6, +8, +8, -12, -13, der (1), +2 mar [3], 50, XY, -2, +4, +6, +8, +8, -13, +2mar [2], 50, XY, -2, +4, +6, +8, +11?, -13, +2 mar [1] saptandi. Kompleks karyotipler genelde olgularda kotu prognoz belirtecidir. AML tanisi konulan olgu her turlu destek tedavisine ragmen tanidan iki gun sonra kaybedildi. Sonuc olarak, ozellikle yasli AML’li hastalarda gerek tani, gerekse prognozun belirlenebilmesi icin genetik incelemelerin mutlaka yapilmasi gerekliligi goz onunde bulundurulmalidir. Anahtar sozcukler: Akut myeloid losemi, karyotipleme, kromozom anormallikleri, sitogenetik Abstract Acute myeloid leukemia (AML) is a type of leukemia which is characterized by the excessive accumulation of immature myeloid bone marrow precursor cells in the marrow itself, in peripheral blood and sometimes also in other tissues. During differentiation of leukemia cells, clonal chromosomal abnormalities emerge in bone marrow and in peripheral blood cells. These anomalies are important for the disease diagnosis and prognosis. Here, an AML case who underwent surgery for prostate cancer 12 years ago and received hormonal therapy is presented. Complex karyotypic abnormalities were present in the initial diagnosis phase The correlation between complex karyotypes and the prognosis in this case was discussed. Our 70 year-old patient was diagnosed as AML after peripheral blood and bone marrow analyses. His bone marrow cytogenetic analyses revealed 49, XY, -1, -2, +4, +6, +8, +8, -12, -13, der (1), +2 mar [3], 50, XY, -2, +4, +6, +8, +8, -13, +2mar [2], 50, XY, -2, +4, +6, +8, +11?, -13, +2 mar [1]. Complex karyotypes generally represents poor prognosis in AML cases. The patient died in two days after the initial diagnosis, although AML treatment was applied. As a result genetic examination should always be performed in elderly AML patients for both diagnosis and prediction of prognosis. Keywords: Acute myeloid leukemia, karyotyping, chromosome aberrations, cytogenetics

Ozet Prader Willi Sendromu (PWS), paternal 15. kromozomun uzun kolunun proksimal bolgesinin (15q11-13) delesyonu, bu bolgenin maternal uniparental dizomisi yada yeniden duzenlenmesi ile meydana gelir. Genellikle neonatal donemde hipotoni, beslenme guclugu, karakteristik kraniofasial gorunum ve hipogonadotropik hipogonadizm ile karakterizedir. Cocukluk doneminde ise gelisme geriligi, mental retardasyon ve obezite dikkat cekmektedir. Yazimizda, dismorfik yuz gorunumu, neonatal hipotonisite ve beslenme problemi olan 9 aylik bir erkek olgu sunulmaktadir. Klinik bulgulari PWS ile uyumlu olgumuzda karyotip ve Floresan insitu hibridizasyon (FISH) (15q11-13 bolgesi icin spesifik) analizi yapilmistir. Karyotip analizi normal bulunan olguda, FISH analizinde 15q11-13 gen bolgesinde delesyon saptanmistir. Aile, PWS'nin ileri yaslarda gorulebilecek patolojileri (gelisme geriligi, zeka geriligi, obezite, hipogonadizm) yonunden uyarilmis ve genetik danisma almistir. Dismorfik yuz gorunumu ile birlikte neonatal hipotonisitesi ve beslenme problemi bulunan olgularda, PWS tanisinin mutlaka dusunulmesi gerektigi ve tani icin FISH analizinin onemi olgumuzla bir daha ortaya konmustur. Anahtar sozcukler : Prader Willi Sendromu, erken tani, FISH Abstract Prader Willi syndrome (PWS) is due to a paternal deletion of the long arm of chromosome 15 (15q11-13), maternal uniparental dysomy or chromosomal rearrangement of this region. It is usually characterized by central hypotonia and feeding problems during the neonatal period, characteristic craniofacial appearance and hypogonadotrophic hypogonadism. Developmental delay, mental retardation and obesity can be observed during the childhood years. In our manuscript, we present a 9 month-old male with dysmorphic facial appearance, neonatal hypotonia and feeding difficulties. Since the phenotype was suggestive of PWS, we performed Fluorescence in situ Hybridization (FISH) analysis (specific for 15q11-13 region) along with routine karyotype. The case whose routine karyotype was found as normal, had a deletion in 15q11-13 region in FISH analysis. During genetic counseling, the family was informed about the future aspects (developmental delay, mental retardation, obesity, hypogonadism) of PWS. Our case represents the importance of diagnosis of PWS in early diagnosis with dysmorphic facial appearance, neonatal hypotonia and feeding difficulty findings and emphasizes the possible role of the FISH analysis for diagnosis. Keywords: Prader Willi Syndrome, early diagnosis, FISH

The oto-spondylo-mega-epiphyseal-dysplasia (OSMED) phenotype is an autosomal recessive trait that is a skeletal dysplasia with the hallmark findings of limb shortening, multiple skeletal and radiological abnormalities, mid-face hypoplasia with a flat nasal bridge, small upturned nasal tip, and sensorineural hearing loss. A 3.5-year-old girl born to consanguineous Turkish parents had characteristic facial features at birth: mid-face hypoplasia, mild hypertelorism, upslanting palpebral fissures, prominent supraorbital ridges, depressed nasal bridge, small upturned nasal tip, long philtrum, and micrognathia. Radiological examination at three years of age revealed large flaring metaphyses and wide flat epiphyses. The humerus and femur showed the characteristic dumbbell shape. She had bilateral hearing loss with no ophthalmologic findings. There is continuing debate over the clinical overlap and differential diagnosis of OSMED syndrome. The patient was examined considering Weissenbacher-Zweymuller, Stickler type 3, Marshall syndrome, and Kniest dysplasia as possible differential diagnoses. We believe that the presented patient clinically manifested features of OSMED syndrome. We would like to point out that the management of OSMED calls for a coordinated multidisciplinary approach.

Tekrarlayan dusuklerde, yaklasik olarak %70 oraninda herhangi bir neden saptanamamaktadir. Gebeligin sorunsuz devami icin uteroplasental dolasim cok onemlidir ve gebelik sirasinda koagulasyon faktorlerinde meydana gelen degisikliklerin, plasental damarlarda tikanikliga yol acabilecegini, dolayisiyla dusuk olusumunda rol alabilecekleri dusunulmustur. Maternal koagulasyon faktorlerini etkileyen Faktor V Leiden G1691A, Protrombin G20210A ve MTHFR C677T mutasyonlari tromboza yatkinligi saptamada genetik test olarak kullanilmaktadir. Bu yuzden maternal trombofililer ve bunlarin testleri klinik acidan buyuk onem tasimaktadir. Literaturde de bu parametrelerle ilgili yapilmis bircok calisma dikkati cekmektedir. Bu olguda, ailesinde multipl dusuk oykusu olan bir ciftte karyotip analizi yapilmis ve yukarida belirtilen mutasyonlar incelenmistir. Kromozom analizleri normal saptanan ciftte, baba adayinin MTHFR C677T mutasyonunu heterozigot olarak, anne adayinin ise homozigot olarak tasidigi saptandi. Bu ailede olasi diger faktorler ekarte edildiginden, MTHFR C677T mutasyonun ailedeki dusukleri aciklayabilecegi dusunuldu ve benzer oyku ile basvuran bireylerde, belirtilen analizlerin yapilmasinin tekrarlayan dusuk etiyolojisini aydinlatmada yardimci olabilecegi gosterilmistir

Ozet Sotos sendromu; makrosefali, tipik yuz gorunumu ve gelisim geriligi ile karakterize bir asiri buyume sendromudur. Sendromdan sorumlu gen nukleer reseptor baglayici SET domain1 (NSD1) proteinini kodlar. Beyaz irkta hastalarin %80’inden fazlasinda mutasyonlari gosterilmistir. Olgularin cogu sporadik olup, otozomal dominant kalitim modeline uyan aileler bildirilmistir. Sotos sendromunun prevalansi 1:10,000 ile 1:50,000 arasindadir. El, ayak ve cenedeki asiri buyume, klinik bulgu olarak akromegali ile karistirilmaktadir. Burada, akromegali tanisiyla takipli olup mental retardasyon etiyolojisinin arastirilmasi icin poliklinigimize yonlendirilen 15,5 yasinda bir erkek olgu sunulmaktadir. Olgunun kromozom analizinde 46, XY, t(3;6)(p21;p25) karyotipinde oldugu ve olguya ait aile taramasinda ise transloke kromozomun paternal orijinli oldugu saptanmistir. Sonuc olarak akromegali benzeri bulgular gosteren zeka geriligi bulunan olgularda ayirici tanida Sotos sendromu mutlaka dusunulmelidir. Anahtar sozcukler: Sotos sendromu, akromegali, zeka geriligi, translokasyon tasiyiciligi, makrosefali Abstract Sotos syndrome is an overgrowth syndrome characterized by macrocephaly, facial gestalt and developmental delay. The associated gene encodes nuclear receptor binding SET domain protein 1 (NSD1), whose mutations account for > %80 of white patients. Majority of the cases are sporadic, though autosomal dominant pedigrees have been published. The prevalance of Sotos’s syndrome is estimated at 1:10,000 to 1:50,000. Overgrowth of the hands, feet and chin overlap with the clinical features of acromegaly. Here, we present a 15.5 year old boy who was being followed as acromegaly and sent to our clinics for determining the etiology of mental retardation. In chromosomal analyses, t(3;6)(p21;p25) was observed, the fully karyotype was diagnosed as 46, XY, t(3;6)(p21;p25). In his detailed familial chromosomal analyses, the same translocation was found in his father karyotype. As a result, Sotos syndrome should be in the differential diagnosis list of any patient who has acromegalic features accompanying mental retardation. Key words: Sotos syndrome, acromegaly, mental retardation, translocation carrier, macrocephaly

Otodental syndrome has been described as a syndrome of sensorineural hearing loss and dental anomalies. In this syndrome, generally autosomal dominant inheritance pattern has been described. In this study, we present an 8-year-old girl with bilateral sensorineural hearing loss and partial anodonty findings in a non-consanguineous family without eye involvement. In literature, this syndrome has been reported only in few cases with high penetrance and variabile expressivity. Therefore, we assume that this case may be accepted as a variant form of otodental syndrome with solely neurosensorial hearing loss, anodonty and deep narrow palate findings without dental dysplasia and eye involvement.

American Journal of Medical Genetics Part AVolume 152A, Issue 11 p. 2886-2887 Research Letter The progeny of homozygous identical reciprocal translocation carrier mother† Altug Koç, Altug Koç Department of Medical Genetics, Gulhane Military Medical Academy, Ankara, TurkeySearch for more papers by this authorSefik Guran, Corresponding Author Sefik Guran sefguran@yahoo.com Department of Medical Biology, Gulhane Military Medical Academy, Ankara, TurkeyDepartment of Medical Biology, Gulhane Military Medical Academy, 06018 Etlik, Ankara, Turkey.Search for more papers by this authorMuhterem Bahce, Muhterem Bahce Department of Medical Genetics, Gulhane Military Medical Academy, Ankara, TurkeySearch for more papers by this author Altug Koç, Altug Koç Department of Medical Genetics, Gulhane Military Medical Academy, Ankara, TurkeySearch for more papers by this authorSefik Guran, Corresponding Author Sefik Guran sefguran@yahoo.com Department of Medical Biology, Gulhane Military Medical Academy, Ankara, TurkeyDepartment of Medical Biology, Gulhane Military Medical Academy, 06018 Etlik, Ankara, Turkey.Search for more papers by this authorMuhterem Bahce, Muhterem Bahce Department of Medical Genetics, Gulhane Military Medical Academy, Ankara, TurkeySearch for more papers by this author First published: 14 October 2010 https://doi.org/10.1002/ajmg.a.33144 † How to Cite this Article: Koç A, Guran S, Bahce M. 2009. The progeny of homozygous identical reciprocal translocation carrier mother. Am J Med Genet Part A 152A:2886–2887. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume152A, Issue11November 2010Pages 2886-2887 RelatedInformation

In this paper, a 7 month old male case born to a first degree cousin marriage, referred to our department for oculomotor apraxia and hypotonia, diagnosed as having Joubert syndrome is discussed. Broad forehead, depressed nasal bridge, hypertelorism, hypotonia and oculomotor apraxia were found in physical examination. Pulmoner stenosis was reported in echocardiography. His peripheral blood cytogenetic analysis revealed 46, XY normal constitutional karyotype. “Molar tooth sign”, a pathognomonic finding for this syndrome was observed in cranial magnetic resonance images. In Joubert syndrome; dysmorphic skeletal findings, liver and kidney problems can be observed. In early diagnosed cases, like our case, clinical follow up is important for detetion of the liver and kidney involvement. Key words: Joubert syndrome, oculomotor apraxia, molar sign, hypotonia, hypertelorism. Ozet Makalede 1. derece kuzen evliligi bulunan ailenin okulomotor apraksi sikayeti olan ve Joubert sendromu tanisi almis 7 aylik erkek cocugu sunulmaktadir. Fizik muayenede genis alin yapisi, basik burun koku, hipertelorizm, hipotoni ve okulomotor apraksi saptanmistir. Ekokardiyografi (EKO) pulmoner stenoz varligini gostermistir. Olgunun periferik kan sitogenetik analizinde 46, XY normal karyotip yapilanmasi bulunmus olup, kranial MR sonucunda bu sendrom icin tani koydurucu olan “molar dis” gorunumu saptanmistir. Bu taniyi alan olgularda dismorfik iskelet yapisi, karaciger ve bobrek tutulumu bulgulari da olabilecegi goz onunde bulundurulmalidir. Olgumuz gibi erken tani konan hastalarda bobrek ve karaciger tutulumu yonunden klinik takip onemlidir. Anahtar sozcukler: Joubert sendromu, okulomotor apraksi, molar dis gorunumu, hipotoni, hipertelorizm.

We report on a patient with partial monosomy 6p and partial trisomy 12q identified by fluorescent in situ hybridization (FISH) and array-based comparative genomic hybridization (aCGH). She had a complex phenotype characterized by mental retardation (MR), psychomotor developmental delay, speech disorder, hypertelorism, eye anomalies, hearing loss, low-set malformed ears, thin upper lip, heart defect, clinodactyly, pes valgus, and skeletal anomalies. There is phenotypic overlap between our case and Mutchinick syndrome. This is the first report of a combined partial monosomy 6p and partial trisomy 12q due to an unbalanced translocation between subtelomeric regions of these chromosomes.

Acute non-lymphocytic leukemia is characterized by excessive accumulation of immature non lymphocytic bone marrow precursor cells in the marrow itself, and in peripheral blood. Here, a 23 year-old female patient with acute nonlymphocytic leukemia with inversion 16 and trisomy 22 cytogenetic findings is presented. As known, inversion 16 is generally related to acute myeloid leukemia M4 subtype. Trisomy 22 which represents poor prognosis is generally reported with inversion 16 in acute myeloid leukemia. Our case was treated with idarubicin and cytosine arabinoside at her initial diagnosis phase two years ago. In the relapse phase, trisomy 22 and inversion 16 was found sixteen months later. After the idarubicin and cytosine arabinoside treatment, blastic cell ratio was found to be 9.8% and myelosuppression occurred. This finding represents the necessity of detailed cytogenetic and molecular cytogenetic analyses in leukemia cases in initial diagnosis and treatment phases for predicting the prognosis.

Although the incidence of Hodgkin lymphoma (HL)--a lymphoid tissue malignity--increases in the presence of several viruses, particularly EBV, as well as with autoimmune diseases and following transplantation, although to date, the exact etiopathogenesis is not known. The higher frequency of HL among family members suggests involvement of genetic factors in its etiology. Studies aiming to elucidate the etiopathogenesis of patients with familial HL (FHL) have reported that human leukocyte antigen (HLA) haplotypes might be involved. In this case presentation, the associations between HLs diagnosed in a father of consanguineous marriage and his two children and HLAs in other family members were investigated and the findings are discussed in view of the published literature; no direct association was found between HLA alleles and the development of the disease in the present case with familial HL.