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Biomedical subjects

D Donnai

Publications and source records attributed to D Donnai.

At least 109 records · Page 6Linked to original sources
PubMed1992

Characterization of a YAC containing part or all of the Norrie disease locus.

It has been shown from pulsed-field gel electrophoresis (PFGE) that the monoamine oxidase genes A and B (MAOA & MAOB) and DXS7 loci are physically very close. We have therefore extended studies on their relationship through the characterisation of a 650 kb YAC isolated using L1.28 (recognising the DXS7 locus) as a probe. Restriction mapping of the YAC indicates that it contains both MAOA and MAOB genes in addition to the DXS7 locus. The map derived from the YL1.28-YAC is compatible both with the map from an independently derived YAC carrying MAOA and B genes and with the long range genomic map for the region. A series of subclones prepared from a 'phage library (lambda DASH II) of the YAC have been characterised and have been employed to determine the end point of the deletion of a Norrie disease (NDP) patient who has been shown to lack both DXS7 and MAO coding sequences. The pattern of retention of subclones in the deletion patient place the end point of the deletion within 30-130 kb of the proximal end of the YAC. By combining the data with established recombination analysis, we provide evidence that all or part of the NDP lies in the interval of approximately 250kb within the YAC.

Blindness↗
PubMed1992

Hypoplastic thumbs and hydranencephaly: a new syndrome?

We report a fetus with hypoplastic thumbs and hydranencephaly. The features did not fit well into any syndrome described in the London dysmorphology database, and we suspect this may represent a previously undescribed syndrome, although a diagnosis of XK-aprosencephaly syndrome remains possible.

Abortion, Induced↗
PubMed1992

Unbalanced 13;18 translocation and Williams syndrome.

A 2 1/2 year old girl is reported with a de novo 13;18 unbalanced translocation and the facial features of Williams syndrome, subaortic stenosis, failure to thrive, and developmental delay. This case provides two candidate locations for the underlying molecular pathology of this sporadic syndrome. Williams syndrome is associated with intellectual and growth retardation, infantile feeding problems which may be associated with hypercalcaemia, cardiovascular abnormalities, a friendly, loquacious personality, and a typical facies. The cause is not known and only a few chromosome abnormalities have been reported in patients with the Williams syndrome phenotype. Many papers fail to mention chromosome studies. We report a girl with an unbalanced 13;18 translocation and the Williams syndrome phenotype.

Aortic Valve Stenosis↗
PubMed1992

A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity.

A clinical and genetic study of type 2 neurofibromatosis (NF2) has been carried out in the United Kingdom. Virtually complete ascertainment of cases in the north-west of England was achieved and suggests a population incidence of 1 in 33,000 to 40,000. In the UK as a whole, 150 cases have been identified and been used to study the clinical and genetic features of NF2. The autosomal dominant inheritance of NF2 was confirmed, 49% of cases were assessed as representing new mutations, and the mutation rate was estimated to be 6.5 x 10(-6). Evidence to support a maternal gene effect was found in that age at onset was 18.17 years in 36 maternally inherited cases and 24.5 in 20 paternally inherited cases (p = 0.027). The preponderance of maternally inherited cases was also significant (p = 0.03). Data are presented which suggest that there are two types of NF2, one with later onset and bilateral vestibular schwannomas as the only usual feature, and the other with earlier onset and multiple other tumours. A considerable number of cases did not fall easily into one or other group and other factors such as maternal effect on severity and anticipation need to be considered.

Adolescent↗
PubMed1992

A genetic study of type 2 neurofibromatosis in the United Kingdom. II. Guidelines for genetic counselling.

The major defining features, age at onset of symptoms, and survival in 150 patients with type 2 neurofibromatosis (NF2) have been studied. The mean age at onset was 21.57 years (n = 110) and no cases presented after 55 years of age. Patients presented with symptoms attributable to vestibular schwannomas (acoustic neuroma), cranial meningiomas, and spinal tumours. In 97 cases studied personally by the authors, skin and eye examination were found to be useful to detect early signs of the condition. Examination of the skin is likely to assist in early diagnosis in at least 10% of cases and examination of the eye for a lens opacity or cataract in at least as many again. There are marked interfamilial differences in disease severity and tumour susceptibility. Vestibular schwannomas are not fully penetrant, but the condition is usually expressed in another way. Alteration to the current diagnostic criteria is advocated to cover the lack of provision for new mutations. A screening protocol is proposed and the effect of disease heterogeneity on management is discussed.

Adolescent↗
PubMed1992

Ovarian cancer family and prophylactic choices.

A subject from a family with ovarian cancer who has developed bilateral medullary carcinoma of the breast at the age of 40 is presented. The family is consistent with dominant inheritance of ovarian cancer and 12 female family members at 12.5%, 25%, and 50% risk, including our case, have undergone bilateral prophylactic oophorectomy and been given hormone replacement therapy. Despite the risk of further primary tumours of the breast our patient chose to have treatment with wide excision and radiotherapy. The implications for screening, prophylaxis, and hormone replacement therapy for this family are discussed.

Adult↗
PubMed1992

Fetus with unbalanced translocation involving chromosomes 2 and 11.

We report a fetus with an unbalanced translocation between chromosomes 2 and 11, the product of a paternal balanced reciprocal translocation, fetal karyotype 46, XX, -11, +der(11)t(2;11) (q35;q24.1)pat. The fetus had unusual facial features. The relevance of this case to mapping of the type I Waardenburg syndrome gene is discussed.

Abnormalities, Multiple↗
PubMed1992

Association of autosomal dominant cleft lip and palate and translocation 6p23;9q22.3.

Orofacial clefting (OFC) is genetically complex in that no single gene defect is responsible for all forms. We have identified a family who exhibit autosomal dominant orofacial clefting together with some features of ectodermal dysplasia. In this family there is concordance between these features and an apparently balanced translocation t(6;9)(p23;q22.3) which raises the possibility that a locus for one form of orofacial clefting may be located at one of the translocation breakpoints. Fluorescent in situ hybridization has shown that a candidate gene for OFC, which maps to distal 6p, is located on the derived chromosome 9 in affected individuals from this family. Further characterization of the translocation breakpoints and of their relationship with the candidate gene will determine whether a gene important for normal facial and/or ectodermal development is disrupted in this family.

Adult↗
PubMed1992

A clinical study of type 2 neurofibromatosis.

The clinical features, age at onset of symptoms and survival of 150 patients with type 2 neurofibromatosis were studied. The mean age at onset was 21.57 years (n = 110) and no patients presented after 55 years of age. Patients presented with symptoms attributable to vestibular schwannomas (acoustic neuroma), cranial meningiomas and spinal tumours. In 100 patients studied personally by the authors 44 per cent presented with deafness and this was unilateral in the majority (35/44). Deafness was accompanied by tinnitus in a further 10 per cent and muscle weakness or wasting was the first symptom in 12 per cent. Less common presenting symptoms were seizures (8 per cent), vertigo (8 per cent) numbness and tingling (2 per cent) and blindness (1 per cent). Eleven patients were diagnosed asymptomatically through screening. Café au lait spots occurred in 43 per cent (n = 43) but only one case had six. Skin tumours were detected in 68 per cent (68/100) and 38 per cent (34/90) had an identifiable lens opacity or cataract. The mean age at death in 40 cases was 36.25 years and all but one death was a result of a complication of neurofibromatosis. There are marked inter-family differences in disease severity and tumour susceptibility.

Adult↗
PubMed1991

Family implications of neonatal Gorlin's syndrome.

Two very preterm infants (born at 29 and 25 weeks, respectively) were found to have abnormal ribs. Though this was thought unimportant at the time, it was subsequently shown to indicate that some members of their families had a dominantly inherited risk of developing skin cancer and other serious problems.

Adult↗
PubMed1991

Fetal phenytoin exposure, hypoplastic nails, and jitteriness.

In a prospective study infants born to mothers with epilepsy (n = 61) were found to have an unexpectedly high incidence of congenital anomalies (26/61, 43%) and neonatal conditions (26/61, 43%) compared with controls (0/62, and 6/62, 10%, respectively). There were two neonatal deaths in the study group but none among the controls. Hypoplasia of the finger or toenails was a common congenital anomaly in those infants whose mothers had received phenytoin alone or in combination with other anticonvulsant drugs (11 of 40, 28%). The mean serum phenytoin concentration was higher among mothers of infants with hypoplastic nails than among those with normal nails. Jitteriness was a common neonatal condition affecting infants of epileptic mothers (11 of 61, 18%) but not controls The mean cord serum phenytoin concentrations were similar among jittery and non-jittery infants. At follow up (after excluding one infant with Down's syndrome from the study group) the infants seemed to have developed normally, though one had serious learning difficulties at school. We suggest that hypoplasia of the nails is related to high maternal serum concentrations of phenytoin, and though 18% of infants born to epileptic mothers were jittery compared with no control infants this may not be the result of withdrawal of the drug in all cases.

Abnormalities, Drug-Induced↗
PubMed1991

The non-deletion alpha thalassaemia/mental retardation syndrome: further support for X linkage.

It has previously been suggested that the non-deletion form of the alpha thalassaemia/mental retardation syndrome may be an X linked disorder. We describe four brothers with this syndrome in whom the diagnosis was first suspected because of their characteristic clinical features, although these varied somewhat from one sib to another. The diagnosis was confirmed in each case by showing Hb H inclusions in a proportion of their red blood cells. The identification of four similarly affected boys in this pedigree is consistent with an X linked pattern of inheritance. In support of this, very rare Hb H inclusions could be found in the red blood cells of the mother and one sister who both share some facial features with the affected boys and are presumably carriers of this disorder. This pedigree thus provides further evidence that this is an X linked syndrome and indicates the clinical and haematological variability that may exist even within a single affected family.

Adolescent↗
PubMed1991

De novo ring chromosome 3: a new case with a mild phenotype.

We report an 18 year old female with a de novo ring chromosome 3 found after investigation for short stature. Her karyotype was interpreted as 46,XX, r(3)(p26.2q29). Her phenotype is milder than previously reported cases and illustrates the mild end of the spectrum of the ring chromosome 3 phenotype.

Adolescent↗