A Novel Homozygous p.R1105X Mutation of the AP4E1 Gene in Twins with Hereditary Spastic Paraplegia and Mycobacterial Disease

Kong, Xiao‐Fei; Bousfiha, Aziz; Rouissi, Aida; Itan, Yuval; Abhyankar, Avinash; Bryant, Vanessa L.; Okada, Satoshi; Ailal, Fatima; Bustamante, Jacinta; Casanova, Jean‐Laurent; Hirst, Jennifer; Boisson–Dupuis, Stéphanie

doi:10.1371/journal.pone.0058286

Cited by 35 publications

(36 citation statements)

References 48 publications

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“…A more pronounced defect was observed in the presence of high doses of IFN-γ. Haploinsufficiency at the human IFNGR2 locus was restricted to EBV-B cells and T lymphocytes, but was not observed in monocytes and monocyte-derived macrophages (MDMs) [152]. The clinical penetrance of AD IFN-γR2 deficiency is very low, as only one of 18 heterozygous individuals was found to be affected, and the treatment of symptomatic individuals is based entirely on curative antibiotic treatments.…”

Section: Ifn-γr2 Deficiencymentioning

confidence: 99%

Mendelian susceptibility to mycobacterial disease: Genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

Bustamante

Boisson–Dupuis

Abel

et al. 2014

Seminars in Immunology

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609

655

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Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity.

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Section: Ifn-γr2 Deficiencymentioning

confidence: 99%

Mendelian susceptibility to mycobacterial disease: Genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

Bustamante

Boisson–Dupuis

Abel

et al. 2014

Seminars in Immunology

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609

655

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“…Munc18-1 is encoded by the STXBP1 gene that is found to be mutated in cases with nonsyndromal ID and ID with epilepsy (Hamdan et al, 2011; Milh et al, 2011). Munc18-1 has been ascribed a variety of functions in exocytosis and has been shown to promote vesicle priming, SNARE complex assembly, trafficking of syntexin1 to the plasma membrane, by preventing the formation of ectopic SNARE complexes (Kong et al, 2013; Smyth et al, 2013; Zhou et al, 2013). …”

Section: Genes Linked To Id and Asdmentioning

confidence: 99%

“…Mutations in genes encoding AP4 complex subunits (AP4B1, AP4E1, and AP4S1) have been identified in patients with ID, progressive spastic paraplegia, shy character, and short stature (Abou Jamra et al, 2011). Mutations in AP4M1 and AP4E1 have recently been found in patients with cerebral palsy associated with severe ID (Abou Jamra et al, 2011; Kong et al, 2013; Moreno-De-Luca et al, 2011)…”

Section: Genes Linked To Id and Asdmentioning

confidence: 99%

Intellectual disability and autism spectrum disorders: Causal genes and molecular mechanisms

Srivastava

Schwartz

2014

Neuroscience & Biobehavioral Reviews

189

153

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Intellectual disability (ID) and Autism Spectrum disorder (ASD) are the most common developmental disorders present in humans. Combined, they affect between 3-5% of the population. Additionally, they can be found together in the same individual thereby complicating treatment. The causative factors (genes, epigenetic and environmental) are quite varied and likely interact so as to further complicate the assessment of an individual patient. Nonetheless, much valuable information has been gained by identifying candidate genes for ID or ASD. Understanding the etiology of either ID or ASD is of utmost importance for families. It allows a determination of the risk of recurrence, the possibility of other comorbidity medical problems, the molecular and cellular nature of the pathobiology and hopefully potential therapeutic approaches.

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“…Robust sequencing of the complete coding region (exome) has the potential to be clinically relevant in genetic diagnosis as understanding of the functional consequences in sequence variation improves [13]. Currently exome sequencing is discovering inborn errors of immunity in children that confer severe and selective vulnerability to certain infectious diseases [14,15]. …”

Section: Body Of the Articlementioning

confidence: 99%

Proteomics in immunity and herpes simplex encephalitis

Diego¹,

Mulvey²,

Casanova³

et al. 2013

Expert Review of Proteomics

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The genetic theory of infectious diseases has proposed that susceptibility to life-threatening infectious diseases in childhood, occurring in the course of primary infection, results mostly from individually rare but collectively diverse single-gene variants. Recent evidence for an ever-expanding spectrum of genes involved in susceptibility to infectious disease indicates the paradigm has important implications for diagnosis and treatment. One such pathology is childhood herpes simplex encephalitis (HSE), which shows a pattern of rare, but diverse disease-disposing genetic variants. The present report shows how proteomics can help to understand susceptibility to childhood HSE and other viral infections, suggests proteomics may have a particularly important role to play, emphasizes that variation over the population is a critical issue for proteomics and notes some new challenges for proteomics and related bioinformatics tools in the context of rare, but diverse genetic defects.

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A Novel Homozygous p.R1105X Mutation of the AP4E1 Gene in Twins with Hereditary Spastic Paraplegia and Mycobacterial Disease

Cited by 35 publications

References 48 publications

Mendelian susceptibility to mycobacterial disease: Genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

Mendelian susceptibility to mycobacterial disease: Genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

Intellectual disability and autism spectrum disorders: Causal genes and molecular mechanisms

Proteomics in immunity and herpes simplex encephalitis

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