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Biomedical subjects

M Pembrey

Publications and source records attributed to M Pembrey.

At least 37 records · Page 2Linked to original sources
PubMed1996

Dips on Békésy or audioscan fail to identify carriers of autosomal recessive non-syndromic hearing loss.

Békésy and audioscan sweep audiometry tests were carried out in 24 presumed obligate carriers of autosomal recessive non-syndromic hearing loss and 30 sex and age appropriate controls, with a view to defining the most expedient criteria for dips on either test in respect of possible carrier detection. On Békésy, dips with a minimum depth of 22.5 dB generated the greatest difference between carriers and non-carriers, while on audioscan, the criterion of a minimum dip depth of 15 dB provided the best discriminant. Using these criteria, the prevalence of dips was also evaluated in 8 unaffected siblings and 24 age appropriate control subjects. The findings both in the adult and the paediatric groups do not support the hypothesis that the presence of dips, either on Békésy or audioscan, is linked to the carrier state in ARNSHL.

Acoustic Impedance Tests↗
PubMed1995

Phenotypic manifestations of branchio-oto-renal syndrome.

Branchiootorenal (BOR) syndrome is a variable, autosomal-dominant disorder of the first and second embryonic branchial arches, kidneys, and urinary tract. We describe the phenotype in 45 individuals, highlighting differences and similarities reported in other studies. Characteristic temporal bone findings include cochlear hypoplasia (4/5 of normal size with only 2 turns), dilation of the vestibular aqueduct, bulbous internal auditory canals, deep posterior fossae, and acutely-angled promontories.

Abnormalities, Multiple↗
PubMed1994

Angelman syndrome associated with a maternal 15q11-13 deletion of less than 200 kb.

Angelman syndrome (AS) is a neurogenetic disorder arising from a lack of genetic contribution from the maternal chromosome 15q11-13. To date, the AS critical region has been defined by an inherited deletion of approximately 1.5Mb, spanning the 3-21 (D15S10), LS6-1 (D15S113) and GABRB3 loci. We have identified an individual with the typical features of AS who has a deletion of the maternal chromosome which encompasses LS6-1, but does not extend to either flanking marker. This deletion, initially detected by (CA)n repeat analysis, was further characterised by fluorescence in situ hybridisation (FISH) using cosmids derived from a 260 kb LS6-1 yeast artificial chromosome (YAC). Neither end cosmid from this YAC clone falls within the deletion, suggesting that the minimal AS region is less than 200 kb. We also studied three loci within 15q11-13 which detect parent-of-origin specific DNA methylation imprints, and found that both normal maternal and paternal patterns were present in this patient.

Angelman Syndrome↗
PubMed1994

Fragile-X syndrome in North East Essex: towards systematic screening: clinical selection.

A systematic screening for fragile-X syndrome, using various clinical criteria to preselect for cytogenetic testing, was performed throughout the North East Essex Health District on 1100 people attending three different local services for people with learning disability. The selection procedure used varied from a gestalt impression to head, ear and testis measurement depending on the setting. Fifty-nine males and five females who met the selection criteria went on to have chromosome studies. Of these, 23 males and one female were positive (more than 4% positive cells). They came from 19 families. Whilst the true prevalence of fragile-X syndrome is not known in the district, at a minimum, it contributed 3.2% of the institutionalized males (health authority care), 4.4% of the boys and 2.1% of the girls attending special schools for severe learning disability, 7.9% of the boys attending schools for mild learning disability (Local Education Authority), and 3.5% of men attending the two adult training centres within the district (social services). These figures compare well with the yield from reported surveys in which all individuals without a known diagnosis were tested cytogenetically.

Adolescent↗
PubMed1993

Concordance and recessive inheritance of Leber congenital amaurosis.

Pedigrees were obtained on 43 patients with confirmed Leber congenital amaurosis, a rare form of blindness caused by congenital dysfunction of the retina. All of the pedigrees were consistent with autosomal recessive inheritance and the segregation frequency using classical segregation analysis was 0.24 +/- 0.07. Six of the 7 affected sib pairs were concordant in regards to systemic abnormalities. Despite previous reports that Leber congenital amaurosis can be inherited either as an autosomal dominant or recessive condition, our findings support only an autosomal recessive inheritance of this disorder.

Adolescent↗
PubMed1993

Neuro-otological function in X-linked hearing loss: a multipedigree assessment and correlation with other clinical parameters.

Auditory and vestibular investigations were carried out in 19 affected men and 13 obligate female carriers of 7 pedigrees with nonsyndromic hearing loss segregating as an X-linked trait. In addition, high resolution computerised tomographic scanning was carried out in 24 affected males and 12 obligate female carriers. The neuro-otological results confirm that non syndromic X-linked hearing loss is a clinically heterogeneous condition, but radiological assessment of the cochlea revealed two distinct groups: a normal group, and an abnormal group characterised by a bulbous internal auditory meatus, a dilated facial nerve canal and incomplete separation of the basal coil of the cochlea from the internal auditory meatus. Within a given pedigree there was marked consistency of the presence or absence of the CT scan abnormality in the affected males. One third of the obligate female carriers of the radiologically abnormal pedigrees were shown to have a similar abnormal finding, but as two thirds were normal, radiological examination did not predict carrier status. In the affected men, pure tone audiometric data did not correlate with the radiological abnormality, whereas vestibular function was strikingly correlated, being normal in all but one case in pedigrees with normal radiology and absent, or grossly impaired, in the pedigrees with abnormal radiology. Neuro-otological abnormalities were documented in approximately two thirds of the obligate female carriers, but were insufficiently frequent in occurrence or specific in type to be of predictive value.

Adolescent↗
PubMed1993

Okihiro syndrome: thenar hypoplasia and Duane anomaly in three generations.

We describe a family with five members in three generations affected by Duane anomaly, three of whom also have minor radial ray abnormalities. This appears to be inherited as an autosomal dominant condition and is probably the same condition as that described by Temtamy et al. in 1975 and Okihiro et al. in 1977. One member also has congenital clubbing of the fingers and toes.

Adult↗
PubMed1991

X-linked deafness, stapes gushers and a distinctive defect of the inner ear.

The association of X-linked mixed deafness with stapes gusher has been recognized for 20 years, and imaging studies by polytomography have shown dilatation of the lateral end of the internal auditory meatus (IAM) in some cases. We have made genetic linkage studies in 7 pedigrees in whom deafness was inherited in an X-linked manner. All patients had a full range of audiometric and vestibular function tests. Thin section high resolution CT in two planes was used to assess the state of the middle and inner ears. We found a distinctive inner ear deformity in some of the deaf males characterised not only by a wide bulbous IAM but more importantly, by deficient or absent bone between the lateral end of the IAM and the basal turn of the cochlea. We believe that this results in a communication between the subarachnoid space in the IAM and the perilymph in the cochlea, leading to perilymphatic hydrops and a "gusher" if the stapes is disturbed. Moreover, some of the obligate female carriers seem to have a milder form of the same anomaly associated with slight hearing loss. Genetic studies on some of the deaf males with apparently normal inner ear anatomy suggest a different locus on the X chromosome and hence a different pathogenesis for the deafness.

Audiometry↗
PubMed1989

Follow-up and diagnostic reappraisal of 75 patients with Leber's congenital amaurosis.

We reexamined 75 children in whom Leber's congenital amaurosis had been previously diagnosed. On review, 30 of these patients had an ocular or systemic disorder other than Leber's congenital amaurosis. The most common of these revised diagnoses were congenital stationary night blindness, achromatopsia, infantile-onset retinitis pigmentosa, Joubert's syndrome, Zellweger syndrome, and infantile Refsum's disease. Of the 45 patients with Leber's congenital amaurosis, mental retardation occurred in six patients, and visual deterioration in six patients. Leber's congenital amaurosis should only be diagnosed if other known ocular and systemic disorders have been carefully excluded.

Blindness↗
PubMed1989

The association of Angelman's syndrome with deletions within 15q11-13.

The inheritance of Angelman's syndrome, a disorder characterised by mental retardation, epilepsy, ataxia, and a happy disposition, is debated because affected sibs occur less frequently than expected with autosomal recessive inheritance. After discovering two unrelated patients with a small deletion of the proximal long arm of chromosome 15, 10 further patients with Angelman's syndrome were reassessed. Five had apparently normal karyotypes, four had a deletion within 15q11-13, and one had a pericentric inversion, inv(15)(p11q13) involving the same chromosomal region. In the latter case, the healthy mother had the same pericentric inversion, indicating that the patient also had a submicroscopic mutation on his other chromosome 15. These data map the Angelman locus to 15q11-13 and suggest that de novo visible deletions (associated with a low recurrence risk) and autosomal recessively inherited cases combine to give an overall sib recurrence risk of less than 25%.

Ataxia↗
PubMed1989

Dominantly inherited cleft lip and palate in two families.

Two families with non-syndromic cleft lip and cleft palate are described. The linear pattern of inheritance through several generations is difficult to explain by conventional multifactorial models. The pedigrees strengthen the suggestion that a dominantly inherited mutation exists with a major influence on clefting of the lip and palate alone.

Adult↗
PubMed1988

Genetic prediction in X-linked agammaglobulinaemia.

S21 (DXS17) and pXG12 (DXS94), two probes linked to the locus of X-linked agammaglobulinaemia (XLA), were used for genetic prediction in 13 such families. A method of allowing for nonallelic genetic heterogeneity was demonstrated in the calculation of the genetic risks, specifying a certain proportion of unlinked families. We further estimated the impact due to the uncertainty of the proportion of unlinked families on the final genetic risks in each family and this can be taken into account during genetic counselling.

Agammaglobulinemia↗