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Biomedical subjects

D Heron

Publications and source records attributed to D Heron.

16 recordsLinked to original sources
PubMed2006

Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASD) refer to a broader group of neurobiological conditions, pervasive developmental disorders. They are characterised by a symptomatic triad associated with qualitative changes in social interactions, defect in communication abilities, and repetitive and stereotyped interests and activities. ASD is prevalent in 1 to 3 per 1000 people. Despite several arguments for a strong genetic contribution, the molecular basis of a most cases remains unexplained. About 5% of patients with autism have a chromosome abnormality visible with cytogenetic methods. The most frequent are 15q11-q13 duplication, 2q37 and 22q13.3 deletions. Many other chromosomal imbalances have been described. However, most of them remain undetectable using routine karyotype analysis, thus impeding diagnosis and genetic counselling. METHODS AND RESULTS: 29 patients presenting with syndromic ASD were investigated using a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Eight clinically relevant rearrangements were identified in 8 (27.5%) patients: six deletions and two duplications. Altered segments ranged in size from 1.4 to 16 Mb (2-19 clones). No recurrent abnormality was identified. CONCLUSION: These results clearly show that array comparative genomic hybridisation should be considered to be an essential aspect of the genetic analysis of patients with syndromic ASD. Moreover, besides their importance for diagnosis and genetic counselling, they may allow the delineation of new contiguous gene syndromes associated with ASD. Finally, the detailed molecular analysis of the rearranged regions may pave the way for the identification of new ASD genes.

Adolescent↗
PubMed2006

Maternal origin of a novel C-terminal truncation mutation in CDKL5 causing a severe atypical form of Rett syndrome.

The CDKL5 gene has been implicated in infantile spasms and more recently in a Rett syndrome-like phenotype. We report a case of a young girl presenting generalized convulsions at 10 days of life. Subsequent mutation analysis by denaturing high-performance liquid chromatography of MECP2 and CDKL5 genes revealed heterozygosity for a c.47_48insAGG insertion in exon 1 of MECP2 and heterozygosity for a new nonsense mutation p.Q834X and a new missense variant p.V999M in the CDKL5 gene. Co-segregation analysis showed that the nonsense mutation was a de novo mutation and that the insertion and the missense variant were also found in the asymptomatic mother. In the absence of skewed X inactivation in the mother, it is likely that these last two variants are not pathogenic. Reverse transcription-polymerase chain reaction from lymphoblastoid cells of the patient showed only the transcript without the nonsense and missense variations suggesting decreased stability of mature mRNA by nonsense-mediated decay. These data also suggest an occurrence of the de novo mutation in maternal germ line cells. Moreover, this report reinforces the observation that the CDKL5 phenotype overlaps with Rett syndrome and that CDKL5 gene analysis is recommended in females with a seizure disorder commencing in the first weeks of life.

Base Sequence↗
PubMed2006

Wide clinical variability among 13 new Cockayne syndrome cases confirmed by biochemical assays.

Cockayne syndrome is a multi-systemic, autosomal recessive disease characterised by postnatal growth failure and progressive multi-organ dysfunction. The main clinical features are severe dwarfism (<-2 SD), microcephaly (<-3 SD), psychomotor delay, sensorial loss (cataracts, pigmentary retinopathy, and deafness), and cutaneous photosensitivity. Here, 13 new cases of Cockayne syndrome are reported, which have been clinically diagnosed and confirmed using a biochemical transcription assay. The wide clinical variability, ranging from prenatal features to normal psychomotor development, is emphasised. When cardinal features are lacking, the diagnosis of Cockayne syndrome should be considered when presented with growth retardation, microcephaly, and one of the suggesting features such as enophthalmia, limb ataxia, abnormal auditory evoked responses, or increased ventricular size on cerebral imaging.

Abnormalities, Multiple↗
PubMed2003

Neurological presentation in pediatric patients with congenital disorders of glycosylation type Ia.

OBJECTIVE: Congenital disorders of glycosylation (CDG), formerly called carbohydrate-deficient glycoprotein syndromes, constitute a newly identified group of multisystem disorders characterized by defective glycosylation of N-glycosylated proteins. The objective of this work was to describe precisely neurological findings in patients with type Ia CDG (CDG-Ia) and to compare our results with the literature. STUDY DESIGN: We retrospectively reviewed neurological and neurodevelopmental, neuroimaging, and genetic features in ten patients with CDG-Ia who mainly presented with neurological abnormalities during childhood and therefore were referred to a neuropediatrician or a neurogeneticist. RESULTS: Neurological manifestations had a static clinical course, dominated by mental retardation and cerebellar dysfunction, and acute episodes: stroke-like episodes and seizures. However, microcephaly, retinopathy, and polyneuropathy were progressive. All patients had severe global neurodevelopmental delay: only one was able to walk alone at ten years of age and only one could read. Marked heterogeneity in manifestations and delay of diagnosis was noted across the patients. Cerebellar hypoplasia was found by magnetic resonance imaging in all ten patients and olivopontocerebellar hypoplasia in four patients. As in the literature, there was no clear phenotype-mutation correlation. CONCLUSION: Our findings confirm the importance of a precise and complete description of the neurological and neuroradiological phenotype delineating the phenotype of CDG-Ia to increase the likelihood of diagnosing the disease.

Adolescent↗
PubMed1999

Recurrent nonimmune hydrops fetalis: a rare presentation of sialic acid storage disease.

A case of recurrent hydrops fetalis, diagnosed on second trimester's ultrasonography, has led to the diagnosis of sialic acid storage disease. No classic etiology was found after the first accident. The recurrence in subsequent pregnancy raised the possibility of a storage disease that was confirmed by amniocentesis. The diagnosis of Salla's disease was based on high levels of free sialic acid in amniotic fluid and fetal cells culture and by specific histologic features on fetopathologic examination. Diagnosis of inherited diseases is important because it implies a high risk of recurrence which makes mandatory genetic counseling and prenatal care in subsequent pregnancies.

Adult↗
PubMed1998

Diffuse leukodystrophy in an infant with cytochrome-c oxidase deficiency.

A 25-month-old boy, born to consanguineous parents, had progressive spastic tetraplegia, and increased signal of the white matter on cerebral T2-weighted magnetic resonance imaging indicative of diffuse leukodystrophy. Elevated blood and cerebrospinal fluid lactate levels pointed to a respiratory chain defect. Cytochrome-c oxidase deficiency was demonstrated in cultured skin fibroblasts and skeletal muscle. This report extends the phenotype of COX deficiency in infancy. Systematic study of blood and CSF lactate should be carried out in every infant with leukodystrophy.

Brain↗
PubMed1991

Post consolidation therapy for adult patients with acute myeloid leukaemia.

One hundred and sixteen adult patients aged 14-73 with previously untreated acute myeloid leukaemia received induction and consolidation chemotherapy with daunorubicin, cytosine arabinoside and thioguanine. Two novel approaches to post consolidation therapy have been investigated. Patients aged 50 years or less who had no suitable matched allogeneic donor were considered for autologous bone marrow transplantation (BMT) using bone marrow which had been cultured in vitro for 14 d. Patients over the age of 50 years with normal bone marrow cellularity and peripheral blood count were treated with a single oral dose of busulphan 100 mg/m2 (without BMT rescue) 3 months following the completion of consolidation therapy. Eighty-seven patients (75%) achieved a complete remission. Of 70 patients who completed consolidation therapy, 40 were aged less than or equal to 50 years and 30 were greater than 50 years. Forty-three patients went on to receive post consolidation therapy in first CR (autologous BMT 12, allogeneic BMT 7, busulphan therapy 24). The event-free survival at 4 years was 47% for autologous BMT, 34% for allogeneic BMT and 45% for busulphan-treated patients. The survival for the older cohort of patients who received post consolidation therapy with single dose busulphan therapy was encouraging, and this agent should be considered for future post consolidation strategies.

Acute Disease↗
PubMed1989

Regional odontodysplasia: new histopathological data.

Light microscopy, microradiography, SEM and TEM of 4 tooth follicles in a 12-year-old caucasian girl presenting regional odontodysplasia showed widespread globular dentin, calcifications located in the enlarged pulp chambers, hypoplastic and hypomineralized enamel. Hypomineralized strands were sandwiched between two normal enamel layers, which indicates that amelogenesis, interrupted for a while, has once more become established. The enamel surface was covered with calcoglobules. Numerous rounded calcifications were scattered within the dental follicles. Some of these occurred in microfibrils (possibly oxytalan fibers), distinct from collagen fibers. Calcification of the sheath surrounding epithelial rests was a conspicuous feature. The fibroblasts in contact with calcifications developed numerous cytoplasmic extensions, which suggests that they may have assumed a phagocytosis behaviour.

Child↗
PubMed1983

[Sagittal osteotomy of the horizontal branch of the mandible in the treatment of mandibular retrognathism with severe incisor supraocclusion].

Three patients with mandibular retrognathia and marked incisor supraocclusion were treated by sagittal osteomy of the mandibular body. The technique employed is described, and possible indications in certain cases of this type discussed, these including particularly patients in whom molar articulation must not be modified, and when the height of the lower region of the face contraindicates segmental osteotomy.

Adult↗
PubMed1981

Lipid-induced modulation of opiate receptors in mouse brain membranes.

The binding of [3H] D-Ala-enkephalinamide (DAEA) to crude mitochondrial fractions (P2M) from mouse forebrain was determined after modulation of membrane lipid microviscosity. Lipid fluidization of P2M membranes, following treatment with egg lecithin, resulted in a 50% loss of specific binding of DAEA. Increasing the P2M lipid microviscosity, by incorporation of cholesteryl hemisuccinate (CHS), increased the accessibility of the opiate receptors up to a peak level of 170% which decreased sharply upon further increase in lipid microviscosity. The processes resulting from lipid rigidification may have important implications for aging and for drug addiction.

Animals↗