The clinical, cytogenetics and molecular characterization of inverted duplication/deletion of chromosome 8p in a boy with mental and motor retardation: Genotype-phenotype correlation in a case report

Background: Rearrangements that occur mainly through the non-allelic homologous recombination (NAHR) during maternal meiosis in short arms of chromosome 8 is relatively associated with various clinical spectrum.Aim: The objective of this study was to report cytogenetics and molecular characterization of a mental and motor retarded boy with short arm of chromosome 8 rearrangements [invdupdel(8p)] in this current case report. Subjects and methods: We report an 11-year-old boy with scoliosis, intellectual disability, mental-motor retardation and characteristic facial features. Agenesis of corpus callosum was detected with brain Magnetic Resonance Imaging (MRI) analysis. Derivative chromosome 8 structure was identified after conventional cytogenetics – karyotype analysis, Multiplex Ligation-Dependent Probe Amplification (MLPA) and Microarray-based Comparative Genomic Hybridization (aCGH) techniques. Genotype-phenotype correlation in the current proband case will be discussed.Results: Case was diagnosed as 46, XY, der (8), del (8) (p23.1) invdup (8) (p11.1-p23.1) by using advanced comparable techniques. Subtelomeric MLPA analysis showed deletion of FBXO25 gene which is located at 8p23.3 locus and FISH with subtelomeric probes for 8p shows also only deleted region. The microarray- CGH profilling showed 7,9 mb deletion for 8p23.1 and 31 mb duplication for 8p11.1 locuses.Conclusion: Results from the current case emphasized that the cases with clinical manifestations of such disorders extremely need to be examined by combined comparable genetics techniques such as; karyotyping, FISH, MLPA and chromosomal microarray for the accurate phenotype – genotype correlation.Keywords: Chromosomal rearrangement, Corpus callosum, Invdupdel(8p)Array-CGH, MLP

Blau syndrome with a rare mutation in exon 9 of NOD2 gene

Blau syndrome is an autosomal dominant rare disease caused by mutations in NOD2 gene. Less than 200 patients published with Blau Syndrome Worldwide. We reported a 41-year old female Turkish patient diagnosed as Blau syndrome. Granulomatous dermatitis and severe headache, as well as recurrent chest and pelvic pain have been present since she was 8 years old. Arthritis started when she was teenage, hypertension diagnosed when she was 20 and other symptoms also occurred during the lifetime (severe preeclampsia, ischemic stroke, recurrent hemiparesis, recurrent-transient-vision-loss and renal-artery-stenosis). Genomic DNA was isolated from peripheral blood and 12 genes sequenced in Autoinflammatory panel on IonTorrent-S5-NGS platform with Parseq-VariFind™AIPassay. NGS analysis showed 107 variants in in the index case, mainly benign with no strong association with Blau syndrome. Additionally, we identified one very rare missense mutation in NOD2 gene (c2803G>A, p.Val935Met) and in silico assessment of the mutation indicated possible pathogenic significance and strong association with Blau syndrome. In addition, we analyzed family members of the index case and identified the same mutation in NOD2 gene. The segregation analysis shows the presence of the same mutant allele in NOD2 gene in the index case affected sister, as well as in her son with arthralgia, while in her non affecter brother we didn’t detect the Val935Met mutation in NOD2 gene. Blau Syndrome is known as a very rare disease, mainly caused by mutations in NOD2 gene. Missense mutation diagnosed in our case could be responsible for the phenotype of the index case. Our results indicate the importance of NGS testing and its major role in the detection of rare mutations that may responsible for the onset of autoinflammatory disorders

Two Siblings with Currarino Syndrome with 7q34 Deletion Due to Maternal t(7;14)(q34;p13)

Currarino syndrome is a rare but well-described form of caudal regression syndrome characterised by anorectal malformations, sacral bony defects and a presacral mass. We present two siblings with Currarino triad due to pure 7q34 deletion but different phenotypes. They had the typical spectrum of sacral agenesis, pre-sacral tumor and anorectal malformations. Interestingly, they have the same genotype but different dysmorphic characteristics. Chromosomal analysis detected that the mother was carrier. To the best of our knowledge, this is the first reported 7q34-14p translocation

The diagnostic accuracy of non-invasive fetal RhD genotyping by using cell-free fetal DNA in maternal plasma

Introduction: The non-invasive prenatal diagnosis of the fetus RhD genotype in RhD incompatibility has a crucial role in the prevention of increased anti-D immunoglobulin therapy for haemolytic diseases in pregnant women carrying RhD negative fetus. It was aimed to detect fetal RhD genotyping by using maternal circulating cell-free DNA in the current study.Methods: Maternal blood samples were collected in different trimester of pregnancies (12-40 weeks) in 12 D-negative mothers. Cell-free fetal DNA was extracted from 2 ml of maternal plasma by an conventional DNA isolation technique (Qiagen, Hilden, Germany) and real-time PCR was performed for genotyping target RhD exons 7 and 10 and GLO genes. Postnatal serological evaluations were performed and the results were confirmed.Results: 6 cases (50 %) were determined D positive and 6 cases (50 %) were determined D negative. All results were also confirmed after birth serologically. Conclusions: In conclusion, the current results showed us the non-invasive target RhD genotyping from cell free fetal DNA from maternal plasma samples have a diagnostic accuracy in RhD incompatibility pregnancies

Is there any increased risk of hypertension, diabetes and cardiac diseases in psoriatic patients with TNF-α G238A and G308A polymorphism?

Introduction : Psoriasis is regarded as a complex autoimmune disease with strong genetic background. Psoriatic patients suffer from many comorbidities including hypertension, diabetes and cardiovascular diseases. Cytokines such as tumor necrosis factor α (TNF-α) may be a key player that triggers psoriasis and diabetes, hypertension and cardiac disease at the same time. Aim: To evaluate genetic variations in the TNF-α region and its association with psoriasis and related comorbidities. Material and methods : The study covered 129 psoriasis patients with three main subgroups with coronary artery disease (n = 41), hypertension (n = 35), and diabetes (n = 21). DNA samples were genotyped for TNF-α G308A and G238A polymorphisms by real-time polymerase chain reaction melting-curve analysis and results were compared statistically. Results : Psoriatic patients with both TNF-α-298 and TNF-α-308 polymorphisms showed no statistically significant increase in the risk of hypertension (OR = 0.425, χ 2 = 1.76, p = 0.18 and OR = 1.87,χ 2 = 1.33, p = 0.25), coronary artery disease (OR = 1.97, χ 2 = 1.91, p = 0.17 and OR = 2.63, χ 2 = 1.35, p = 0.25), or diabetes (OR = 1.35, χ 2 = 0.24, p = 0.62 and OR = 1.53, χ 2 = 0.24, p = 0.62). Conclusions : The current preliminary results suggested that there was no correlation between TNF- promoter polymorphism and diabetes, hypertension and cardiac disease among psoriatic patients in the Turkish population