PubMed Health⌕ Search

Biomedical subjects

T J de Ravel

Publications and source records attributed to T J de Ravel.

At least 19 recordsLinked to original sources
PubMed2005

CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene.

BACKGROUND: CHARGE syndrome is a non-random clustering of congenital anomalies including coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. A consistent feature in CHARGE syndrome is semicircular canal hypoplasia resulting in vestibular areflexia. Other commonly associated congenital anomalies are facial nerve palsy, cleft lip/palate, and tracheo-oesophageal fistula. Specific behavioural problems, including autistic-like behaviour, have been described. The CHD7 gene on chromosome 8q12.1 was recently discovered as a major gene involved in the aetiology of this syndrome. METHODS: The coding regions of CHD7 were screened for mutations in 107 index patients with clinical features suggestive of CHARGE syndrome. Clinical data of the mutation positive patients were sampled to study the phenotypic spectrum of mutations in the CHD7 gene. RESULTS: Mutations were identified in 69 patients. Here we describe the clinical features of 47 of these patients, including two sib pairs. Most mutations were unique and were scattered throughout the gene. All patients but one fulfilled the current diagnostic criteria for CHARGE syndrome. No genotype-phenotype correlations were apparent in this cohort, which is best demonstrated by the differences in clinical presentation in sib pairs with identical mutations. Somatic mosaicism was detected in the unaffected mother of a sib pair, supporting the existence of germline mosaicism. CONCLUSIONS: CHD7 mutations account for the majority of the cases with CHARGE syndrome, with a broad clinical variability and without an obvious genotype-phenotype correlation. In one case evidence for germline mosaicism was provided.

Abnormalities, Multiple↗
PubMed2000

Possible isochromosome 22 leading to trisomy 22.

We describe the first case of trisomy 22 resulting from a monocentric, possible isochromosome 22. The female infant had multiple anomalies including an abnormal face, ambiguous genitalia, and both ventricular and atrial septal defects. Survival was short.

Abnormalities, Multiple↗
PubMed2000

The Pallister-Killian syndrome is reliably diagnosed by FISH on buccal mucosa.

The Pallister-Killian syndrome is a rare disorder, which is clinically diagnosed and usually confirmed by the detection of mosaicism for an isochromosome 12p in fibroblast cultures. To date FISH on buccal mucosa has been used in only three cases and this detected high levels of mosaicism for the isochromosome. We review one previously reported case [Woodman et al. (1995) Genet Couns 6:33-36] and report a further seven clinically suspected cases in which the diagnoses were confirmed by FISH on buccal mucosa, and recommend that this tissue be used routinely for laboratory confirmation. The presence of the isochromosome 12p at levels as low as 1% is acceptable.

Abnormalities, Multiple↗
PubMed2000

Trichorhinophalangeal syndrome type II: case report.

Patients with the trichorhinophalangeal syndrome type II, also known as the Langer-Giedion syndrome, may present to the health care-givers or physicians in various specialties and need to be recognised in order that accurate diagnosis, management and counselling about prognosis and recurrence risks may be carried out. A case of young male with this condition is presented.

Child, Preschool↗
PubMed1999

Hydrolethalus syndrome in a non-Finnish family: confirmation of the entity and early prenatal diagnosis.

We present a family in which the first affected child presented with a 'milder' form of the hydrolethalus syndrome and survived to seven months, and two subsequent pregnancies with typical features detected early by ultrasound evaluation. We propose that the 'milder' cases are indeed true cases of the hydrolethalus syndrome and that allelic variability may be responsible for these 'non-typically Finnish' findings. We also demonstrate that, especially in families where there has been a previously affected fetus, echographic diagnosis can be made in the first trimester, as early as the 11th week of gestation.

Abnormalities, Multiple↗
PubMed1999

Brachydactyly type B with its distinct facies and 'Cooks syndrome' are the same entity.

A sibling pair with brachydactyly type B born to a normal non-consanguineous couple are described and the severity of their condition discussed. It is proposed that a subgroup of individuals with brachydactyly type B principally involving the nails and distal phalanges, and also having distinct facies, might be identical to individuals having 'Cooks syndrome'.

Child↗
PubMed1997

Tetra-amelia and splenogonadal fusion in Roberts syndrome.

Roberts-SC phocomelia syndrome comprises limb deficiencies of variable severity, facial clefts, and other anomalies. Tetra-amelia may also be associated with facial clefts and similar anomalies. We report on a female infant with severe tetra-amelia, micrognathia, cleft palate, splenogonadal fusion, and premature centromere separation. We propose that this represents the severe expression of the Roberts-SC phocomelia syndrome.

Abnormalities, Multiple↗
PubMed1996

Lethal neonatal mandibuloacral dysplasia.

We report on a case of lethal neonatal mandibuloacral dysplasia. Large confluent fontanelles, sparse fine hair and eyebrows, pseudo-exophthalmos, micrognathia, bulbar digits, and short clavicles were present. In addition, we describe for the first time the presence of glandular hypospadias in this disorder. We propose that this neonatally lethal case represents severe expression of mandibuloacral dysplasia.

Clavicle↗
PubMed1996

Novel mutations and polymorphisms in the Fanconi anemia group C gene.

Fanconi anemia (FA) is an autosomal recessive disorder associated with hypersensitivity to DNA cross-linking agents and bone marrow failure. At least four complementation groups have been defined, and the FA group C gene (FAC) has been cloned. We have screened 76 unrelated FA patients of diverse ethnic and geographic origins and from unknown complementation groups for mutations in the FAC gene either by chemical cleavage mismatch analysis or by single-strand conformational polymorphism (SSCP). Five mutations were detected in four patients (5.3%), including two novel mutations (W22X and L496R). Nine polymorphisms were detected, seven of which have not been described previously (663A-->G, L190F, IVS6 + 30C-->T, I312V, V449M, Q465R, and 1974G-->A). Six of the nine polymorphisms occurred in patients or controls from the Tswana or Sotho chiefdoms of South Africa and were not found in 50 unrelated European controls. Restriction site assays were established for all 8 pathogenic mutations identified in the FAC gene to date and used to screen a total of 94 unrelated FA patients. This identified only one other group C patient, who was homozygons for the mutation IVS4 + 4A-->T. This study indicates that the proportion of FA patients from complementation group C is generally likely to be less than 10%. Guidelines for the selection of FA patients for FAC mutation screening are proposed.

Cell Cycle Proteins↗
PubMed1996

First report of CFTR mutations in black cystic fibrosis patients of southern African origin.

Cystic fibrosis (CF) is thought to be rare in the black populations of Africa who have minimal white admixture. Only a few cases have been reported but have not been studied at the molecular level. We report the detection of CFTR mutations in three southern African black patients. One was homozygous for the 3120 + 1G-->A mutation, while the other two were compound heterozygotes each with this mutation on one chromosome. The other mutations were G1249E and a previously unreported in frame 54 bp deletion within exon 17a involving nucleotides 3196-3249 (3196del54). The 3120 + 1G-->A mutation was first described in American black patients and has been shown to be a common mutation in this population (9-14% of CF chromosomes). It was also found in a black CF patient whose father, the 3120 + 1G-->A carrier, is from Cameroon. These data suggest that it is an old mutation which accounts for many of the CFTR mutations in African blacks.

Adult↗
PubMed1995

Maternal origin of extra haploid set of chromosomes in third trimester triploid fetuses.

Twenty-six highly polymorphic markers were used to determine the origin of the extra haploid chromosome set in 6 triploid fetuses of type II phenotype. All had reached the third trimester of pregnancy. The extra set was maternal in origin in all cases, supporting previous research indicating longer in utero survival of maternally-derived triploid fetuses. These findings provide evidence for an instance of genomic imprinting in humans.

Adult↗
PubMed1995

A recurring dominant negative mutation causes autosomal dominant growth hormone deficiency--a clinical research center study.

Familial isolated GH deficiency type II (IGHD-II) is an autosomal dominant disorder that has been previously shown in some patients to be caused by heterogeneous GH gene defects that affect GH messenger RNA (mRNA) splicing. We report here our finding of multiple G-->A transitions of the first base of the donor splice site of IVS 3 (+ 1G-->A) in IGHD II subjects from three nonrelated kindreds from Sweden, North America, and South Africa. This + 1G-->A substitution creates an NlaIII site that was used to demonstrate that all affected individuals in all three families were heterozygous for the mutation. To determine the effect of this mutation on GH mRNA processing, HeLa cells were transfected with expression plasmids containing normal or mutant + 1G-->A alleles, and complementary DNAs from the resulting GH mRNAs were sequenced. The mutation was found to destroy the GH IVS 3 donor splice site, causing skipping of exon 3 and loss of the codons for amino acids 32-71 of the mature GH peptide from the mutant GH mRNA. Our finding of exon 3 skipping in transcripts of the + 1G-->A mutant allele is identical to our previous report of a different sixth base transition (+6T-->C) mutation of the IVS 3 donor splice site that also causes IGHD II. Microsatellite analysis of an affected subjects' DNA from each of the three nonrelated kindreds indicates that the + 1G-->A mutation arose independently in each family. Finding that neither grandparent has the mutation in the first family suggests that it arose de novo in that family. Our data indicate that 1) + 1G-->A IVS 3 mutations perturb GH mRNA splicing and cause IGHD II; and 2) these mutations can present as de novo GHD cases.

Adult↗
PubMed1994

Genetic mapping of the FACC gene and linkage analysis in Fanconi anaemia families.

Fanconi anaemia is an autosomal recessive disorder associated with increased chromosome breakage and progressive bone marrow failure. The gene for complementation group C (FACC) has been cloned and mapped to chromosome 9q22.3, but neither its genetic location nor the proportion of patients belonging to group C is known. We have used a polymorphism within the FACC gene to localise it within a 5 cM interval on chromosome 9q, bounded by D9S196/D9S197 and D9S176. The genes for Gorlin's syndrome and multiple self-healing squamous epitheliomata have also been mapped to this interval. Linkage analysis with the three highly informative microsatellite polymorphisms flanking FACC in 36 Fanconi anaemia families showed that only 8% of families were linked to this locus. This indicates that the genes for the other Fanconi anaemia complementation groups must map to one or more different chromosomal locations. The markers also allowed rapid exclusion of 56% of the families in our panel from complementation group C, thus substantially reducing the number of patients who need to be screened for FACC mutations.

Chromosome Mapping↗