Clinically abnormal case with paternally derived partial trisomy 8p23.3 to 8p12 including maternal isodisomy of 8p23.3: a case report

<p>Abstract</p> <p>Background</p> <p>Because of low copy repeats (LCRs) and common inversion polymorphisms, the human chromosome 8p is prone to a number of recurrent rearrangements. Each of these rearrangements is associated with several phenotypic features. We report on a patient with various clinical malformations and developmental delay in connection with an inverted duplication event, involving chromosome 8p.</p> <p>Methods</p> <p>Chromosome analysis, multicolor banding analysis (MCB), extensive fluorescence in situ hybridization (FISH) analysis and microsatellite analysis were performed.</p> <p>Results</p> <p>The karyotype was characterized in detail by multicolor banding (MCB), subtelomeric and centromere-near probes as 46,XY,dup(8)(pter->p23.3::p12->p23.3::p23.3->qter). Additionally, microsatellite analysis revealed the paternal origin of the duplication and gave hints for a mitotic recombination involving about 6 MB in 8p23.3.</p> <p>Conclusion</p> <p>A comprehensive analysis of the derivative chromosome 8 suggested a previously unreported mechanism of formation, which included an early mitotic aberration leading to maternal isodisomy, followed by an inverted duplication of the 8p12p23.3 region.</p

Influence of Reduced Folate Carrier and Aminoimidazole Carboxamide Ribonucleotide Transformylase gene polymorphisms on the efficacy of methotrexate in juvenile idiopathic arthritis

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Derivative chromosome 1 and GLUT1 deficiency syndrome in a sibling pair

<p>Abstract</p> <p>Background</p> <p>Genomic imbalances constitute a major cause of congenital and developmental abnormalities. GLUT1 deficiency syndrome is caused by various de novo mutations in the facilitated human glucose transporter 1 gene (1p34.2) and patients with this syndrome have been diagnosed with hypoglycorrhachia, mental and developmental delay, microcephaly and seizures. Furthermore, 1q terminal deletions have been submitted in the recent reports and the absence of corpus callosum has been related to the deletion between <it>C1orf100 </it>and <it>C1orf121 </it>in 1q44.</p> <p>Results</p> <p>This study reports on a sibling pair with developmental delay, mental retardation, microcephaly, hypotonia, epilepsy, facial dysmorphism, ataxia and impaired speech. Chromosome analysis revealed a derivative chromosome 1 in both patients. FISH and MCB analysis showed two interstitial deletions at 1p34.2 and 1q44. SNP array and array-CGH analysis also determined the sizes of deletions detailed. The deleted region on 1p34.2 encompasses 33 genes, among which is <it>GLUT1 </it>gene (<it>SLC2A1</it>). However, the deleted region on 1q44 includes 59 genes and distal-proximal breakpoints were located in the ZNF672 gene and SMYD3 gene, respectively.</p> <p>Conclusion</p> <p>Haploinsufficiency of <it>GLUT1 </it>leads to GLUT1 deficiency syndrome, consistent with the phenotype in patients of this study. Conversely, in the deleted region on 1q44, none of the genes are related to findings in these patients. Additionally, the results confirm previous reports on that corpus callosal development may depend on the critical gene(s) lying in 1q44 proximal to the <it>SMYD3 </it>gene.</p

Turner sendromlu ergenlerin multidisipliner yaklaşımla psikometrik ve psikososyal açıdan değerlendirilmesi: Ön çalışma

Introduction: The aim of this study is to compare neurocognitive and psychosocial characteristics in adolescents with Turner Syndrome (TS) and age-matched adolescents with short stature (SS) and normal karyotypes. Materials and Methods: Seven patients with TS and 7 patients with SS and normal karyotypes were included in the study. Their comorbid psychopathologies, cognitive functioning, quality of life, self-esteem, emphatic tendencies, mentalizing abilities and coping strategies were investigated. Results: Although the adolescents with SS had higher levels of anxiety and conduct problems, there were no significant differences between the TS and SS groups in terms of comorbid psychopathologies, social cognition skills, quality of life, self-esteem and coping strategies. However, the cognitive functioning of adolescents with TS was found to be lower than both of the adolescents with SS and community samples. Conclusions: According to this preliminary study, anxiety/conduct problems and cognitive functioning of patients with TS should be evaluated in order to prevent subsequent negative outcomes.Giriş: Bu çalışmanın amacı, TS olan ergenler ile kısa boylu ve normal karyotipi olan benzer yaştaki ergenleri nörobilişsel ve psikososyal olarak karşılaştırmaktır. Gereç ve Yöntem: Çalışmaya TS olan yedi hasta ile kısa boylu ve normal karyotipi olan yedi hasta dahil edilmiştir. Eşlik eden psikopatolojiler, bilişsel işlevsellik, yaşam kalitesi, benlik saygısı, empatik eğilimler, zihinselleştirme becerileri ve baş etme stratejileri araştırılmıştır. Bulgular: Kısa boylu ergenlerde anksiyete ve davranım problemleri daha yüksek olmasına karşın, eşlik eden psikopatolojiler, sosyal biliş becerileri, yaşam kalitesi, benlik saygısı ve başetme stratejileri açısından TS olan ergenler ile kısa boylu ergenler arasında önemli bir fark bulunmamıştır. Bununla birlikte, TS olan ergenlerin bilişsel işlevlerinin hem kısa boylu ergenlere hem de toplum örneklemine göre daha düşük olduğu bulunmuştur. Sonuç: Bu ön çalışmaya göre, ileride gelişebilecek olumsuz sonuçları önlemek için TS’li hastalar anksiyete / davranış sorunları ve bilişsel işlevler açısından değerlendirilmelidir

A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategie

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

A Baseline Algorithm For Molecular Diagnosis Of Genetic Eye Diseases: Ophthalmologist’S Perspective

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Anauxetic Dysplasia: A Rare Clinical Entity

Cartilage hair hypoplasia and anauxetic dysplasia spectrum constitute a group of autosomal recessive disorders characterized by variable extent of metaphyseal to spondylometaepiphyseal involvement and various additional clinical features. Within this group, anauxetic dysplasia represents the severe end of the skeletal spectrum. However, extraskeletal features including immunodeficiency, hematological abnormalities, and hair hypoplasia are absent, despite the severe skeletal involvement. This disorder is caused by mutations in the gene encoding ribonuclease mitochondrial RNA-processing complex. We herein report on a patient with anauxetic dysplasia, who presented with severe roto-scoliosis and skeletal findings requiring surgical intervention, and in whom a homozygous RMRP mutation was detected.WoSScopu