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Biomedical subjects

N Philip

Publications and source records attributed to N Philip.

At least 19 recordsLinked to original sources
PubMed2006

Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases.

BACKGROUND: Costello syndrome (CS) is a rare multiple congenital abnormality syndrome, associated with failure to thrive and developmental delay. One of the more distinctive features in childhood is the development of facial warts, often nasolabial and in other moist body surfaces. Individuals with CS have an increased risk of malignancy, suggested to be about 17%. Recently, mutations in the HRAS gene on chromosome 11p13.3 have been found to cause CS. METHODS: We report here the results of HRAS analysis in 43 individuals with a clinical diagnosis of CS. RESULTS: Mutations were found in 37 (86%) of patients. Analysis of parental DNA samples was possible in 16 cases for both parents and in three cases for one parent, and confirmed the mutations as de novo in all of these cases. Three novel mutations (G12C, G12E, and K117R) were found in five cases. CONCLUSIONS: These results confirm that CS is caused, in most cases, by heterozygous missense mutations in the proto-oncogene HRAS. Analysis of the major phenotypic features by mutation suggests a potential correlation between malignancy risk and genotype, which is highest for patients with an uncommon (G12A) substitution. These results confirm that mutation testing for HRAS is a reliable diagnostic test for CS.

Abnormalities, Multiple↗
PubMed2006

A novel homozygous MMP2 mutation in a family with Winchester syndrome.

The 2001 International Classification of Constitutional Disorders of Bone has included in the group of multicentric hands and feet osteolysis syndromes three autosomal recessive inherited disorders: Winchester, Torg and nodulosis-arthropathy-osteolysis (NAO) syndromes. Nosographic delineations of these rare syndromes are difficult to define, and there is no consensus. In 2001, two mutations in the matrix metalloproteinase 2 gene (MMP2) have been identified in two families with a NAO phenotype. In a recent study, a homozygous MMP2 mutation has also been identified in a patient presenting with Winchester syndrome. We report the clinical evolution of two sisters with a Winchester phenotype. Clinical review over 23 years provides information on the general evolution of osteolysis and points to an intrafamilial variation with clinical and radiological changes during the patients' life. In both sisters, we identified a new homozygous mutation in the catalytic domain of the MMP2 gene. Our study results are consistent with the involvement of MMP2 in Winchester syndrome and with the hypothesis that Winchester and NAO syndromes are allelic disorders that form a continuous clinical spectrum. At last, our observation emphasizes the interest of molecular analysis in genetic counselling of this consanguineous family.

Adult↗
PubMed2006

Mutations in PHD-like domain of the ATRX gene correlate with severe psychomotor impairment and severe urogenital abnormalities in patients with ATRX syndrome.

Mutations in ATRX are associated with a wide and clinically heterogeneous spectrum of X-linked mental retardation syndromes. The ATRX protein, involved in chromatin remodelling, belongs to the family of SWI/SNF DNA helicases and contains a plant homeodomain (PHD)-like domain. To date, more than 60 different mutations have been reported in ATRX. One of them is recurrent and accounts for 20% of all the reported mutations, whereas all others are private. Most mutations are clustered in the two major functional domains, the helicase and the PHD-like domain. So far, no clear genotype-phenotype correlation has been established, with exception to the rare truncating mutations located at the C-terminal part of the protein, which are consistently associated with severe urogenital defects. In this study, we report the molecular analysis performed in 16 families positive for ATRX. Our findings indicate that, in addition to the previously described mutation 'hotspot' in the PHD-like domain, two other protein sections emerge as minor 'hotspots' in the helicase region encoded by exons 18-20 and 26-29, respectively, gathering 33% of all described mutations. Additionally, based on the clinical data collected for 22 patients from the 16 families, we observe that mutations in the PHD-like domain produce severe and permanent psychomotor deficiency, usually preventing patients from walking, as well as constant urogenital abnormalities, while mutations in the helicase domain lead to delayed but correct psychomotor acquisitions together with mild or absent urogenital abnormalities. In summary, mutations in the helicase domain are associated with milder phenotypes than mutations in the PHD-like domain.

DNA Helicases↗
PubMed2005

Unusual phenotype with progressive vertebral fusion in a girl with an apparently balanced t(10;20)(p11;p13) translocation.

We report the case of a girl presenting with an unusual form of multiple joint fusion. Skeletal abnormalities consisted of radioulnar synostosis and vertebral fusions without any carpal, digital or tarsal involvement, and broad ribs and clavicles. Spinal X-rays were available from age 4 to 21, demonstrating that the spinal involvement was progressive and led to a complete anterior and lateral fusion of vertebrae. A complete sequencing of the NOGGIN gene failed to find any mutation. In addition, this girl was carrier of an apparently balanced reciprocal translocation t(10;20)(p11;p13). We investigated the role of the BMP2A gene as a potential candidate gene. Fluorescence in situ hybridization with YAC probes from chromosome 20 showed that the BMP2A gene was not disrupted by the translocation breakpoint.

Abnormalities, Multiple↗
PubMed2005

Optimisation Issues of High Throughput Medical Data and Video Streaming Traffic in 3G Wireless Environments.

In this paper we describe some of the optimisation issues relevant to the requirements of high throughput of medical data and video streaming traffic in 3G wireless environments. In particular we present a challenging 3G mobile health care application that requires a demanding 3G medical data throughput. We also describe the 3G QoS requirement of mObile Tele-Echography ultra-Light rObot system (OTELO that is designed to provide seamless 3G connectivity for real-time ultrasound medical video streams and diagnosis from a remote site (robotic and patient station) manipulated by an expert side (specialists) that is controlling the robotic scanning operation and presenting a real-time feedback diagnosis using 3G wireless communication links.

Humans↗
PubMed2004

[Progressive spastic paraplegia as a presentation of oculodentodigital syndrome].

Oculodentodigital syndrome (ODD) is a rare congenital disorder which associates eyes and facial abnormalities, defects in teeth enamel and type III syndactyly. The causal genetic defect in this syndrome is still unknown. Some patients with ODD syndrome also manifest spastic paraparesis. In most cases, inheritance is autosomal dominant with variable clinical expression. Herein, we report on a patient with ODD syndrome, who was referred for evaluation of spastic paraplegia. Our observations show that ODD syndrome can be recognized in late adulthood and revealed by spastic paraplegia.

Abnormalities, Multiple↗
PubMed2004

[Andersen syndrome: a particular form of paralysis with cardiac dysrhythmia].

Andersen syndrome includes a clinical triad with periodic paralysis, cardiac arrhythmia and dysmorphic features most often mild but relevant. It is a potassium channelopathy due to mutation of KCJN2 gene coding for Kir 2.1 protein. We report a familial case with mutation R218W of Kir 2.1 and discuss the main phenotypic and genetic aspects of Andersen syndrome. Muscle manifestations are essentially a periodic paralysis most often of hypokaliemic type. Muscle biopsy reveals tubular aggregates but can be normal as it is shown in the same patient in our kindred. Our proband complained of paralytic attacks since childhood and at adult age she demonstrated a mild permanent deficit of pelvic girdle muscles as it has been described in other types of periodic paralysis after a long duration course. Cardiac manifestations may include in a variable manner a long QT syndrome, premature ventricular contractions, complex ventricular ectopy, polymorphic or bidirectional ventricular tachycardia. Imipramine had a positive effect on arrhythmia in our case. Dysmorphic features are often mild and have to be cautiously looked for as a clue to the diagnosis of Andersen syndrome. They can be easily overlooked if not systematically looked for. Clinical expressivity is variable including in the same family. In our observation, the daughter showed a complete triad, early expressed, which allowed the diagnosis. Her father was late diagnosed on ventricular dysrhytmia but without muscle manifestations and dysmorphic features. Since KCJN2 gene mutation identification, locus heterogeneity of Andersen syndrome was shown. Andersen syndrome kindreds without mutations in KCNJ2 were clinically indistinguishable from KCNJ2-associated subjects. KCNJ2 gene encodes the inward rectifier K+ channel Kir2.1 which plays an important role in maintaining membrane potential and during the terminal phase of cardiac action potential repolarization. Several studies showed a dominant negative effect of the mutation on Kir 2.1 channel function.

Adolescent↗
PubMed2004

Kelley-Seegmiller syndrome due to a new variant of the hypoxanthine-guanine phosphoribosyltransferase (I136T) encoding gene (HPRT Marseille).

A patient with hyperuricaemia and gouty arthritis due to a new variant of hypoxanthine-guanine phosphoribosyltransferase is described. The mutation (I136T, HPRT Marseille) is in the phosphoribosylpyrophosphate-binding region of the gene and leads to almost total loss of enzyme activity in erythrocytes, with 5% in lymphocytes. Nevertheless, the patient showed no neurological abnormality.

Arthritis, Gouty↗
PubMed2004

Non-telephone healthcare: the role of 4G and emerging mobile systems for future m-health systems.

The next generation of "m-health technologies" is a new and evolving topic in the areas of telemedical and telecare systems. These technologies involve the exploitation of mobile telecommunication and multimedia technologies to provide better access to healthcare personnel on the move, by removing the key disadvantage of trailing wires in current systems. These technologies provide equal access to medical information and expert care by overcoming the boundaries of separation that exist today between different users of such medical information. A great benefit to all users will be a more efficient use of resources and far greater location independence. In this paper we will address some notes and future trends in these emerging areas and their applications for m-health systems. Especially we will discuss the role of 4G and emerging mobile systems for future m-health systems. The new technologies can make the remote medical monitoring, consulting, and health care more flexible and convenient. But, there are challenges for successful wireless telemedicine, which are addressed in this paper.

Access to Information↗
PubMed2003

Comparison between direct clinical and digital photogrammetric measurements in patients with 22q11 microdeletion.

Thanks to recent advances in imaging and computing technology, photoanthropometry has become an increasingly helpful adjunct to obtain objective clinical evidence of morphologic abnormalities in patients with dysmorphic syndromes. The aim of this study was to evaluate measurements made using a new two-dimensional digital photogrammetry technique by comparison with direct clinical measurements. A total of 14 patients with 22q11 microdeletion were included in this study. There were seven females and seven males between 5 and 38 years of age. Sixteen direct clinical measurements were performed using a graduated anthropometric sliding caliper and angle meter. Photogrammetric measurements were made on digital photographs using a commercially available software package. After calibration to one in situ reference on frontal and profile views, photogrammetric measurements were compared to a total of 14 direct clinical measurements made in the same patients. Findings showed that photogrammetric measurements calibrated to an in situ reference were reliable especially on profile views. No statistical difference was found between 10 of the 14 measurements (P> 0.05) including eight of the nine measurements on profile views and two of the five measurements on frontal views. This study indicates that digital photogrammetry is a useful tool but there is still no reliable standard photographic measurement technique.

Adolescent↗
PubMed2003

CIAS1 mutation in a patient with overlap between Muckle-Wells and chronic infantile neurological cutaneous and articular syndromes.

The Muckle-Wells syndrome is a rare autosomal dominant disorder belonging to the group of hereditary fever syndromes. The chronic infantile neurological cutaneous and articular (CINCA) syndrome is a systemic inflammatory disorder of unknown etiology with neonatal onset. They are considered as two different entities. We report the case of a 36-year-old man suffering since birth from a nonpruritic generalized urticaria, with inflammatory flares, joint manifestations and progressive deafness requiring a bilateral hearing aid. An initial diagnosis of Muckle-Wells syndrome was made. However, the patient had an unusual clinical presentation with slightly dysmorphic facial appearance, clubbing of the fingers, mild mental retardation and papilledema. After a genetic advice, a diagnosis of CINCA syndrome was made. Search for mutations in the CIAS1 gene revealed a new mutation in a heterozygous state. This case report really raises the question of a link between these two inflammatory diseases. Further studies are needed to confirm the involvement of mutations of the CIAS1 gene in CINCA syndrome.

Adult↗