Comparison of MicroRNA Levels of 18-60-month-old Autistic Children with Those of Their Siblings and Controls.

Objective: The present study aims to compare the levels of 7 microRNAs (mi-RNAs) (mi-RNA-125b, mi-RNA-23a-3p, mi-RNA-146a-5p, mi-RNA-106a, mi-RNA-151a-3p, mi-RNA-28, mi-RNA-125a) in the blood of the preschool children with autism and those of their siblings with healthy controls, and to investigate the association between these mi-RNAs and the severity of autism, behavioral problems, and siblings' autistic traits. Methods: A total of 35 children diagnosed with autism spectrum disorder (ASD) at the ages of 18-60 months (patient group), 35 non-affected siblings of the ASD group (sibling group), and 30 control subjects (control group) were involved in the study. The severity of ASD was measured using the Childhood Autism Rating Scale and the Autism Behavior Checklist (ABC). The behavioral problems of the children with ASD were assessed with the Aberrant Behavior Checklist, and the autistic traits of the siblings were assessed using the Autism spectrum screening scale for children. Results: mi-RNA-106a-5p, mi-RNA-151a-3p, and mi-RNA-28-3p were found to be expressed significantly lower in the patient group compared to the control group. There was a significant positive correlation between mi-RNA-23a and the sensory subscale of the ABC. mi-RNA-151a was significantly associated with sound sensitivity and mi-RNA-28 with echolalia. After controlling for age and sex, the differences between groups were disappeared. Conclusion: The present study examined mi-RNAs that have been reported as biomarkers in the literature. Although several symptom clusters are found to be related to certain mi-RNA expression levels, they were not found to be significant in discriminating the patient and healthy groups.

The XRCC1 and TP53 gene polymorphisms are associated with advanced-stage disease and early distant metastasis at diagnosis in non-small cell lung cancer.

Background: Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC. Objective: This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC. Material and Methods: In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis. Results: The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031). Conclusions: We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

Novel findings, mini-review and dysmorphological characterization of 16p13.11 microduplication syndrome.

The short arm of chromosome 16 and especially the region 16p13.11 is a chromosome region where many structural variants, especially deletions and duplications, can be observed. Although deletions of this region are clinically well defined, duplications are rare, and so far, there is no established clinical consensus in regard with its clinical picture, and especially the dysmorphic perspective of the disease is far from being clear. A 5-year-and-2-month-old patient who presented with epilepsy, autism and late speech onset complaints was evaluated in our genetics department. On physical examination, unilateral preauricular skin tag and upslanting palpebral fissures were noted. Microarray analysis was performed and reported as ([hg19]: 16p13.11 (14.897.804-16.730.375) x3). The literature review revealed only a few reports about the syndrome, but some dysmorphological findings appear to recur in different reports, which enables a possible characterization. Dysmorphic findings were discussed.

Localized Placental Mesenchymal Dysplasia in Monochorionic Diamniotic Twin Placenta with Beckwith-Wiedemann Syndrome.

IntroductionPlacental mesenchymal dysplasia (PMD) is often associated with Beckwith-Wiedemann syndrome. Case report: A 27-year-old woman with preeclampsia prematurely delivered twin girls. One side of the placenta was larger with numerous grape-like vesicles, histologically with large, cystic, stem villi with cisterns without syncytiotrophoblastic hyperplasia. This side showed mosaicism for chromosome 11 by FISH and hypomethylation at ICR2 by MLPA. The smaller side of the placenta was normal macroscopically, microscopically, and karyotypically. There was symmetric growth restriction, macroglossia and hypoglycemia of the girl corresponding to the abnormal placental side, and lesser symmetric growth restriction and mild hypoglycemia in the other girl. Conclusion: Localized placental mesenchymal dysplasia can occur in monochorionic diamniotic twin placenta with Beckwith-Wiedemann syndrome. Fetal affects may be asymmetric. PMD can be associated with mosaicism monosomy of chromosome 11.

Evaluation of immunological abnormalities in patients with rare syndromes.

Introduction: Recurrent infections are important problems in syndromic patients. This study aimed to evaluate immunological abnormalities in patients who presented with recurrent infections and were diagnosed with rare syndromes. Material and methods: This retrospective analysis included 14 patients with complaints of recurrent infections, all of whom were diagnosed with a rare syndrome. Results: The study group consisted of patients with Aicardi syndrome, Brugada syndrome, Phelan- McDermid syndrome, trichothiodystrophy, LEOPARD syndrome, Prader-Willi syndrome, Seckel syndrome, trisomy 18 (Edwards' syndrome), Wiedemann-Steiner syndrome, West syndrome, Williams syndrome, 47,XYY syndrome, 16p13 deletion syndrome, and 13q1.3 deletion syndrome. Seven patients (50%) were girls and seven (50%) were boys (mean age, 56.7 ±32.9 months; median [range] age: 45.5 [27-153] months). There were high rates of consanguinity (50%), cesarean section delivery (71%), and hospitalization in the intensive care unit (78.5%). No patients had a family history of immunodeficiency. On admission, all patients exhibited humoral and/or cellular immune system abnormalities. During the follow-up period, all T-cell abnormalities were improved after immunoglobulin replacement therapy (IGRT), while B-cell abnormalities persisted. These findings suggested that the patients predominantly had antibody deficiencies associated with mild T-cell abnormalities because of recurrent infections. The rates of infections and hospitalizations were significantly reduced after IGRT (p < 0.001); the rate of intensive care unit admission also significantly decreased (from 78.5% to 21.4%). Two of the three oxygen-dependent patients exhibited improvement therein. IGRT was discontinued in two patients with significant clinical improvement during follow-up. Conclusions: An immunological evaluation should be considered in pediatric patients with rare syndromes and recurrent infections. IGRT may help to improve the prognoses of these patients.

The Genetic Analysis of Cystic Fibrosis Patients With Seven Novel Mutations in the CFTR Gene in the Central Anatolian Region of Turkey.

BACKGROUND: Cystic fibrosis, a pulmonary disease which is an autosomal recessive, inherited, multisystemic genetic disease commonly seen in the Caucasian race, is the most frequent cause of mortality and morbidity. So far, more than 2000 disease-causing gene variants have been found and this number has been increasing with the studies conducted. Although there is not yet enough data that include the Turkish population, the recent increase of studies is noteworthy. AIMS: To discover the genetic variation in patients diagnosed with cystic fibrosis in the Central Anatolian region. STUDY DESIGN: Cross-sectional study. METHODS: The study was carried out in the Central Anatolian region in 3 pediatric pulmonology departments (Kayseri, Konya, and Ankara) in Turkey between July 2014 and December 2017. The Sanger and Next Generation Sequence analyses were used for exon and exon-intron boundaries in the cystic fibrosis transmembrane conductance regulatory (CFTR) gene, and in selected patients, mutation analysis was performed using the Multiplex Ligation-dependent Probe Amplification technique for large deletions and duplications. RESULTS: CFTR gene analysis was performed for 316 patients and 215 of them were genetically diagnosed with cystic fibrosis. Sixtythree different variants were defined in these patients and 7 of these were large deletions/duplications detected with the MLPA method. The most frequent variants were F508del (29.6%), G85E (8.2%), N1303K (8.2%), Y515* (7.5%), and G542* (3.4%). CONCLUSION: Using sequencing and Multiplex Ligation-dependent Probe Amplification methods, the identification of seven new mutations that were not previously reported in the literature contributes to a better understanding of the heterogeneous nature of CFTR mutations in the Turkish population. When no mutations are detected (pathogenic/probably pathogenic) in clinically compatible cases, Multiplex Ligationdependent Probe Amplification analysis contributes significantly to the diagnosis.

Interchromosomal effect: Report of a father and son, bearing different translocations of the same chromosome, and a review of the current literature.

Interchromosomal effect is a controversial phenomenon postulating that during gametogenesis of translocation carriers, aside from the unbalanced segregation of chromosomes involved in the translocation, other, structurally normal chromosomes might also be affected and segregated abnormally. Here, we present a balanced reciprocal translocation carrier t(15;20)(q11;p13), and his son, bearing a different translocation of chromosome 15, t(15;Y)(q11;q12). To further elucidate the so-far-controversial interchromosomal effect phenomenon, published original articles and case reports about interchromosomal effect were reviewed. The father was a carrier of t(15;20)(q11;p13). His wife's karyotype was normal. During a pregnancy occurred without any preceding procedure, amniocentesis was recommended to the family and performed. Result of the amniocentesis revealed a different translocation of chromosome 15; t(15;Y)(q11;q12). To our knowledge, this is the first report of two generations within a family, bearing different translocations of a chromosome. On top of all previous studies investigating ICE, our case adds an important finding, showing not only the rate of aneuploidies of structurally normal chromosomes, but also the rate of this 'alternating translocations' might be increased in translocation carriers, and this could be an important clue about interchromosomal effects.

A Novel Pathogenic Variant of the CFTR Gene in a Patient with Cystic Fibrosis Phenotype-c.4096A > T.

Cystic fibrosis is a chronic multisystemic disease originating from functional alterations in CFTR (cystic fibrosis transmembrane conductance regulator) protein. To date, more than 300 pathogenic variants have been described in the literature. However, the diagnosis of CF, which was thought to become easier after the CFTR gene was identified, became more complicated due to the enormous amount of variations. In this study, we present a patient whose clinical findings were consistent with cystic fibrosis (CF) and showed a homozygous missense change that is not previously reported in the CFTR gene as pathogenic. In the next-generation sequencing analysis, homozygous c.4096A > T single-nucleotide exchange (I1366F [p.Ile1366Phe], missense) was shown in both alleles of the patient' CFTR gene. According to our database analysis, this variant has not yet been previously reported (VarSome, ClinVar, MutationTaster, Ensembl, dbSNP, PubMed). We do consider the change as pathogenic since the patient's findings were compatible with CF and the data analysis was in favor of pathogenicity. The most recent consensus report published in 2017 emphasized the importance of CFTR gene analysis, and this study emphasizes the difficulties of associating CFTR gene variations with a clinical picture and constitutes a new data on the genotype-phenotype correlation of CFTR variants. Also, considering the frequency of CF (according to World Health Organization data, every 1 out of 2,000-3,000 infants is born with CF in European Union countries and every 1 out of 3,500 in the United States) as well as the increasing rate of molecular studies performed on CF patients worldwide, reporting novel variation has an additional value.

Investigation of the relationship between ischemic stroke and endothelial nitric oxide synthase gene polymorphisms [G894T, intron 4 VNTR and T786C]

Background/aim: We aimed to investigate the associations between endothelial nitric oxide synthase(eNOS) gene polymorphisms [G894T (rs1799983)], intron 4 (27-bpTR) variable number tandem repeat (VNTR) and T786C (rs2070744), and ischemic stroke in the Anatolian population. Materials and methods: This case-control study included 112 patients with "stroke of undetermined etiology" and 160 controls. Real-time polymerase chain reaction (RT-PCR) analysis was used to analyze these polymorphisms. Between-group frequencies of alleles and genotypes were compared using binary logistic regression analysis. Results: No significant difference was observed between the two groups in terms of the genotype and allele distributions of the eNOS G894T (rs1799983) polymorphism (P > 0.05). The a alleles and the 4b/a and 4a/a genotypes of the intron 4 (27-bpTR) VNTR polymorphism had significantly higher frequencies in the patient group than in the control group (OR: 2.715, P < 0.001; OR: 3.396, P < 0.001; OR: 10.631, P = 0.016, respectively). On the contrary, the TC genotype and C alleles of the T786C (rs2070744) polymorphism had a significantly lower frequency in the patient group than in the control group (OR: 0.244, P < 0.001, OR: 0.605, P = 0.006, respectively) Conclusion: Our findings indicate that the eNOS G894T and T786C [rs2070744] polymorphisms are not associated with the risk of ischemic stroke, whereas the intron 4 [27-bpTR] VNTR may be a risk factor in the Anatolian population.

A rare case in literature: Isochromosome Xq in Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome(KS), affecting 1 in 500-1,000 newborn males, is the most common sex chromosome aneuploidy among males with primary hypogonadism. Isochromosome Xq on the other hand is a rare variant of Klinefelter syndrome, accounting approximately 0.3% of all KS and associated with normal height and androgenisation compared to classical KS. Here, we present a case of isochromosome Xq variant of KS with similar clinical and cytogenetic findings with the few cases reported before. MATERIALS AND METHODS: A 25-year-old male patient referred to our clinic with complaint of infertility. He is the son of a consanguineous couple who are first cousins and there was no family history of reproductive difficulty. In physical examination synophrys, prominent ear and small testicles noted. The patient's spermiogram showed azoospermia and scrotal USG revealed testicular atrophy. RESULTS: Karyotype analysis using G-banding resulted as 47,X,i(X)(q10),Y, and STR analysis showed no deletion in AZF and SRY loci of interest. CONCLUSION: Although several isochromosome Xq variant of KS cases can be found in literature, it is our duty to emphasise the importance of karyotyping for patients with reproductive difficulty who may not have all features of classical Klinefelter syndrome.

Analysis of genetic polymorphisms associated with intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a common degenerative spinal condition. Recent studies have shown that the incidence of disc herniation and disc degeneration may be explained by genetic factors.  In this study, we investigated the link between various polymorphic variants of the vitamin D receptor (VDR), matrix metalloproteinase 2 (MMP2), and insulin like growth factor 1 receptor (IGF1R) genes and IVDD in patients with IVDD, in Turkey. We examined and genotyped 199 patients with IVDD and 197 healthy individuals. Genomic DNA was isolated from the peripheral blood leukocytes of all participants, and analyzed using real-time PCR. Via melting curve analysis, VDR, MMP2, and IGF1R polymorphism variant distributions were determined. The patients with IVDD showed higher frequencies of the VDR ApaI A allele genotype as compared to the control group; however, there were no significant differences in the frequencies or allelic distributions of the IGF1R and MMP2 genotypes between the IVDD patients and the control group. The incidence of IVDD in these Turkish patients is correlated with the VDR ApaI gene polymorphism, but not with the IGF1R and MMP2 polymorphisms.

NAT2 Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris.

Psoriasis is a common, chronic, and autoimmune skin disease. Factors that play a role in etiopathogenesis of psoriasis include internal factors such as genetic susceptibility and immunological factors and external factors such as stress, infection, trauma, drug, and environmental compounds. N-acetyltransferase 2 (NAT2) is a xenobiotic enzyme that is involved in the metabolism of drugs, environmental toxins, and carcinogens. In this study, we aimed to demonstrate whether the variations in the NAT2 gene lead to a predisposition to psoriasis by affecting the enzyme's ability to metabolize drugs and environmental components or not. Three polymorphisms (rs1799929, rs1799930, and rs1799931) in NAT2 gene were genotyped and compared by real-time PCR method in 260 psoriasis vulgaris patients and 200 healthy controls. There was no difference in the genotype distributions and allele frequencies of polymorphisms between psoriasis vulgaris patients and controls. When the effects of polymorphisms on the clinical features of the disease, such as onset age and severity, are assessed, it has been found that rs1799930 and rs1799929 are, respectively, associated with early onset age and severity of the disease. In conclusion, rs1799929, rs1799930, and rs1799931 polymorphisms of the NAT-2 gene do not appear to be a risk factor for the development of psoriasis. Conversely, they may have an effect on either more severe or early onset cases of the disease.

Male infertility associated with de novo pericentric inversion of chromosome 1.

Inversion occurs after two breaks in a chromosome have happened and the segment rotates 180° before reinserting. Inversion carriers have produced abnormal gametes if there is an odd number crossing- over between the inverted and the normal homologous chromosomes causing a duplication or deletion. Reproductive risks such as infertility, abortion, stillbirth and birth of malformed child would be expected in that case. A 54-year- old male patient was consulted to our clinic for primary infertility. The routine chromosome study were applied using peripheral blood lymphocyte cultures and analyzed by giemsa-trypsin-giemsa (GTG) banding, and centromer banding (C-banding) stains. Y chromosome microdeletions in the azoospermia factor (AZF) regions were analyzed with polymerase chain reaction. Additional test such as fluorescence in situ hybridization (FISH) was used to detect the sex-determining region of the Y chromosome (SRY). Semen analysis showed azoospermia. A large pericentric inversion of chromosome 1 46,XY, inv(1) (p22q32) was found in routine chromosome analysis. No microdeletions were seen in AZF regions. In our patient the presence of SRY region was observed by using FISH technique with SRY-specific probe. Men who have pericentric inversion of chromosome 1, appear to be at risk for infertility brought about by spermatogenic breakdown. The etiopathogenic relationship between azoospermia and pericentric inversion of chromosome 1 is discussed.

Would mean platelet volume/platelet count ratio be used as a novel formula to predict 22q11.2 deletion syndrome?

BACKGROUND: The diagnosis of 22q11.2 deletion syndrome depends on a time-consuming and expensive method, fluorescence in situ hybridisation (FISH). OBJECTIVES: We aimed to determine new parameters which can aid for in the diagnosis of 22q11.2 deletion syndrome. METHODS: Twenty two patients with 22q11.2 or 10p13 deletion were evaluated retrospectively. RESULTS: Facial-dysmorphism and mental-motor retardation were detected in 100% of patients. Mean platelet (PLT) counts were lower (224,980 versus 354,000, p = 0.001), mean PLT volume (MPV) (9.95 versus 7.07, p = 0.002), and MPV/PLTx105 ratios (5.36 versus 2.08, p < 0.001) were higher in patients with 22q11.2 deletion compared with the control group. Area under the receiver-operator characteristic (ROC) curve was 0.864, sensitivity was 84.6%, specificity was 90.9%, positive predictive value (PPV) was 91.7%, and negative predictive value (NPV) was 83.3% when MPV was 8.6. Area under ROC curve was 0.864, sensitivity was 76.9%, specificity was 90.1%, PPV was 90.1%, and NPV was 76.3% when PLT was 265,500. Area under ROC curve was 0.906, sensitivity was 84.6%, specificity was 100%, PPV was 100%, and NPV was 84.6% when MPV/PLTx105 was 3.3. Expression of PLT surface markers which were not in the GPIb-V-IX receptor complex (CD61, CD41a) increased as the surface area increased, but markers which were in a complex (CD42a, CD42b) did not change. CONCLUSIONS: High MPV/PLT value can be a good predictor for the diagnosis of 22q11.2 deletion syndrome. We suggest that in patients with facial dysmorphism and retardation in neurodevelopmental milestones and if MPV≥8.6fl, MPV/PLTx105 ratio≥3.3 and PLT count ≤265,500/mm3, the patients should be tested by FISH analysis to confirm the 22q11.2 deletion. If there are no macrothrombocytes, the 10p13 deletion should be tested in suspected cases.

Association of Apolipoprotein E Polymorphism with Intravitreal Ranibizumab Treatment Outcomes in Age-Related Macular Degeneration.

PURPOSE: Genetic factors are known to influence the response to anti-vascular endothelial growth factor (VEGF) treatment in exudative age-related macular degeneration (AMD). The current study was conducted to investigate the association of Apolipoprotein E (ApoE) polymorphism with the treatment response to ranibizumab for exudative AMD. METHODS: One hundred nine eyes (109 patients, 59.6% male, mean age 63.84 ± 7.22 years) treated with intravitreal ranibizumab injections were included in the analysis. Smoking status and lesion type were recorded. Patients were categorized into three groups according to visual acuity (VA) change at 6 months after the first injection: VA loss >5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Group 1); VA change between five ETDRS letters gain and loss (Group 2); VA improvement >5 ETDRS letters (Group 3). The association of ApoE gene polymorphisms with the three groups was evaluated. RESULTS: Both smoking status and lesion type showed no significant association with VA change (p = 0.12 and p = 0.64, respectively). A lower frequency of ɛ2 and a higher frequency of ɛ4 were observed in Group 3 (2.9 and 25.7%, respectively). VA improvement with more than five ETDRS letters was significantly associated with the presence of the ɛ4 genotype (p = 0.01). CONCLUSIONS: This study demonstrated that carriers of the ApoE ɛ4 polymorphism genotype show demonstrable improvement in VA after treatment with ranibizumab in exudative AMD. ApoE polymorphism identification may be used as a genetic screening to tailor individualized therapeutic approach for optimal treatment in neovascular AMD.

Prognostic value of ERCC1, ERCC2, XRCC1, and TP53 single nucleotide polymorphisms in patients with early-stage non-small cell lung cancer.

Identification of biomarkers used for the prognostic evaluation of non-small cell lung cancer (NSCLC) patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in completely resected NSCLC patients. In total, 130 patients, surgically treated for NSCLC between 2000 and 2012, were included. An analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln, and TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan-Meier method and Cox regression analysis were used. Median age rate was 59.3, ranging between 36 and 78 years. Median relapse-free survival duration (RFS) was found as 46.2 months. In those with ERCC2 CC allele, median RFS was detected as 28.3 months (95 % confidence interval (CI), 20.8-35.8), 46.9 months in those with CT heterozygous (95 % CI, 18.6-75.2), and 80.1 months for those with TT mutant allel (95 % CI, 33.0-127.2). Median RFS was seen to be longer in mutant group and also statistically significant (P = 0.018). Additionally, upon evaluating CC normal group with CT + TT alleles including mutant alleles, median RFS was found as 56.5 months (95 % CI, 24.6-88.4) in CT + TT group, and this was statistically significant (P = 0.005) Also, median RFS was 15.1 months in those including ERCC2 CC allele and 56.5 months in CT + TT allele in the group with no adjuvant treatment (P = 0.001). In conclusion, our study showed that ERCC2/XPD polymorphism is an independent prognostic factor in operated NSCLC patients, and these findings should be supported with prospective studies.

Early Morphokinetic Monitoring of Embryos after Intracytoplasmic Sperm Injection with Fresh Ejaculate Sperm in Nonmosaic Klinefelter Syndrome: A Different Presentation.

The patient was diagnosed with nonmosaic 47, XXY Klinefelter Syndrome with the AZF deletion absent and SRY+. The nonmosaic 47, XXY karyotype was confirmed on a skin biopsy chromosomal analysis. Using only ejaculate motile sperms, 11 oocytes underwent ICSI and were placed rapidly in a time lapse (Embryoscope ©) with a specific culture dish. Biopsies were performed on six embryos on the 3rd day, and numerical chromosomal abnormalities were observed using the FISH test before transfer. PGS results were normal in only two embryos with normal morphokinetics in the Embryoscope. For clinical confirmation of pregnancy, ultrasonographic examination was performed during the 7th week of pregnancy, and two gestational sacs and fetal heart beat were observed.

Whole exome sequencing identifies three novel mutations in ANTXR1 in families with GAPO syndrome.

GAPO syndrome (OMIM#230740) is the acronym for growth retardation, alopecia, pseudoanodontia, and optic atrophy. About 35 cases have been reported, making it among one of the rarest recessive conditions. Distinctive craniofacial features including alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high forehead, mid-facial hypoplasia, hypertelorism, and thickened eyelids and lips make GAPO syndrome a clinically recognizable phenotype. While this genomic study was in progress mutations in ANTXR1 were reported to cause GAPO syndrome. In our study we performed whole exome sequencing (WES) for five affected individuals from three Turkish kindreds segregating the GAPO trait. Exome sequencing analysis identified three novel homozygous mutations including; one frame-shift (c.1220_1221insT; p.Ala408Cysfs*2), one splice site (c.411A>G; p.Gln137Gln), and one non-synonymous (c.1150G>A; p.Gly384Ser) mutation in the ANTXR1 gene. Our studies expand the allelic spectrum in this rare condition and potentially provide insight into the role of ANTXR1 in the regulation of the extracellular matrix.

Recurrent proximal 18p monosomy and 18q trisomy in a family due to a pericentric inversion.

Here, we report on a family with pericentric inversion of chromosome 18 [inv(18)(p11.2q21)] and two recombinants with a duplication of q21 → qter and a deletion of p11.2 → pter regions in a four-generation family. This chromosomal abnormality was inherited in our first patient from the father, while it was transmitted to the second patient from the mother. Array-CGH analysis were used to better characterize duplicated and deleted chromosomal regions and showed no genomic copy number variation (CNV) differences between these two relatives. We discussed genotype-phenotype correlations including previously reported.

[MicroRNAs and lung cancer]. / MikroRNA'lar ve akciger kanseri.

MicroRNAs (miRNAs) are a class of non-coding RNAs that hybridize to mRNAs and induce either translation repression or mRNA cleavage. Patterns of altered miRNA expression in cancer may work as molecular biomarkers for tumor diagnosis, prognosis of disease-specific outcomes, and prediction of therapeutic responses. In addition, miRNAs can serve as specific targets for gene therapies. This review summarizes the current knowledge of miRNAs and their roles in lung cancer.