Neurocutaneous syndromes

Mapping Intimacies ◽

10.1093/med/9780199568741.003.0224 ◽

2018 ◽

Author(s):

Nerissa Jordan

Keyword(s):

Early Childhood ◽

De Novo ◽

Genetic Disorders ◽

Specific Treatment ◽

Diverse Group ◽

De Novo Mutations ◽

Cutaneous Manifestations ◽

Distinct Phenotype ◽

Neurocutaneous Syndromes ◽

Age Range

The neurocutaneous syndromes comprise a diverse group of rare genetic disorders with both neurological and cutaneous manifestations. Each syndrome has a distinct phenotype. Symptoms are variable and depend on the syndrome. Neurocutaneous syndromes often present in childhood or adolescence; for example, tuberous sclerosis typically presents in early childhood. The age range of presentation is broad, depending on the specific condition and severity of expression. The majority are autosomally inherited conditions. De novo mutations can occur. Most neurocutaneous syndromes do not have a specific treatment, and management is predominantly supportive and aimed at symptom reduction and appropriate monitoring. This chapter discusses neurocutaneous syndromes, including their symptoms, demographics, etiologies, natural history, complications, diagnosis, prognosis, and treatment.

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De novo mutations in regulatory elements cause neurodevelopmental disorders

10.1101/112896 ◽

2017 ◽

Cited By ~ 3

Author(s):

Patrick J. Short ◽

Jeremy F. McRae ◽

Giuseppe Gallone ◽

Alejandro Sifrim ◽

Hyejung Won ◽

...

Keyword(s):

Neurodevelopmental Disorders ◽

Developmental Disorders ◽

De Novo ◽

Genetic Disorders ◽

Fetal Brain ◽

Regulatory Elements ◽

De Novo Mutations ◽

Active Elements ◽

Diagnostic Coding ◽

Genome Wide

SummaryDe novo mutations in hundreds of different genes collectively cause 25-42% of severe developmental disorders (DD). The cause in the remaining cases is largely unknown. The role of de novo mutations in regulatory elements affecting known DD associated genes or other genes is essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 DD patients. Here we show that de novo mutations in highly conserved fetal-brain active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant two-fold enrichment of recurrently mutated elements. We estimate that, genome-wide, de novo mutations in fetaLbrain active elements are likely to be causal for 1-3% of patients without a diagnostic coding variant and that only a small fraction (<2%) of de novo mutations in these elements are pathogenic. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasise the importance of combining functional and evolutionary evidence to delineate regulatory causes of genetic disorders.

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Post-transcriptionally impaired de novo mutations contribute to the genetic etiology of four neuropsychiatric disorders

10.1101/175844 ◽

2017 ◽

Author(s):

Fengbiao Mao ◽

Lu Wang ◽

Xiaolu Zhao ◽

Zhongshan Li ◽

Luoyuan Xiao ◽

...

Keyword(s):

Protein Interactions ◽

Rna Binding ◽

De Novo ◽

Rna Binding Proteins ◽

Genetic Disorders ◽

Interaction Network ◽

Neuropsychiatric Disorders ◽

Protein Protein Interactions ◽

De Novo Mutations ◽

Coding Region

AbstractWhile deleterious de novo mutations (DNMs) in coding region conferring risk in neuropsychiatric disorders have been revealed by next-generation sequencing, the role of DNMs involved in post-transcriptional regulation in pathogenesis of these disorders remains to be elucidated. Here, we identified 1,736 post-transcriptionally impaired DNMs (piDNMs), and prioritized 1,482 candidate genes in four neuropsychiatric disorders from 7,748 families. Our results revealed higher prevalence of piDNMs in the probands than in controls (P = 8.19×10−17), and piDNM-harboring genes were enriched for epigenetic modifications and neuronal or synaptic functions. Moreover, we identified 86 piDNM-containing genes forming convergent co-expression modules and intensive protein-protein interactions in at least two neuropsychiatric disorders. These cross-disorder genes carrying piDNMs could form interaction network centered on RNA binding proteins, suggesting a shared post-transcriptional etiology underlying these disorders. Our findings illustrate the significant contribution of piDNMs to four neuropsychiatric disorders, and lay emphasis on combining functional and network-based evidences to identify regulatory causes of genetic disorders.

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Az elsődleges immunhiány-betegségek bőrmanifesztációi

Orvosi Hetilap ◽

10.1556/650.2018.30994 ◽

2018 ◽

Vol 159 (23) ◽

pp. 937-947

Author(s):

Adrienn Erzsébet Bojtor ◽

Miklós Sárdy ◽

László Maródi

Keyword(s):

Early Childhood ◽

Primary Immunodeficiency ◽

Fungal Infections ◽

Genetic Disorders ◽

Primary Immunodeficiency Diseases ◽

Cutaneous Manifestations ◽

Inflammatory Disorders ◽

Dermatological Diseases ◽

Immunodeficiency Diseases

Abstract: Primary immunodeficiency diseases (PIDs) are inherited, genetic disorders. The majority of PIDs are diagnosed in infancy or early childhood, but manifestation in adulthood may also occur. Frequent, recurrent and prolonged infections, which respond poorly to treatment may be heralding signs. PID patients may have increased suspectibility to infections, that mostly affect the sino-pulmonary and intestinal tracts and the skin. PIDs are also frequently associated with autoimmune and inflammatory disorders. Cutaneous manifestations affect 40% to 70% of patients with diagnosed PID. Bacterial and fungal infections of the skin, recurrent pyogen abscesses are common complications. Severe atopy, eczema and erythroderma occurring early in childhood should raise awareness of PID. Cutaneous granulomas, pigment changes and dysplasia of skin, hair, and nails can also be seen frequently in some of these conditions. Here we overview the most frequent dermatological diseases occuring in patients with PID. Orv Hetil. 2018; 159(23): 937–947.

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