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Molecular Evaluation (molecular + evaluation)

Distribution by Scientific Domains

Medical Sciences	42%
Life Sciences	42%

Selected Abstracts

CHARGE syndrome as unusual cause of hypogonadism: endocrine and molecular evaluation

ANDROLOGIA, Issue 5 2010
L. Foppiani
Summary Coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies (CHARGE) syndrome is a genetic syndrome in which hypogonadism is a frequent feature. A causative mutation within the chromodomain helicase DNA-binding protein-7 gene, which plays an important role in the embryonic development, is present in 2/3 of affected patients. We describe the clinical, hormonal and molecular characteristics of a young man from Ecuador who was diagnosed as having CHARGE syndrome at an adult age. The patient showed several phenotypic features of the syndrome, associated with a prepubertal state and cryptorchidism; hypogonadotrophic hypogonadism with undetectable testosterone levels not responsive to hCG testing and severe osteoporosis were ascertained. Molecular evaluation of the CHD7 gene showed the novel frameshift truncating heterozygous mutation p.Tyr1046Glyfs*23 in exon 12. Magnetic resonance imaging revealed mild hypoplasia of the pituitary gland and hypoplasia of the posterior cranial fossa. Parenteral testosterone therapy led to sexual development over time and, in combination with diphophonate therapy and calcium,vitamin D supplementation, significantly improved bone mineralisation. Early proper hormonal treatment of hypogonadism in patients with complex genetic syndromes is important to achieve normal sexual maturation, improve quality of life and avoid significant comorbidities, such as osteoporosis. [source]

Forensic Considerations in Cases of Neurofibromatosis,An Overview

JOURNAL OF FORENSIC SCIENCES, Issue 5 2007
Roger W. Byard M.B.B.S.
Abstract:, Neurofibromatosis types 1 and 2 are inherited neurocutaneous disorders characterized by a variety of manifestations that involve the circulatory system, the central and peripheral nervous systems, the skin, and the skeleton. Significant reduction in lifespan occurs in both conditions often related to complications of malignancy and hypertension. Individuals with these conditions may also be the subject of medicolegal autopsy investigation if sudden death occurs. Unexpected lethal events may be associated with intracranial neoplasia and hemorrhage or brainstem compression. Vasculopathy with fibrointimal proliferation may result in critical reduction in blood flow within the coronary or cerebral circulations, and aneurysmal dilatation may be associated with rupture and life-threatening hemorrhage. An autopsy approach to potential cases should include review of the history/hospital record, liaison with a clinical geneticist (to include family follow-up), a full external examination with careful documentation of skin lesions and nodules, measurement of the head circumference in children, photography, possible radiologic examination, a standard internal autopsy examination, documentation of the effects of previous surgery and/or chemo/radiotherapy, examination for specific tumors, specific examination and sampling of vasculature (renal, cerebral, and cardiac), formal neuropathologic examination of brain and spinal cord, possible examination of the eyeballs, examination of the gastrointestinal tract, histology to include tumors, vessels, gut, and bone marrow, toxicological testing for anticonvulsants, and sampling of blood and tissue for possible cytogenetic/molecular evaluation if required. [source]

Species in the genus Turritopsis (Cnidaria, Hydrozoa): a molecular evaluation

JOURNAL OF ZOOLOGICAL SYSTEMATICS AND EVOLUTIONARY RESEARCH, Issue 1 2007
M. P. Miglietta
Abstract Mitochondrial ribosomal gene sequences were used to investigate the status of several populations of hydromedusae belonging to the genus Turritopsis (family Oceaniidae). Several nominal species have been described for this genus, but most of them had been synonymized and attributed to one cosmopolitan species, Turritopsis nutricula. A recent revision based on morphological and reproductive characters, however, has shown that many different populations can be distinguished and that several of the nominal Turritopsis species are likely valid biological species. Our investigation using molecular sequence data of 16S mitochondrial gene confirms these results. The Mediterranean Turritopsis must be attributed to Turritopsis dohrnii and the Turritopsis of New Zealand must be referred to Turritopsis rubra. The situation of the Japanese Turritopsis is more complex, though all sampled populations are clearly distinct from T. nutricula, a species likely confined to the Western Atlantic. The Japanese Turritopsis fall into three widely separated lineages. One of them, corresponding likely to Turritopsis pacifica, is closely related to T. rubra. A second clade, which potentially represents an as yet undescribed species, produces smaller medusae than T. pacifica and is morphologically distinguishable from it. Finally, a third group was distinguished by a single haplotype sequence that is identical with a Mediterranean sample of T. dohrnii. It is postulated that the last group of Japanese Turritopsis is likely a recent introduction, most probably by human activity. A survey of all known and potentially valid Turritopsis species is given in table format to facilitate identifications and future revisory work. Sommario Sequenze del gene mitocondriale 16S sono state utilizzate per studiare lo stato tassonomico di idroidi appartenenti al genere Turritopsis (Famiglia Oceaniidae). In letteratura, tra le numerose specie nominali di TurritoSPSis descritte, molte di queste sono state successivamente messe in sinonimia e attribuite ad un'unica specie cosmopolita, Turritopsis nutricula. Una recente revisione, basata su dati morfologici e caratteri riproduttivi, ha comunque mostrato che diverse popolazioni di Turritopsis possono essere distinte in numerose specie nominali e probabilmente rappresentano valide specie biologiche. Il presente studio conferma questa recente interpretazione, mediante lo studio di sequenze molecolari del gene 16S. La popolazione mediterranea di Turritopsisè ora attribuita a T. dohrnii, mentre la popolazione neozelandese va ascritta alla specie T. rubra. La situazione nei mari giapponesi si presenta piu' complessa, sebbene tutte le popolazioni ivi campionate siano chiaramente distinte da T. nutricula, la quale risulta confinata unicamente all'Atlantico Orientale. Le sequenze ottenute da esemplari di Turritopsis provenienti dal Giappone formano tre cladi ben distinti. Uno di essi corrisponde a Turritopsis pacifica. Un secondo clade è costituito da popolazioni che producono meduse piu' piccole rispetto a Turritopsis pacifica ed e' dunque anche morfologicamente separato. Un terzo gruppo e' rappresentato da un solo aplotipo identico alle popolazioni mediterranee di T. dohrnii. La presenza di quest'ultimo gruppo di Turritopsis in Giappone e' molto probabilmente il risultato di un'introduzione recente, in seguito ad attività umana. Per facilitare futuri lavori di revisione, è inoltre presentata tavola che riassume le caratteristiche di tutte le specie di Turritopsis conosciute e potenzialmente valide. La tavola cerca di integrare i dati morfologici e riproduttivi già noti e dei dati molecolari ottenuti con questo studio. [source]

Current recommendations for the molecular evaluation of newly diagnosed holoprosencephaly patients,,

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010
Daniel E. Pineda-Alvarez§
Abstract Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain in humans and is typically characterized by different degrees of hemispheric separation that are often accompanied by similarly variable degrees of craniofacial and midline anomalies. HPE is a classic example of a complex genetic trait with "pseudo"-autosomal dominant transmission showing incomplete penetrance and variable expressivity. Clinical suspicion of HPE is typically based upon compatible craniofacial findings, the presence of developmental delay or seizures, or specific endocrinological abnormalities, and is then followed up by confirmation with brain imaging. Once a clinical diagnosis is made, a thorough genetic evaluation is necessary. This usually includes analysis of chromosomes by high-resolution karyotyping, clinical assessment to rule-out well recognized syndromes that are associated with HPE (e.g., Pallister-Hall syndrome, Smith-Lemli-Opitz syndrome and others), and molecular studies of the most common HPE associated genes (e.g., SHH, ZIC2 and SIX3). In this review, we provide current step-by-step recommendations that are medically indicated for the genetic evaluation of patients with newly diagnosed HPE. Moreover, we provide a brief review of several available methods used in molecular diagnostics of HPE and describe the advantages and limitations of both currently available and future tests as they relate to high throughput screening, cost, and the results that they may provide. Published 2010 Wiley-Liss, Inc. [source]

A New De Novo Missense Mutation in Connexin 26 in a Sporadic Case of Nonsyndromic Deafness

THE LARYNGOSCOPE, Issue 5 2007
Paola Primignani PhD
Abstract Objectives: Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic recessive deafness or dominant hearing loss (HL) with or without keratoderma. The objective was to perform a molecular evaluation to establish the inherited pattern of deafness in the sporadic cases afferent to our center. Methods: The subject was a 2-year-old Italian girl with nonsyndromic early onset HL. We performed DNA sequencing of the GJB2 gene and deletion analysis of the GJB6 gene in all family members. Results: Direct sequencing of the gene showed a heterozygous C,G transition at nucleotide 172 resulting in a proline to alanine amino acid substitution at codon 58 (P58A). The analyses indicate that the P58A mutation appeared de novo in the proband with a possible dominant effect. Conclusions: This mutation occurs in the first extracellular domain (EC1), which seems to be very important for connexon-connexon interaction and for the control of voltage gating of the channel. The de novo occurrence of an EC1 mutation in a sporadic case of deafness is consistent with the assumption that P58A can cause dominant HL. [source]

CHARGE syndrome as unusual cause of hypogonadism: endocrine and molecular evaluation

Facioscapulohumeral muscular dystrophy: epidemiological and molecular study in a north-east Italian population sample

CLINICAL GENETICS, Issue 6 2009
ML Mostacciuolo
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease associated with a partial deletion on chromosome 4q35. Few relevant investigations have been reported on its epidemiology and were essentially based on clinical diagnosis, having been performed before recognition of the molecular mutation. We report an epidemiological survey on FSHD patients, in which the diagnosis was obtained by combined clinical and molecular evaluation. The survey concerned the north-east Italian province of Padova, an area of 871,190 inhabitants (1 January 2004). We identified 40 patients affected by FSHD based on clinical diagnosis. In 33 of them, the EcoRI fragment size in the 4q35 region ranged from 14 to 35 kb. Four other patients belonging to the same family harbored a 38-kb fragment. In these four cases, the relationship between the borderline deletion with the mild FSHD phenotype was corroborated by additional haplotype reconstruction and segregation analysis. Interestingly, the same mild facial-sparing clinical pattern was apparent only in one other patient with an EcoRI fragment of 32 kb, suggesting that this unusual FSHD phenotype may be due to very small 4q35 deletions. On the whole, estimating a prevalence rate of 44 × 10,6, our survey confirmed FSHD as one of the most frequent neuromuscular disorders in Western populations. [source]