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Biomedical subjects

N Philip

Publications and source records attributed to N Philip.

At least 55 records · Page 3Linked to original sources
PubMed1999

Evaluation of a mutation screening strategy for sporadic cases of ATR-X syndrome.

We report on the evaluation of a strategy for screening for XNP/ATR-X mutations in males with mental retardation and associated dysmorphology. Because nearly half of the mutations in this gene reported to date fall into a short 300 bp region of the transcript, we decided to focus in this region and to extend the mutation analysis to cases with a negative family history. This study includes 21 mentally retarded male patients selected because they had severe mental retardation and a typical facial appearance. The presence of haemoglobin H or urogenital abnormalities was not considered critical for inclusion in this study. We have identified six mutations which represents a mutation detection rate of 28%. This figure is high enough for us to propose this strategy as a valid first level of screening in a selected subset of males with mental retardation. This approach is simple, does not require RNA preparation, does not involve time consuming mutation detection methods, and can thus be applied to a large number of patients at a low cost in any given laboratory.

Adolescent↗
PubMed1999

Angelman syndrome resulting from UBE3A mutations in 14 patients from eight families: clinical manifestations and genetic counselling.

Angelman syndrome (AS) is a neurological disorder with a heterogeneous genetic aetiology. It most frequently results from a de novo interstitial deletion in the 15q11-q13 region, but in a few cases it is caused by paternal uniparental disomy (UPD) or an imprinting mutation. The remaining 20 to 30% of AS patients exhibit biparental inheritance and a normal pattern of allelic methylation in the 15q11-q13 region. In this latter group, mutations in the UBE3A gene have recently been shown to be a cause of AS. Here we describe the phenotypic expression in 14 AS cases involving eight UBE3A mutations. These comprise 11 familial cases from five families and three sporadic cases. Subtle differences from the typical phenotype of AS were found. Consistent manifestations were psychomotor delay, a happy disposition, a hyperexcitable personality, EEG abnormalities, and mental retardation with severe speech impairment. The other main manifestations of AS, ataxia, epilepsy, and microcephaly, were either milder or absent in various combinations among the patients. In addition, myoclonus of cortical origin was frequently observed with severe fits inducing myoclonic seizures. The majority of the patients were overweight. This study showed that ataxia, myoclonus, EEG abnormalities, speech impairment, characteristic behavioural phenotype, and abnormal head circumference are attributable to a deficiency in the maternally inherited UBE3A allele. Furthermore, analysis of mutation transmission showed an unexpectedly high rate of somatic mosaicism in normal carriers. These data have important consequences for genetic counselling.

Adolescent↗
PubMed1999

[Clinical approach to mental retardation of genetic origin].

Etiological investigations of mental deficiencies and their syndromic analysis have greatly progressed with advancing knowledge in the field of genetics and the advent of new technical procedures. Fast diagnostic tests are now available for certain syndromes, particularly those related to micordeletions. Clinical diagnosis remains however the necessary prerequisite for ordering such tests. The clinical examination not only provides a detailed description of the physical condition, but also provides essential information on behavioral and cognitive disorders. Distinctive behavioral patterns observed in some syndromes are suggestive of a "behavioral phenotype". This pattern can be a valuable clue to diagnosis and also allows for early intervention and counselling specifically aimed at dealing with predicted behavioral abnormalities.

Behavior↗
PubMed1999

[Epilepsy in an adult with chromosome 22q11 micro-deletion].

Chromosome 22q11 deletion is a frequent genetic anomaly, recently discovered, responsible for DiGeorge syndrome and velo-cardio-facial syndrome. The spectrum of clinical features is large: dysmorphic syndrome, mental delay, conotroncal cardiopathy; neurologic manifestations are not rare. Case report is a 28 year old man who presented a symptomatic epilepsy caused by stroke, associated with conotroncal cardiopathy, mental delay, hypocalcemia and facial dysmorphy. A cytogenetic study confirmed the chromosome 22q11 deletion.

Adult↗
PubMed1998

Microcephalic osteodysplastic primordial dwarfism Taybi-Linder type: report of four cases and review of the literature.

Microcephalic and osteodysplastic primordial dwarfism (MODP) types I, II, and III were defined by Majewski et al. in 1982. This group of syndromes was characterized by intrauterine growth retardation, microcephaly, and typical facial appearance with prominent nose and micrognathia. Type II was clearly different, both clinically and radiologically, whereas types I and III shared manifestations. Distinction between the latter two was established on the basis of subtle radiological differences. In 1967, Taybi and Linder described another syndrome with microcephalic congenital dwarfism. There is a consensus that MODP type I and III and Taybi-Linder cephaloskeletal dysplasia represent the same disorder. We report on four patients with MODP type Taybi-Linder syndromes, two of whom were born to unrelated but consanguineous parents, while the other two were sibs. Second-trimester prenatal detection by ultrasonography was possible in one case. Consanguinity in two cases and recurrence among sibs are consistent with autosomal recessive inheritance.

Abnormalities, Multiple↗
PubMed1998

CHARGE syndrome: report of 47 cases and review.

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells.

Abnormalities, Multiple↗
PubMed1998

Identification of novel L1CAM mutations using fluorescence-assisted mismatch analysis.

The L1CAM gene, which is located in Xq28 and codes for a neuronal cell adhesion molecule, is involved in three distinct conditions: HSAS (hydrocephalus-stenosis of the aqueduct of Sylvius), MASA (mental retardation, aphasia, shuffling gait, adductus thumbs), and SPG1 (spastic paraplegia). Molecular analysis of the L1CAM gene is labor-intensive because of the size of the coding region, which is fragmented in numerous exons, and because of the great allelic heterogeneity and distribution of the mutations. The FAMA (fluorescent assisted mismatch analysis) method combines the excellent sensitivity of the chemical cleavage method for scanning PCR fragments larger than 1 kb and the power of automated DNA sequencers. In order to optimize this method for L1CAM, we divided the gene into nine genomic fragments, each including three to four exons. These fragments were PCR-amplified using nine sets of primers containing additional rare universal sequences. A second-stage PCR, per formed with the two dye-labeled universal primers, allowed us to generate 1-kb-labeled fragments, which were then submitted to the chemical cleavage analysis. Among 12 French families with HSAS and/or MASA, we identified nine distinct L1CAM mutations, seven of which were novel, and an intronic variation. This study demonstrates that FAMA allows rapid and reliable detection of mutations in the L1CAM gene and thus represents one of the most appropriate methods to provide diagnosis for accurate genetic counseling in families with HSAS, MASA, or SPG1.

Aphasia↗
PubMed1998

Costello syndrome.

Costello syndrome is characterised by postnatal growth deficiency, coarse facies, redundant skin on the neck, palms, soles, and fingers, dark skin, acanthosis nigricans, and papillomata. The natural history evolves in two phases, a severe failure to thrive during the first months contrasting with a normal weight gain in later life. Cardiomyopathy is frequent but other visceral involvement is rare. Mild to moderate mental retardation is usual and most patients exhibit a characteristic sociable and friendly personality. The pathogenesis and molecular basis of the syndrome are unknown and the diagnosis is reliant on clinical expertise. Papillomata represent the most characteristic manifestation but may arise late in life. The peculiar course of the disease, the typical facies, and the ectodermal involvement with loose and hyperpigmented skin are characteristic enough to allow an early diagnosis. Most cases have been sporadic, suggesting de novo dominant mutations.

Abnormalities, Multiple↗
PubMed1998

Physiopathogenic investigations in a case of familial stiff-skin syndrome.

BACKGROUND: Stiff-skin syndrome (SSS) is a rare cutaneous syndrome characterized by stony-hard skin and limitation of joint mobility. Its cause is still unknown. OBJECTIVE: Biological investigations were performed in a new case of SSS. METHODS: Collagen production and DNA biosynthesis were studied from fibroblast culture. Proinflammatory cytokines (TNF-alpha, IL-6 and TGF-beta2) were measured in the patient's serum. Results were compared with pathological findings. RESULTS: Collagen production and DNA biosynthesis were normal whereas the level of circulating cytokines was high. Histological examination of the skin showed mild fibrosis in the dermis whereas the fascia was not thickened. CONCLUSION: Our clinical and biological findings suggest that in this case, cutaneous changes may be related to an inflammatory process rather than to a primary fibroblast defect or a fascial abnormality as previously hypothesized.

Collagen↗
PubMed1998

Neonatal death in Marshall-Smith syndrome.

Marshall-Smith syndrome is characterized by accelerated skeletal maturation, failure to thrive and dysmorphic features. Since 1971, twenty cases of MSS have been reported. We describe another patient with a very early death demonstrating the clinical variability of the syndrome and the importance of systematic X rays of the skeleton for determining the causes of fetal or neonatal death.

Abnormalities, Multiple↗
PubMed1998

[Genetics of agenesis of the corpus callosum].

Agenesis of corpus callosum (ACC) is one of the most common brain malformations observed in humans. It is a heterogeneous malformation, with many etiologies. Isolated ACC is usually sporadic but familial cases have been reported. ACC can complicate numerous polymalformative, either monogenic or chromosomal syndromes. In some of them, for example Aicardi syndrome, Anderman syndrome or acrocallosal syndrome, ACC is a mandatory manifestation. Further identification of the molecular bases of these syndromes will be helpful in understanding the causal heterogeneity of this malformation.

Agenesis of Corpus Callosum↗
PubMed1998

Prenatal ultrasonographic findings in Proteus syndrome.

Proteus syndrome, a disorder which consists of skeletal, hamartomatous and other mesodermal malformations proves to be tremendously variable. Although most of the patients show deformities at birth, the diagnosis is usually made later in life as the phenotype develops over time. We report on the case of a fetus presenting in utero, with a cystic abdominal mass and malposition of the fingers, which was found to have additional features of Proteus syndrome after termination of pregnancy. This case demonstrates that severe cases of Proteus syndrome can be detected prenatally.

Abdominal Neoplasms↗
PubMed1997

Stüve-Wiedemann syndrome and defects of the mitochondrial respiratory chain.

The Stüve-Wiedemann syndrome (SWS) comprises short stature, congenital bowing of the long bones, respiratory distress, and recurrent episodes of unexplained hyperthermia. The skeletal radiographic changes include short and broad long bones, large metaphyses, internal cortical thickening, and angulation primarily of tibiae and femora, but also of humeri and forearm bones. We report 3 cases of SWS from 2 different unrelated consanguineous gypsy families. All 3 cases fulfilled the clinical and radiological criteria of SWS. Two patients died shortly after birth, whereas the third one was alive at the age of one year. Besides hyperthermic episodes, one patient had hyperaminoaciduria, hepatic failure, and megaloblastic anemia which prompted us to investigate mitochondrial respiratory chain in 2 cases. Abnormal results consisting of decreased activities of complex I and IV were found in both. The simultaneous occurrence of both SWS phenotype and abnormal mitochondrial metabolism in two unrelated cases strongly supports the hypothesis of a pathogenetic relationship between the two events. These cases may also be related to recent reports on the effects of the mitochondrial respiratory chain defects on embryogenesis.

Abnormalities, Multiple↗