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Bailliere's Clinical Haematology Mar 1995Feline panleukopenia virus (FPV) and canine parvovirus (CPV) are autonomous parvoviruses which infect cats or dogs, respectively. Both viruses cause an acute disease,... (Review)
Review
Feline panleukopenia virus (FPV) and canine parvovirus (CPV) are autonomous parvoviruses which infect cats or dogs, respectively. Both viruses cause an acute disease, with virus replicating for less than seven days before being cleared by the developing immune responses. The viruses have a broad tropism for mitotically active cells. In neonatal animals the viruses replicate in a large number of tissues, and FPV infection of the germinal epithelium of the cerebellum leads to cerebellar hypoplasia, while CPV may infect the hearts of neonatal pups, causing myocarditis. In older animals the virus replicates systemically, primarily in the primary and secondary lymphoid tissues, and also in the rapidly replicating cells of the small intestinal epithelial crypts. A transient panleukopenia or relative lymphopenia is often observed after FPV or CPV infection, respectively. Whether the reduction in cell numbers in vivo is due to virus replicating in and killing cells, or due to other indirect effects, is not known. However, FPV kills both erythroid and myeloid colony progenitors in in vitro bone marrow cultures, and it has been suggested that virus replication in the myeloid cells in vivo could lead to the reduced neutrophil levels seen after FPV infection of cats.
Topics: Animals; Animals, Newborn; Bone Marrow; Cat Diseases; Cats; Dog Diseases; Dogs; Enteritis; Feline Panleukopenia Virus; Fetal Diseases; Intestine, Small; Leukopenia; Lymphoid Tissue; Mink; Myocarditis; Parvoviridae Infections; Parvovirus, Canine; Raccoons; Virus Replication
PubMed: 7663051
DOI: 10.1016/s0950-3536(05)80232-x -
Brain : a Journal of Neurology Sep 2022Reelin, a large extracellular protein, plays several critical roles in brain development and function. It is encoded by RELN, first identified as the gene disrupted in...
Reelin, a large extracellular protein, plays several critical roles in brain development and function. It is encoded by RELN, first identified as the gene disrupted in the reeler mouse, a classic neurological mutant exhibiting ataxia, tremors and a 'reeling' gait. In humans, biallelic variants in RELN have been associated with a recessive lissencephaly variant with cerebellar hypoplasia, which matches well with the homozygous mouse mutant that has abnormal cortical structure, small hippocampi and severe cerebellar hypoplasia. Despite the large size of the gene, only 11 individuals with RELN-related lissencephaly with cerebellar hypoplasia from six families have previously been reported. Heterozygous carriers in these families were briefly reported as unaffected, although putative loss-of-function variants are practically absent in the population (probability of loss of function intolerance = 1). Here we present data on seven individuals from four families with biallelic and 13 individuals from seven families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Some individuals with monoallelic variants have moderate frontotemporal lissencephaly, but with normal cerebellar structure and intellectual disability with severe behavioural dysfunction. However, one adult had abnormal MRI with normal intelligence and neurological profile. Thorough literature analysis supports a causal role for monoallelic RELN variants in four seemingly distinct phenotypes including frontotemporal lissencephaly, epilepsy, autism and probably schizophrenia. Notably, we observed a significantly higher proportion of loss-of-function variants in the biallelic compared to the monoallelic cohort, where the variant spectrum included missense and splice-site variants. We assessed the impact of two canonical splice-site variants observed as biallelic or monoallelic variants in individuals with moderately affected or normal cerebellum and demonstrated exon skipping causing in-frame loss of 46 or 52 amino acids in the central RELN domain. Previously reported functional studies demonstrated severe reduction in overall RELN secretion caused by heterozygous missense variants p.Cys539Arg and p.Arg3207Cys associated with lissencephaly suggesting a dominant-negative effect. We conclude that biallelic variants resulting in complete absence of RELN expression are associated with a consistent and severe phenotype that includes cerebellar hypoplasia. However, reduced expression of RELN remains sufficient to maintain nearly normal cerebellar structure. Monoallelic variants are associated with incomplete penetrance and variable expressivity even within the same family and may have dominant-negative effects. Reduced RELN secretion in heterozygous individuals affects only cortical structure whereas the cerebellum remains intact. Our data expand the spectrum of RELN-related neurodevelopmental disorders ranging from lethal brain malformations to adult phenotypes with normal brain imaging.
Topics: Adult; Cerebellum; Child; Developmental Disabilities; Humans; Lissencephaly; Mutation; Nervous System Malformations; Reelin Protein
PubMed: 35769015
DOI: 10.1093/brain/awac164 -
Revista Chilena de Pediatria 2016The trisomy 18 syndrome occurs due to the presence of an extra chromosome 18 in most cases. The prevalence in infants is estimated at 1:6000 to 1:8000. Those affected...
INTRODUCTION
The trisomy 18 syndrome occurs due to the presence of an extra chromosome 18 in most cases. The prevalence in infants is estimated at 1:6000 to 1:8000. Those affected have a high mortality rate, only 4% may survive their first year of life. There are few reported cases exceeding five years of age.
OBJECTIVE
The aim of this paper is to report a case of trisomy 18 of long survival with oral cavity features not described in the literature, and to provide information to physicians and paediatricians about aetiology, phenotype, survival and genetic counselling.
CASE REPORT
A 7 year-old female patient with 2 karyotypes performed by lymphocyte culture showing 47XX+18 in all metaphases. She presented with growth deficiency, dysmorphic facies, severe psychomotor retardation and cognitive disability, inability to feed, lack of verbal language, sensorineural hearing loss, ataxia, cerebellar hypoplasia, and genitals with hypoplastic labia majora and minora. In the oral cavity: dome shaped palate, macroglossia, absence of upper central incisors and first upper and lower molars in mouth. X-ray findings showed formation of missing teeth, with late eruption being concluded.
CONCLUSIONS
In cases of trisomy 18 syndrome there is an increased risk of neonatal and infant mortality. The clinical characteristics in utero and in neonates have been well described. Since few cases exceeding five years of age have been reported, the phenotype is yet to be established. In the case being reported we describe oral cavity findings not documented in the literature.
Topics: Child; Chromosomes, Human, Pair 18; Female; Humans; Karyotyping; Mouth Abnormalities; Phenotype; Survival; Trisomy; Trisomy 18 Syndrome
PubMed: 26460083
DOI: 10.1016/j.rchipe.2015.08.006 -
Genetics in Medicine : Official Journal... Dec 2022Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported....
PURPOSE
Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects.
METHODS
Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated.
RESULTS
Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments.
CONCLUSION
A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.
Topics: Child; Humans; Exome; Mutation; Nervous System Malformations; Atrophy; Folate Receptor 1; Kinesins
PubMed: 36305856
DOI: 10.1016/j.gim.2022.08.007 -
Orphanet Journal of Rare Diseases Oct 2020Revesz syndrome (RS) is an extremely rare variant of dyskeratosis congenita (DKC) with only anecdotal reports in the literature. (Review)
Review
BACKGROUND
Revesz syndrome (RS) is an extremely rare variant of dyskeratosis congenita (DKC) with only anecdotal reports in the literature.
METHODS
To further characterize the typical features and natural course of the disease, we screened the English literature and summarized the clinical and epidemiological features of previously published RS cases. In addition, we herein describe the first recorded patient in central Europe.
RESULTS
The literature review included 18 children. Clinical features are summarized, indicating a low prevalence of the classical DKC triad. All patients experienced early bone marrow failure, in most cases within the second year of life (median age 1.5 years; 95% CI 1.4-1.6). Retinopathy occurred typically between 6 and 18 months of age (median age 1.1 years; 95% CI 0.7-1.5). The incidence of seizures was low and was present in an estimated 20% of patients. The onset of seizures was exclusively during early childhood. The Kaplan-Meier estimate of survival was dismal (median survival 6.5 years; 95% CI 3.6-9.4), and none of the patients survived beyond the age of 12 years. Stem cell transplantation (SCT) was performed in eight children, and after a median of 22 months from SCT four of these patients were alive at the last follow up visit.
CONCLUSION
RS is a severe variant of DKC with early bone marrow failure and retinopathy in all patients. Survival is dismal, but stem cell transplantation may be performed successfully and might improve prognosis in the future.
Topics: Bone Diseases, Metabolic; Bone Marrow; Child; Child, Preschool; Dyskeratosis Congenita; Europe; Humans; Infant; Retina
PubMed: 33097095
DOI: 10.1186/s13023-020-01553-y