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T R Cole

Publications and source records attributed to T R Cole.

At least 19 recordsLinked to original sources
PubMed1999

Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.

Inherited mutations in the E-cadherin gene ( CDH1 ) were described recently in three Maori kindreds with familial gastric cancer. Familial gastric cancer is genetically heterogeneous and it is not clear what proportion of gastric cancer susceptibility in non-Maori populations is due to germline CDH1 mutations. Therefore, we screened eight familial gastric cancer kindreds of British and Irish origin for germline CDH1 mutations, by SSCP analysis of all 16 exons and flanking sequences. Each family contained: (i) two cases of gastric cancer in first degree relatives with one affected before age 50 years; or (ii) three or more cases of gastric cancer. Novel germline CDH1 mutations (a nonsense and a splice site) were detected in two families (25%). Both mutations were predicted to truncate the E-cadherin protein in the signal peptide domain. In one family there was evidence of non-penetrance and susceptibility to both gastric and colorectal cancer; thus, in addition to six cases of gastric cancer, a CDH1 mutation carrier developed colorectal cancer at age 30 years. We have confirmed that germline mutations in the CDH1 gene cause familial gastric cancer in non-Maori populations. However, only a minority of familial gastric cancers can be accounted for by CDH1 mutations. Loss of E-cadherin function has been implicated in the pathogenesis of sporadic colorectal and other cancers, and our findings provide evidence that germline CDH1 mutations predispose to early onset colorectal cancer. Thus, CDH1 should be investigated as a cause of inherited susceptibility to both gastric and colorectal cancers.

Adult↗
PubMed1999

Growth in Sotos syndrome.

Although there are several reports on infant and childhood growth in patients with Sotos syndrome, there is little information on the final height achieved and puberty. Growth data on 40 patients (20 female and 20 male) aged 2-31 years were collected. These showed that patients with Sotos syndrome are excessively tall at birth, during infancy, and during childhood. Disproportionately long limbs constitute much of the increase in stature. However, the combination of advanced bone age and early onset of menarche led to a mean (SD) final height of 172.9 (5.7) cm in women. This is within the normal range for the population. Most of the men also attained a final height (mean, 184.3 cm; SD, 6.0) within the normal range, although exceptions were more likely in men than in women. Therefore, these results show that most patients with Sotos syndrome do not require intervention to limit their adult height.

Acromegaly↗
PubMed1999

Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation.

Beckwith-Wiedemann syndrome (BWS) is a human imprinting disorder with a variable phenotype. The major features are anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumours. BWS is genetically heterogeneous and epigenetic changes in the IGF2/H19 genes resulting in overexpression of IGF2 have been implicated in many cases. Recently germline mutations in the cyclin dependent kinase inhibitor gene CDKN1C (p57KIP2) have been reported in a variable minority of BWS patients. We have investigated a large series of familial and sporadic BWS patients for evidence of CDKN1C mutations by direct gene sequencing. A total of 70 patients with classical BWS were investigated; 54 were sporadic with no evidence of UPD and 16 were familial from seven kindreds. Novel germline CDKN1C mutations were identified in five probands, 3/7 (43%) familial cases and 2/54 (4%) sporadic cases. There was no association between germline CDKN1C mutations and IGF2 or H19 epigenotype abnormalities. The clinical phenotype of 13 BWS patients with germline CDKN1C mutations was compared to that of BWS patients with other defined types of molecular pathology. This showed a significantly higher frequency of exomphalos in the CDKN1C mutation cases (11/13) than in patients with an imprinting centre defect (associated with biallelic IGF2 expression and H19 silencing) (0/5, p<0.005) or patients with uniparental disomy (0/9, p<0.005). However, there was no association between germline CDKN1C mutations and risk of embryonal tumours. No CDKN1C mutations were identified in six non-BWS patients with overgrowth and Wilms tumour. These findings (1) show that germline CDKN1C mutations are a frequent cause of familial but not sporadic BWS, (2) suggest that CDKN1C mutations probably cause BWS independently of changes in IGF2/H19 imprinting, (3) provide evidence that aspects of the BWS phenotype may be correlated with the involvement of specific imprinted genes, and (4) link genotype-phenotype relationships in BWS and the results of murine experimental models of BWS.

Beckwith-Wiedemann Syndrome↗
PubMed1999

An apparently new acrocraniofacial syndrome with cranial nerve and visceral anomalies.

We report details of a neonate with cranial bone dysplasia, broad nasal bridge, microphthalmia, optic and olfactory nerve anomalies, pulmonary segmentation defects, polydactyly, abnormally positioned and shaped thumbs, absent mesentery to the gut and streak gonads. Review of the literature and relevant databases does not identify a likely diagnosis.

Abnormalities, Multiple↗
PubMed1997

The neuroimaging findings in Sotos syndrome.

We reviewed the neuroimaging studies of 40 patients with classic Sotos syndrome. The studies consisted of CT scans only in 4 patients and one or more MRI scans in 36 patients. The diagnosis of Sotos syndrome was made using well-established clinical criteria. The neuroimaging studies of each patient were evaluated subjectively by visual inspection and the chief findings were tabulated and grouped into five categories: 1) ventricular abnormalities, 2) extracerebral fluid spaces, 3) midline abnormalities, 4) migrational abnormalities, and 5) others. The most common abnormality of the cerebral ventricles was prominence of the trigone (90%), followed by prominence of the occipital horns (75%) and ventriculomegaly (63%). The supratentorial extracerebral fluid spaces were increased for age in 70% of the patients and the fluid spaces in the posterior fossa were increased in 70% also. A variety of midline abnormalities were noted but anomalies of the corpus callosum were almost universal. Gray matter heterotopias occurred in only 3 (8%) of 36 patients. Periventricular leukomalacia, presumably the result of prenatal or perinatal difficulties and unrelated to the basic condition, was the most common of the miscellaneous other abnormalities noted. The neuroimaging findings of Sotos syndrome are distinct enough to allow differentiation of this syndrome from other mental retardation syndromes with macrocephaly.

Abnormalities, Multiple↗
PubMed1997

Marshall-Smith syndrome: the expanding phenotype.

We report a child of 3 years 9 months with the Marshall-Smith syndrome (MSS), characterised by the typical facial features, developmental delay, and advanced bone age. After the diagnosis was made at 5 months of age, careful observation for respiratory complications and failure to thrive was initiated. By 3 1/2 years of age, although our patient had no life threatening respiratory complications, investigation showed significant upper airway obstruction, which has been successfully treated. Aggressive treatment for failure to thrive has also allowed her to maintain a weight on the 50th centile. The purpose of this report is to suggest that early diagnosis and aggressive management may improve the ultimate prognosis with respect to the respiratory and feeding difficulties seen in this rare syndrome.

Abnormalities, Multiple↗
PubMed1996

Sotos syndrome: evolution of facial phenotype subjective and objective assessment.

Sotos syndrome is characterised by pre- and post-natal growth acceleration, advanced bone age, developmental delay and a typical facial Gestalt. We have evaluated 45 individuals with Sotos syndrome who were between age 1 and 25 years, in order to better define the change in facial appearance over time. In each individual, a thorough assessment was made, serial photographs were reviewed, and a series of anthropometric craniofacial measurements was obtained. These were compared with age- and sex-matched normal standards. Both clinical and anthropometric evaluations show that the facial appearance which most clinical geneticists would regard as "classical" is established early in life. The head is large and dolichocephalic, with a rounded and prominent forehead, accentuated by frontoparietal balding. There is narrowing at the temples, fullness of the cheeks, and tapering to a pointed chin. With time, the normal process of facial change occurs, superimposed on that typical Gestalt. As the face lengthens, the dominance of the forehead diminishes and the chin achieves greater prominence. The mandible is long and narrow inferiorly, square or pointed, but prognathism is rare. In a small proportion of patients, a rounder face early in life may challenge diagnosis, but follow-up of these large newborn and older infants should allow diagnosis by early childhood. Visualisation of pattern profiles at different ages, supplemented by statistical measures of variability and similarity, support the clinical impressions outlined above.

Adolescent↗
PubMed1996

"Song of ourselves": a quantitative history of American autobiographies.

This article highlights the major descriptive findings of an exploratory, quantitative study of American autobiographies published before 1945. Of particular importance for gerontology, age-cohort distributions of autobiographers are graphed, demonstrating that the genre itself has been created predominantly by men and women aged 55 and over. This study suggests that these writers offer scholars a virtually untapped resource for the historical phenomenology of aging.

Aged↗
PubMed1995

Cancer and congenital abnormalities in Asian children: a population-based study from the West Midlands.

Cancer and associated congenital abnormalities were investigated in Muslim and non-Muslim Asian children from the West Midlands. Cancer incidence rates were calculated for Indian (non-Muslim), Pakistani/Bangladeshi (Muslim) and white children diagnosed from 1978 to 1992. Incidence was significantly higher in the Pakistanis, with an age-standardised rate (ASR) of 163 cases per million per year, compared with 115 for Indian and 125 for white children. Among Asian cancer patients, congenital malformations were significantly more common in Muslim (21%) compared with non-Muslim (7%). In Muslims the malformation excess was caused by autosomal recessive and dominant disorders (in 8% and 5% of cases respectively). Cancer malformation/predisposition syndromes were found in 10% of Muslims, compared with 2% of non-Muslims. In 33% of the Muslims with malformations, childhood cancer and a malformation were also present in a close relative. None of the non-Muslims with malformations had a relative with childhood cancer. The cancer excess in Muslims may be partly related to inherited genes causing both malformations and cancer. The prevalence of autosomal recessive disorders may be related to consanguinity, which is common in the Pakistani Muslim population. The high incidence of autosomal dominant disorders may be related to older paternal age at conception, giving rise to spontaneous mutations.

Adolescent↗
PubMed1994

Metacarpophalangeal pattern profile analysis in Sotos and Marfan syndrome.

Patients with Sotos and Marfan syndrome have unusually long metacarpals and phalanges which may make the differential diagnosis difficult in younger children. Using Q-scores, we compared metacarpophalangeal pattern profile (MCPP) analysis in these two syndromes and identified distinct and different pattern profiles. This illustrates that the MCPPs are specific in these syndromes, even at an early age, and not related solely to the unusually long metacarpals and phalanges. For this study we used data from 50 Sotos patients (34 from the United Kingdom and 16 from the Netherlands, with a total of 95 hand films) and 36 Marfan patients (from the Netherlands, with 98 hand films). Of all patients over age 3 years the bone length (including the epiphysis) was determined. The patients under 7 1/2 years (29 Sotos and 12 Marfan) were also measured without inclusion of the epiphysis. The patients measured without epiphysis had a relative short metacarpal 1 (MC1) and long distal phalanx 1 (DPh1) in Sotos syndrome, and a relative long MC1 and short DPh1 in Marfan syndrome. Between age 3 and 7 1/2 years more than 90% of the films could be classified correctly using these two variables. Of the roentgenograms measured with epiphyses, about 80% were classified correctly.

Adolescent↗
PubMed1994

Sotos syndrome: a study of the diagnostic criteria and natural history.

Seventy-nine patients with a provisional diagnosis of Sotos syndrome were clinically assessed, and their photographs between the ages of 1 and 6 years evaluated. These photographs, together with photographs of first degree relatives, also at ages 1 to 6 years, were reviewed by four clinical geneticists. Forty-one probands (but no first degree relatives) were identified in whom the facial gestalt was thought to be characteristic of Sotos syndrome. Comparison of anthropometric measurements, bone age, and developmental delay in these 41 probands showed marked differences between them and the remaining 38 probands, and allowed the formulation of guidelines for the diagnosis of Sotos syndrome. Length was identified as the most significantly increased prenatal parameter. In childhood occipitofrontal head circumference (OFC), height, and weight were all increased. OFC remained above the 97th centile in all but one case throughout childhood and adulthood, whereas height and weight had a tendency to return towards the mean. This 'normalisation' was more pronounced in females and was probably related to their early puberty. Early developmental delay and an advanced bone age, seen in 100% and 84% respectively of study cases, may be invariable in Sotos syndrome, but selection bias and limited data prevented confirmation of this supposition. The authors suggest that facial gestalt, growth pattern, bone age, and developmental delay are the major diagnostic criteria. Using these criteria, no affected first degree relatives were identified. There were few long term medical complications in the probands, but behavioural difficulties caused considerable parental concern.

Abnormalities, Multiple↗
PubMed1993

Decline and fall.

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Geriatrics↗