Abnormality of the corpus callosum (AbnCC) is etiologically a heterogeneous condition and the prognosis in prenatally diagnosed cases is difficult to predict. The purpose of our research was to ...establish the diagnostic yield using chromosomal microarray (CMA) and exome sequencing (ES) in cases with prenatally diagnosed isolated (iAbnCC) and nonisolated AbnCC (niAbnCC).
CMA and prenatal trio ES (pES) were done on 65 fetuses with iAbnCC and niAbnCC. Only pathogenic gene variants known to be associated with AbnCC and/or intellectual disability were considered.
pES results were available within a median of 21.5 days (9-53 days). A pathogenic single-nucleotide variant (SNV) was identified in 12 cases (18%) and a pathogenic CNV was identified in 3 cases (4.5%). Thus, the genetic etiology was determined in 23% of cases. In all diagnosed cases, the results provided sufficient information regarding the neurodevelopmental prognosis and helped the parents to make an informed decision regarding the outcome of the pregnancy.
Our results show the significant diagnostic and prognostic contribution of CMA and pES in cases with prenatally diagnosed AbnCC. Further prospective cohort studies with long-term follow-up of the born children will be needed to provide accurate prenatal counseling after a negative pES result.
Down syndrome is a genetic disorder caused by the presence of a third copy of chromosome 21, associated with intellectual disabilities. Down syndrome is associated with anomalies of both the nervous ...and endocrine systems. Over the past decades, dramatic advances in Down syndrome research and treatment have helped to extend the life expectancy of these patients. Improved life expectancy is obviously a positive outcome, but it is accompanied with the need to address previously overlooked complications and comorbidities of Down syndrome, including obesity and diabetes, in order to improve the quality of life of Down syndrome patients. In this focused review, we describe the associations between Down syndrome and comorbidities, obesity and diabetes, and we discuss the understanding of proposed mechanisms for the association of Down syndrome with metabolic disorders. Drawing molecular mechanisms through which Type 1 diabetes and Type 2 diabetes could be linked to Down syndrome could allow identification of novel drug targets and provide therapeutic solutions to limit the development of metabolic and cognitive disorders.
Down syndrome (DS) is the most common chromosomal disorder. It is responsible for intellectual disability (ID) and several medical conditions. Although men with DS are thought to be infertile, some ...spontaneous paternities have been reported. The few studies of the mechanism of infertility in men with DS are now dated. Recent research in zebrafish has indicated that overexpression of DYRK1A (the protein primarily responsible for ID in DS) impairs gonadogenesis at the embryonic stage. To better ascertain DYRK1A's role in infertility in DS, we investigated the effect of DYRK1A overexpression in a transgenic mouse model. We found that overexpression of DYRK1A impairs fertility in transgenic male mice. Interestingly, the mechanism in mice differs slightly from that observed in zebrafish but, with disruption of the early stages of spermatogenesis, is similar to that seen in humans. Unexpectedly, we observed hypogonadotropic hypogonadism in the transgenic mice.
Background
Despite recent advances in prenatal genetic diagnosis, medical geneticists still face considerable difficulty in interpreting the clinical outcome of copy‐number‐variant duplications and ...defining the mechanisms underlying the formation of certain chromosomal rearrangements.
Optical genome mapping (OGM) is an emerging cytogenomic tool with proved ability to identify the full spectrum of cytogenetic aberrations.
Methods
Here, we report on the use of OGM in a prenatal diagnosis setting. Detailed breakpoint mapping was used to determine the relative orientations of triplicated and duplicated segments in two unrelated foetuses harbouring chromosomal aberrations: a de novo 15q23q24.2 triplication and a paternally inherited 13q14.2 duplication that overlapped partially with the RB1 gene.
Results
OGM enabled us to suggest a plausible mechanism for the triplication and confirmed that the RB1 duplication was direct oriented and in tandem. This enabled us to predict the pathogenic consequences, refine the prognosis and adapt the follow‐up and familial screening appropriately.
Conclusion
Along with an increase in diagnostic rates, OGM can rapidly highlight genotype–phenotype correlations, improve genetic counselling and significantly influence prenatal management.
The clinical significance of duplications and complex rearrangements is often difficult to ascertain. In this study, we used optical genome mapping in a prenatal diagnosis setting to characterize a 15q23q24.2 triplication and to determine the orientation of a duplication encompassing part of the RB1 gene.
ATP1A3, the gene encoding the α3‐subunit of the Na+/K+‐ATPase pump, has been involved in four clinical neurological entities: (1) alternating hemiplegia of childhood (AHC); (2) rapid‐onset dystonia ...parkinsonism (RDP); (3) CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss) syndrome; and (4) early infantile epileptic encephalopathy. Here, we report on a 34‐year‐old female presenting with a new ATP1A3‐related entity involving a relapsing encephalopathy characterized by recurrent episodes of cerebellar ataxia and altered consciousness during febrile illnesses. The term RECA is suggested – relapsing encephalopathy with cerebellar ataxia. The phenotype of this patient, resembling mitochondrial oxidative phosphorylation defects, emphasizes the possible role of brain energy deficiency in patients with ATP1A3 mutations. Rather than multiple overlapping syndromes, ATP1A3‐related disorders might be seen as a phenotypic continuum.
Down syndrome (DS) is the most common genetic disease at birth; on average, it affects 1 in 700 newborns. The syndrome features cognitive impairment, susceptibility to certain diseases, and (in some ...cases) congenital malformations. Improvements in medical care for people with DS have led to an increase in life expectancy. Furthermore, the systematic provision of specific support during childhood improves cognitive function and autonomy in adulthood. Consequently, patients and their families are now seeking the same rights as healthy people. Access to procreation is an emerging debate. The presumption of infertility in DS is based on a few old studies. Down syndrome appears to cause spermatogenesis defects in men and premature menopause in women. When assisted reproductive technology makes it possible to solve these problems, the question of fertility in DS must be addressed. Without entering into highly controversial ethical considerations related to parenthood for people with DS, we reviewed the literature on fertility in DS and tried to specify the associated genetic risk.
Prenatal Diagnosis of Primrose Syndrome Abdallah, Wael; Spaggiari, Emmanuel; Brisset, Sophie ...
Journal of ultrasound in medicine
43, Številka:
2
Journal Article
Recenzirano
Primrose syndrome is a very rare congenital malformation. Symptoms of this disorder may appear during childhood, but the diagnosis is identified in adulthood in the majority of cases. The prenatal ...diagnosis of Primrose syndrome is not developed in the literature. We present herein a case series of 3 cases with characteristic sonographic features. A dysmorphic metopic suture, downslanting palpebral fissures, a wide forehead, and agenesis of corpus callosum are the main signs. A missense mutation in ZBTB20 identified in whole exome sequencing can confirm the prenatal diagnosis of Primrose syndrome.
Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead ...to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.
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