Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis

DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis

karyotyping of patients with psychomotor retardation and epilepsy

WOS: 000410864800230

Clinical utility of of molecular karyotyping

WOS: 000445937400007Purpose: The aim of this study was to investigate molecular karyotyping of epilepsy and intellectual disabilites and to reveal its relationship with these diseases. Materials and Methods: A total of 580 patients with a wide range of clinical problems underwent molecular karyotyping by Affymetrix CytoScan platform included in the study that were presented to Medical Genetics Policlinics of Balcali Hospital and Clinics, Cukurova University Faculty of Medicine. Results: Molecular karyotyping identified 41% microdeletions, 32% duplications and 50% both deletions and duplications in mental retardation patients; 16% microdeletion, 34% duplications and 50% both deletions and duplications in epilepsy patients; and 33.3% microdeletions, 44.4% duplications and 22.2% both deletions and duplications in mental retardation with epilepsy group. In addition, one of epilepsy group with uniparental disomy and 2 marker chromosomes were detected in this study. Conclusion: Our results demonstrate that molecular karyotyping and clinical interpretation by a medical geneticist is efficient in diagnosing chromosomal diseases. Moreover, molecular karyotyping might be more effective as a first tier testing in epilepsy and psychomotor retardation patients

A Rare Double Aneuploidy Case (Down-Klinefelter)

WOS: 000415273800007PubMed ID: 29142768Down's syndrome has its own dysmorphic findings and is accompanied by mental retardation and hypotonia. Klinefelter's syndrome is a syndrome caused by a numerical abnormality that affects male physical and cognitive development. This case reports a unique finding of 48,XXY, + 21 and a current literature review. A 4-month-old male patient presented with typical clinical features of Down's syndrome with hypothyroidism, atrial septal defect, ventricular septal defect, and patent ductus arteriosus without any phenotypic signs of Klinefelter's syndrome

Supernumerary Nipple Children with Different Types of Malignancies

A supernumerary nipple (SN), usually arises within the embryonic milk lines but can also occur in locations such as back, thigh, vulva and neck. The frequency of SN ranges from 0.2% to 5.6% depending on various factors. Although much has been written on the association of SN with other conditions, it still remains as a controversial and speculative area. SN can be associated with several disorders notably urological malformations and urogenital malignancies. To the our knowledge, the association of SN with childhood cancer has rarely been reported before. [Med-Science 2016; 5(1.000): 342-4

eNOS Gene Intron 4 VNTR and Exon 7-G894T Polymorphisms in Turkish Men with Erectile Dysfunction: A Case Control Study

The associations between the gene polymorphisms and erectile dysfunction (ED) are limited

Vitamin D receptor gene polymorphisms, bone mineral density and bone turnover: Fok-I genotype is related to postmenopausal bone mass in essantial hypertension

43rd ERA-EDTA Congress -- JUL 15-18, 2006 -- Glasgow, SCOTLANDWOS: 000239919002232ERA, EDT

A Case with Mental Retardation, Gynecomastia and Dysmorphic Features

The 17 years old boy was diagnosed as Borjeson Forsmann Lehmann Syndrome who was referred to our Genetic Diagnosis Center for his dysmorphic features, obesity, gynecomasty and mental retardation . There are so many diseases in differantial diagnosis of obesity and mental retardation that BFLS is a rare one of them. We aimed to discuss the findings of the patient clinically diagnosed as BFLS within the scope of literature. [Cukurova Med J 2012; 37(1.000): 60-63

No Association between Polymorphisms of Vitamin D and Oxytocin Receptor Genes and Autistic Spectrum Disorder in a Sample of Turkish Children

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social skills and communication with repetitive behaviors. Etiology is still unclear although it is thought to develop with interaction of genes and environmental factors. Oxytocin has extensive effects on intrauterine brain development. Vitamin D, affects neural development and differentiation and contributes to the regulation of around 900 genes including oxytocin receptor gene. In the present study, the contribution of D vitamin receptor and oxytocin receptor gene polymorphisms in the development of ASD in Turkish community was investigated. To our knowledge, this is the first study examining these two associated genes together in the literature. Methods: Eighty-five patients diagnosed with ASD according to DSM-5 who were referred to outpatient clinics of Child and Adolescent Psychiatry of Baskent University and Mersin University and 52 healthy, age and gender-matched controls were included in the present study. Vitamin D receptor gene rs731236 (Taq1), rs2228570 (Fok1), rs1544410 (Bsm1), rs7975232 (Apa1) polymorphisms and oxytocin receptor gene rs1042778 and rs2268493 polymorphisms were investigated using real time polymerase chain reaction method. Results: No significant difference between groups in terms of distribution of genotype and alleles in each of polymorphisms for these genes could be found. Conclusion: Knowledge of genes and polymorphisms associated with the development of ASD may be beneficial for early diagnosis and future treatment. Further studies with larger populations are required to demonstrate molecular pathways which may play part in the development of ASD in Turkey