Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.

Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.

Wolfram Syndrome: A case report of two sisters Wolfram Syndrome: Case report of two sisters.

Purpose: To present a case of two siblings with optic atrophy associated with Wolfram Syndrome.

Observations: Two young adult siblings presented with serious bilateral loss of vision and dyschromatopsia established in early adolescence. They were referred with a presumed diagnosis of Leber's Hereditary Optic Neuropathy.

Corrigendum to "Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles".

[This corrects the article DOI: 10.1155/2018/5706142.].

Mutation Spectrum of the Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles.

Aim: To evaluate the frequency and pattern of disease-associated mutations of gene among Greek patients with presumed Stargardt disease (STGD1).

Materials And Methods: A total of 59 patients were analyzed for mutations using the ABCR400 microarray and PCR-based sequencing of all coding exons and flanking intronic regions. MLPA analysis as well as sequencing of two regions in introns 30 and 36 reported earlier to harbor deep intronic disease-associated variants was used in 4 selected cases.

Case series: Pyramidal cataracts, intact irides and nystagmus from three novel mutations.

Purpose: To investigate the association between novel mutations to bilateral anterior pyramidal congenital cataracts (APyC), complete and intact irides, and nystagmus.

Observations: This is a retrospective observational case series in a multi-center setting with genetic testing. Three female patients were diagnosed with bilateral APyC, intact irides and nystagmus.

MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load.

Mutations in the m.13094T>C MT-ND5 gene have been previously described in three cases of Leigh Syndrome (LS). In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families) and four asymptomatic carriers.

First report of OPA1 screening in Greek patients with autosomal dominant optic atrophy and identification of a previously undescribed OPA1 mutation.

Purpose: To describe the genotype-phenotype correlation in four Greek pedigrees with autosomal dominant optic atrophy (ADOA) and OPA1 mutations.

Methods: Seven patients from four unrelated families (F1, F2, F3, F4) were clinically assessed for visual acuity, color vision, ptosis, afferent pupillary defects, and visual fields and underwent orthoptic assessment, slit-lamp biomicroscopy, and fundus examination to establish their clinical status. Genomic DNA was extracted from peripheral blood samples from all participants.

X-linked adrenoleukodystrophy: are signs of hypogonadism always due to testicular failure?

We present the clinical and hormonal findings of a young male with X-linked adrenoleukodystrophy (X-ALD), with special emphasis on the biochemical and clinical pattern of hypogonadism. A patient, with primary adrenal insufficiency since the age of 5 years, developed progressive neurological symptoms at the age of 29. Diagnosis of X-ALD was established by elevated serum very long chain fatty acids (VLCFAs) and genetic testing.

Novel mutations of the HRAS gene and absence of hotspot mutations of the BRAF genes in oral squamous cell carcinoma in a Greek population.

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world. The phosphatidylinositol 3 kinase (PI3K) signalling pathway has been reported to play an important role in OSCC. Since we have previously detected absence of hotspot PIK3CA gene mutations in the Greek population, we hypothesized that BRAF or HRAS may be activated as upstream effectors of the pathway.

Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene.

The incidence of adrenal involvement in MEN1 syndrome has been reported between 9 and 45%, while the incidence of adrenocortical carcinoma (ACC) in MEN1 patients has been reported between 2.6 and 6%. In the literature data only unilateral development of ACCs in MEN1 patients has been reported.

Absence of hotspot mutations in exons 9 and 20 of the PIK3CA gene in human oral squamous cell carcinoma in the Greek population.

Objective: Phosphatidylinositol-3 kinases (PI3K) are a group of heterodimeric lipid kinases that regulate many cellular processes. Recent studies have reported high frequencies of somatic hotspot mutations in the phosphatidylinositol-3 kinase catalytic alpha (PIK3CA) gene, which encodes for one of these kinases, in several human solid tumors, including oral squamous cell carcinoma (OSCC). The aim of this study was to determine the frequency of hotspot mutations in exons 9 and 20 of the PIK3CA gene in OSCC in the Greek population.

Identification of two novel mutations in the RET proto-oncogene in the same family.

Background: Activating germline mutations of the RET gene cause multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma (FMTC), conditions that are inherited in an autosomal dominant manner. In addition, somatic RET mutations have been identified in a variable proportion (about 30-70%) of sporadic (nonfamilial) MTC cases.

Methods: We describe a Greek family with two novel likely pathogenic sequence variants of the RET gene.

A novel germline mutation of the VHL gene in a Greek family with Von Hippel-Lindau disease.

Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder, caused by mutations of the VHL gene showing a strong genotype-phenotype correlation. The present report concerns a 16-year-old girl with VHL (retinal, spinal cord and cerebellar haemangioblastomas and pancreatic cysts), her father (retinal and spinal cord haemangioblastomas) and the phenotypically healthy mother and younger brother and sister. DNA extraction, PCR and direct sequencing of the VHL entire coding and intronic flanking sequences, were performed according to standard procedures.

Multiple endocrine neoplasia type 2A in two families with the familial medullary thyroid carcinoma associated G533C mutation of the RET proto-oncogene.

Introduction: Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant hereditary disorder, associated with a cluster of germline gain-of-function mutations of the RET proto-oncogene (RET), mainly in exons 10-15. The G533C mutation in exon 8 of the RET is rare and has been mainly related to the familial medullary thyroid carcinoma.

Patients-methods: We describe the RET G533C mutation in exon 8 of the RET in two unrelated female index patients, with MEN2A phenotype, consisting of pheochromocytoma which was the presenting feature and medullary thyroid carcinoma.

Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1.

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene and characterized by the combined occurrence of tumours of the parathyroid glands, the pancreatic islet cells and the anterior pituitary.

Aim: To identify MEN1 gene mutations and characterize clinical manifestations in Greek patients with MEN1.

Patients And Methods: We studied four unrelated index patients with MEN1, 17 relatives and 100 control subjects.

Donor-derived breast cancer in a bone marrow transplantation recipient.

We present the case of a young lady who had been treated for acute myelocytic leukemia at the age of 14 by means of allogeneic bone marrow transplantation, the donor being her sister. At the age of 28 she underwent modified radical mastectomy for invasive breast adenocarcinoma. Genetic analysis revealed chimeric cellular populations on both the tumour and normal tissues of the patient with preponderance of donor-derived cells.

G1738R is a BRCA1 founder mutation in Greek breast/ovarian cancer patients: evaluation of its pathogenicity and inferences on its genealogical history.

We have performed screening in 287 breast/ovarian cancer families in Greece which has revealed that approximately 12% (8/65) of all index patients-carriers of a deleterious mutation in BRCA1 and BRCA2 genes, contain the base substitution G to A at position 5331 of BRCA1 gene. This generates the amino acid change G1738R for which based on a combination of genetic, in silico and histopathological analysis there are strong suggestions that it is a causative mutation. In this paper, we present further evidence suggesting the pathogenicity of this variant.

Greek BRCA1 and BRCA2 mutation spectrum: two BRCA1 mutations account for half the carriers found among high-risk breast/ovarian cancer patients.

127 Greek breast/ovarian cancer families were screened for germline BRCA1/2 mutations by dHPLC followed by direct sequencing. Our results indicated 16 and 5 breast/ovarian cancer families bearing deleterious mutations in the BRCA1 and BRCA2 genes, respectively. Two novel BRCA2 germline mutations (G4X and 3783del10) are reported here for the first time.

Structural analysis and expression profile of a novel gene on chromosome 5q23 encoding a Golgi-associated protein with six splice variants, and involved within the 5q deletion of a Ph(-) CML patient.

We have identified a novel gene, upstream of the cytokine gene cluster region in 5q23-31, residing within one of the most common deleted segments associated with MDS. The novel gene exhibits significant alternative splicing generating at least six splice variants encoding four putative proline-rich protein isoforms, one of which is Golgi-associated. The gene is ubiquitously expressed and conserved among species with the C.