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Biomedical subjects

D Donnai

Publications and source records attributed to D Donnai.

At least 73 records · Page 4Linked to original sources
PubMed1997

Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome are caused by a deletion in the same region on chromosome 4p 16.3.

Recently, a deletion of chromosome 4pter was found in three patients with Pitt-Rogers-Danks syndrome. We investigated two of these patients, by means of DNA and FISH studies, together with two additional patients with Pitt-Rogers-Danks syndrome, to determine the critical region of the deletion in these patients and to compare this with the critical region in Wolf-Hirschhorn syndrome. All four patients showed terminal deletions of chromosome 4p of different sizes. One of them appeared to have an unbalanced karyotype caused by a cryptic translocation t(4;8) in the mother, resulting in a deletion of chromosome 4pter and a duplication of chromosome 8pter. The localisation of the Wolf-Hirschhorn critical region has been confined to approximately 1 Mb between D4S43 and D4S115. Our study shows that the deletions in four patients with the Pitt-Rogers-Danks syndrome overlap the Wolf-Hirschhorn critical region and extend beyond this in both directions. This study, combined with the fact that our third patient, who was previously described as a Pitt-Rogers-Danks patient, but who now more closely resembles a Wolf-Hirschhorn patient, makes it likely that Pitt-Rogers-Danks and Wolf-Hirschhorn syndromes are different clinical phenotypes resulting from a deletion in the same microscopic region on chromosome 4p16.

Abnormalities, Multiple↗
PubMed1996

Neurofibromatosis/Noonan phenotype: a variable feature of type 1 neurofibromatosis.

Since January 1989 we have ascertained patients with neurofibromatosis type 1 (NF1) as part of our genetic register in the North West of England. This register has now identified 453 affected cases from 235 families. The first 94 individuals were specifically examined for features of the Noonan phenotype. This was present in 12/94 sequentially identified individuals with NF1 including six individuals from three families. However, three cases occurred in a further family, where Noonan syndrome appeared to segregate separately from NF1. We have provided evidence for the chance association of Noonan syndrome and NF1 and that the Noonan phenotype occurs as a feature in some NF1 families. However, there is now little evidence of a separate NF1/Noonan syndrome entity or of NF1 features occurring in classical Noonan syndrome.

Adolescent↗
PubMed1996

X linked hydrocephalus and MASA syndrome.

X linked hydrocephalus and MASA syndrome are clinically related, neurological disorders with an X linked recessive mode of inheritance. Although originally described as distinct entities, their similarity has become apparent as the number of reported families has increased and a high degree of intra- and interfamilial variation in clinical signs noted for both disorders. Consideration of this clinical overlap together with finding that genes for both diseases map to the same chromosomal band (Xq28) led to the hypothesis that they were caused by mutation at the same locus. This was confirmed by identification of mutations in patients with X linked hydrocephalus and MASA syndrome within the gene for neural cell adhesion molecule L1. Here we review the clinical and genetic characteristics of these disorders and the underlying molecular defects in the L1 gene.

Abnormalities, Multiple↗
PubMed1996

Rothmund-Thomson syndrome: two case reports show heterogeneous cutaneous abnormalities, an association with genetically programmed ageing changes, and increased chromosomal radiosensitivity.

Rothmund-Thomson syndrome is a rare, autosomal recessive disorder associated with characteristic cutaneous changes, sparse hair, juvenile cataracts, short stature, skeletal defects, dystrophic teeth and nails, and hypogonadism. Mental retardation is unusual. An increased incidence of certain malignancies has been reported. Clonal or mosaic chromosome abnormalities and abnormalities in DNA repair mechanisms have been reported in some cases. We report two cases of Rothmund-Thomson syndrome, both with intellectual handicap, associated in one with a previously undescribed histological appearance of involved skin, suggesting that the spectrum of abnormalities is even more heterogeneous than previously presumed. Both cases exhibited chromosomal radiosensitivity of lymphocytes which may be an indication of a DNA repair defect. This is the first report of an association between Rothmund-Thomson syndrome and unique, intrinsic, age related skin changes.

Adolescent↗
PubMed1995

Geleophysic dysplasia: a report of three affected boys--prenatal ultrasound does not detect recurrence.

Geleophysic dysplasia is characterized by short stature with short limbs and brachydactyly, a "happy" facial appearance, and joint contractures. Infiltration of heart valves and liver with a mucopolysaccharide-like substance has been demonstrated in some patients. A metabolic pathogenesis is suspected, but has not yet been identified. We report on 3 boys with the condition, 2 of whom are brothers. Serial ultrasound scans were performed on 2 of the cases during pregnancy, but short limbs did not become obvious until after 28 weeks of gestation, making it an uninformative procedure for prenatal diagnosis.

Abnormalities, Multiple↗
PubMed1995

Prenatal diagnosis of Smith-Lemli-Opitz syndrome.

An abnormality in cholesterol synthesis was described recently in the Smith-Lemli-Opitz (SLO) syndrome. Here we describe how the application of this finding has enabled an accurate prenatal diagnosis. We also discuss the possible use of this test in detecting heterozygotes.

Abnormalities, Multiple↗
PubMed1995

The mutational spectrum in Waardenburg syndrome.

One hundred and thirty-four families or individuals with auditory-pigmentary syndromes such as Waardenburg syndrome (WS) or probable neurocristopathies were screened for mutations in the PAX3 and MITF genes. PAX3 mutations were found in 20/25 families with definite Type 1 WS and 1/2 with Type 3 WS, but in none of 23 with definite Type 2 WS or 36 with other neurocristopathies. The PAX3 mutations included substitutions of conserved amino acids in the paired domain or the homeodomain, splice-site mutations, nonsense mutations and frame-shifting insertions or deletions. No phenotype-genotype correlations were noted within WS1 families. With MITF, mutations likely to affect protein function were found in seven families, five of which had definite Type 2 WS. We conclude that Type 1 and Type 3 WS are allelic and are normally caused by loss of function mutations in PAX3; that Type 2 WS is heterogeneous, with about 20% of cases caused by mutations in MITF, and that individuals with auditory, pigmentary or neural crest syndromes which do not fit stringent definitions of Waardenburg syndrome are unlikely to have mutations in either the PAX3 or MITF genes. The molecular pathology of MITF/microphthalmia mutations appears to be different in humans and mice, with gene dosage having more significant effects in humans than in the mouse.

Amino Acid Sequence↗
PubMed1994

Spondylocarpotarsal synostosis syndrome (with or without unilateral unsegmented bar).

Spondylocarpotarsal synostosis syndrome is characterized by autosomal recessive inheritance, failure of normal spinal segmentation causing symmetrical block vertebrae or scoliosis, and lordosis. There is a disproportionately short trunk. Some patients have a unilateral unsegmented bar. Other skeletal changes include carpal synostosis, usually capitate-hamate and lunate-triquetrum. Tarsal synostoses were present in patients in whom the feet were radiographed. Stature is short. The feet are flat. Cleft palate and sensorineural or mixed hearing loss are variable manifestations. We have reviewed the literature and present 6 new patients, 2 of them sibs.

Abnormalities, Multiple↗
PubMed1994

Examination of fetuses after induced abortion for fetal abnormality--a follow-up study.

In the North-Western Region we offer a service to examine fetuses aborted after the diagnosis of fetal abnormalities. Many obstetricians use this service. We examined 343 mid-trimester fetuses over the last 5 years: 215 following an abnormal scan and 128 abnormal amniotic fluid or villus findings. When necessary, investigations were performed. A post-mortem examination was always required. As a result of fetal investigation, the scan diagnosis was modified or refined in 91 cases (42.3 per cent). In three of these cases no fetal abnormality was found. For the fetuses diagnosed as abnormal by amniocentesis or chorionic villus biopsy, in one (0.8 per cent) the pre-termination diagnosis was not confirmed. The results were similar to those of our previous 5-year study except (a) diagnosis of neural tube defects was rarely based on amniocentesis in the present study (2/62, 3.2 per cent) compared with the previous one (32/103, 31 per cent), and (b) renal abnormalities were more often diagnosed in the pre-termination scan in the present study. We conclude that the examination of aborted mid-trimester fetuses by dysmorphologists continues to improve diagnosis, allowing more accurate genetic counselling for the families.

Abortion, Induced↗
PubMed1994

Dysmorphic disorders--an overview.

Clinical delineation of dysmorphic syndromes is important for patient management, family counselling and basic research. Productive areas of research in dysmorphology and developmental biology have included the study of the mouse homologies of human disease. Mutations have been identified in both species in highly conserved 'developmental' genes, and also because of phenotypic similarity of syndromes. Mosaicism--somatic, germline and placental--involving chromosomal aneuploidy, single gene mutations and functional differences between cell lines is an important cause of malformations and syndromes. Many recurrent pattern malformation syndromes of previously unknown cause have now been found to be due to chromosomal microdeletions. Diagnosis has been greatly aided by the molecular cytogenetic technique of fluorescent in situ hybridization.

Animals↗