1,721,030 research outputs found
Transient neonatal diabetes, a disorder of imprinting
No full textTransient neonatal diabetes (TND) is a rare but distinct type of diabetes. Classically, neonates present with growth retardation and diabetes in the first week of life. Apparent remission occurs by 3 months but there is a tendency for children to develop diabetes in later life. Evidence suggests it is the result of overexpression of an imprinted and paternally expressed gene/s within the TND critical region at 6q24. Two imprinted genes, ZAC (zinc finger protein associated with apoptosis and cell cycle arrest) and HYMAI (imprinted in hydatidiform mole) have been identified as potential candidates. Three genetic mechanisms have been shown to result in TND, paternal uniparental isodisomy of chromosome 6, paternally inherited duplication of 6q24, and a methylation defect at a CpG island overlapping exon 1 of ZAC/HYMAI
Nephrocalcinosis and disordered calcium metabolism in two children with SHORT syndrome
No full textReports of SHORT syndrome have, to date, focused on the clinical features which lie at the core of the diagnosis but there has been little by way of report of long-term outcome, either in terms of medical complications or of intellectual development. We now report two children in whom nephrocalcinosis has developed and a third, adult, with similar findings. It may be that clinicians should be looking among cases of unexplained hypercalcaemia for an alternative phenotypic presentation of this short stature syndrom
Transient neonatal diabetes mellitus type 1
No full textTransient neonatal diabetes mellitus type 1 (TNDM1) is a rare but remarkable form of diabetes which presents in infancy, resolves in the first months of life, but then frequently recurs in later life. It is caused by overexpression of the imprinted genes PLAGL1 and HYMAI on human chromosome 6q24. The expression of these genes is normally restricted to the paternal allele as a result of maternal DNA methylation. TNDM1 is not associated with mutation of PLAGL1 or HYMAI, but rather with their overexpression via uniparental disomy, chromosome duplication, or relaxation of imprinting. Study of patients with TNDM1 has provided valuable insights into the causes of imprinting disorders. Over half of patients with maternal hypomethylation at the TNDM1 locus have additional hypomethylation of other maternally methylated imprinted genes throughout the genome, and the majority of these patients have mutations in the transcription factor ZFP57. TNDM1 with maternal hypomethylation has also been observed in patients conceived by assisted reproduction, and in discordant monozygotic twins. The variable clinical features of TNDM1 may be associated with variation in the nature of the underlying epigenetic and genetic mutations, and future study of this disorder is likely to yield further insights not only into the biological mechanisms of imprinting, but also into the contribution of epigenetics to diabete
Images in neonatal medicine. Coat hanger appearances of the ribs: a useful diagnostic marker of paternal uniparental disomy of chromosome 14
No full textQuality of life after repair of tetralogy of Fallot
No full textObjective:
To determine the quality of life in individuals with corrected tetralogy of Fallot. MMethods and subjects:
Questionnaires concerning quality of life were sent to all 87 surviving patients aged between 16 and 40 years who had undergone intracardiac repair of tetralogy of Fallot and follow-up in the Wessex Cardiothoracic Unit, and to 87 age and sex matched controls, with medically treated haemodynamically insignificant ventricular septal defects. Results:
The only significant difference found between the cases and controls was in requirements for schooling, where those with tetralogy of Fallot were more likely to require additional educational help at school (p = 0.044). For all other aspects of quality of life examined by the questionnaire, including social and genetic history, exercise ability, and health related quality of life, no significant differences were found. Different operative techniques, such as transjunctional patching, right ventriculotomy, and previous palliative shunting, did not affect the quality of life of our population with Tetralogy of Fallot, on average twenty years after their surgery, although the range of operative techniques was limited. Neither age at surgery, nor time since surgery, was correlated with measurements of quality of life. Conclusions:
Those who have undergone surgical correction of tetralogy of Fallot have a normal quality of life, with few differences compared to controls
High resolution cytogenetic analysis: a more cost effective approach to subtelomere screening?
No full textCowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers
No full textBACKGROUND: The most commonly reported phenotypes described in patients with PTEN mutations are Bannayan-Riley-Ruvalcaba syndrome (BRRS), with childhood onset, macrocephaly, lipomas and developmental delay, and Cowden Syndrome (CS), an adult-onset condition recognised by mucocutaneous signs, with a risk of cancers, in particular those of the thyroid and breast. It has been suggested that BRRS and CS are the same condition, but the literature continues to separate them and seek a genotype-phenotype correlation. OBJECTIVE: To study the clinical features of patients with known PTEN mutations and observe any genotype-phenotype correlation. METHODS: In total, 42 people (25 probands and 17 non-probands) from 26 families of all ages with PTEN mutations were recruited through the UK clinical genetics services. A full clinical history and examination were undertaken. RESULTS: We were unable to demonstrate a genotype-phenotype correlation. Furthermore, our findings in a 31-year-old woman with CS and an exon 1 deletion refutes previous reports that whole exon deletions are only found in patients with a BRRS phenotype. CONCLUSION: Careful phenotyping gives further support for the suggestion that BRRS and CS are actually one condition, presenting variably at different ages, as in other tumour-suppressor disorders such as neurofibromatosis type 1. This has important counselling implications, such as advice about cancer surveillance, for children diagnosed with BRRS
Hereditary hyperferritinemia cataract syndrome: ocular, genetic, and biochemical findings
No full textPURPOSE: To describe the cataract morphology and genetic and biochemical findings in a four-generation family with hereditary hyperferritinemia cataract syndrome (HHCS).METHODS: Family members of the proband with HHCS were investigated. DNA sequencing was carried out to identify the iron responsive element (IRE) of the L-ferritin gene in affected and non-affected family members. Molecular modeling allowed prediction of the structure of the mutant IRE in affected cases. Serum ferritin and transferrin saturation were determined using standard methods. All family members underwent slit lamp examination by an ophthalmologist to document presence of cataract or lens status. Cataract morphology was documented where present.RESULTS: This family with HHCS had the genetic heterozygous mutation G32C in the IRE of the L-ferritin mRNA. Lens opacities were detectable in young members of the family, and morphology of cataracts was consistent with previous reports. Biochemical testing demonstrated high serum ferritin levels in affected individuals.CONCLUSIONS: The morphology of cataracts in HHCS seems to be similar in all cases. In the heterozygous G32C mutation, the age at onset of cataracts is very early. Greater awareness of this condition among ophthalmologists will lead to effective family counseling of those affected, by genetic testing or simple biochemical tests. Serum ferritin levels can be effectively used to screen for this condition in suspected families
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