scholarly journals Genetic Defects Underlie the Non-syndromic Autosomal Recessive Intellectual Disability (NS-ARID)

2017 ◽  
Vol 12 (1) ◽  
pp. 167-177
Author(s):  
Shamim Saleha ◽  
Muhammad Sajid ◽  
Shaista Zafar ◽  
Neelam Pervaiz
Keyword(s):  
Intellectual Disability ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Neurodevelopmental Disorder ◽  
Molecular Genetic ◽  
Family Health ◽  
Genetic Mutations ◽  
Genetic Defects ◽  
Genetic Etiology ◽  
Genetic Techniques

AbstractIntellectual disability (ID) is a neurodevelopmental disorder which appears frequently as the result of genetic mutations and may be syndromic (S-ID) or non-syndromic (NS-ID). ID causes an important economic burden, for patient's family, health systems, and society. Identifying genes that cause S-ID can easily be evaluated due to the clinical symptoms or physical anomalies. However, in the case of NS-ID due to the absence of co-morbid features, the latest molecular genetic techniques can be used to understand the genetic defects that underlie it. Recent studies have shown that non-syndromic autosomal recessive (NS-ARID) is extremely heterogeneous and contributes much more than X-linked ID. However, very little is known about the genes and loci involved in NS-ARID relative to X-linked ID, and whose complete genetic etiology remains obscure. In this review article, the known genetic etiology of NS-ARID and possible relationships between genes and the associated molecular pathways of their encoded proteins has been reviewed which will enhance our understanding about the underlying genes and mechanisms in NS-ARID.

scholarly journals Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder

2021 ◽  
Author(s):  
Francesca Mattioli ◽  
Hossein Darvish ◽  
Sohail Aziz Paracha ◽  
Abbas Tafakhori ◽  
Saghar Ghasemi Firouzabadi ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mouse Model ◽  
Autosomal Recessive ◽  
High Throughput Sequencing ◽  
Neurodevelopmental Disorder ◽  
Behavioral Changes ◽  
Causative Role ◽  
Speech Impairment ◽  
Lipid Flippase

Intellectual disability (ID) is a highly heterogeneous disorder with hundreds of associated genes. Despite progress in the identification of the genetic causes of ID following the introduction of high-throughput sequencing, about half of affected individuals still remain without a molecular diagnosis. Consanguineous families with affected individuals provide a unique opportunity to identify novel recessive causative genes. In this report we describe a novel autosomal recessive neurodevelopmental disorder. We identified two consanguineous families with homozygous variants predicted to alter the splicing of ATP9A which encodes a transmembrane lipid flippase of the class II P4-ATPases. The three individuals homozygous for these putatively truncating variants presented with severe ID, motor and speech impairment, and behavioral anomalies. Consistent with a causative role of ATP9A in these patients, a previously described Atp9a-/- mouse model showed behavioral changes.

scholarly journals Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features

2021 ◽  
Author(s):  
Maha S. Zaki ◽  
Andrea Accogli ◽  
Ghayda Mirzaa ◽  
Fatima Rahman ◽  
Hiba Mohammed ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Autosomal Recessive ◽  
Neurodevelopmental Disorder ◽  
Death Domain ◽  
Multiprotein Complex ◽  
Related Disorder ◽  
Pathogenic Variants ◽  
Domain Protein ◽  
Caspase 2 ◽  
And Behavior

AbstractThe PIDDosome is a multiprotein complex, composed by the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 that induces apoptosis in response to DNA damage. In the recent years, biallelic pathogenic variants in CRADD have been associated with a neurodevelopmental disorder (MRT34; MIM 614499) characterized by pachygyria with a predominant anterior gradient, megalencephaly, epilepsy and intellectual disability. More recently, biallelic pathogenic variants in PIDD1 have been described in a few families with apparently nonsydnromic intellectual disability. Here, we aim to delineate the genetic and radio-clinical features of PIDD1-related disorder. Exome sequencing was carried out in six consanguineous families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals as well as reviewing all the data from previously reported cases. We identified five distinct novel homozygous variants (c.2584C>T p.(Arg862Trp), c.1340G>A p.(Trp447*), c.2116_2120del p.(Val706Hisfs*30), c.1564_1565delCA p.(Gln522fs*44), and c.1804_1805del p.(Gly602fs*26) in eleven subjects displaying intellectual disability, behaviorial and psychiatric features, and a typical anterior-predominant pachygyria, remarkably resembling the CRADD-related neuroimaging pattern. In summary, we outline the phenotypic and molecular spectrum of PIDD1 biallelic variants supporting the evidence that the PIDD1/CRADD/caspase-2 signaling is crucial for normal gyration of the developing human neocortex as well as cognition and behavior.

Autosomal Recessive Primary Microcephaly (MCPH): An Update

2017 ◽  
Vol 48 (03) ◽  
pp. 135-142 ◽  
Author(s):  
Deborah Morris-Rosendahl ◽  
Angela Kaindl ◽  
Sami Zaqout
Keyword(s):  
Intellectual Disability ◽  
Head Circumference ◽  
Autosomal Recessive ◽  
Neurodevelopmental Disorder ◽  
Speech Disorder ◽  
Rare Disorder ◽  
Primary Microcephaly ◽  
Expressive Speech ◽  
Autosomal Recessive Primary Microcephaly

AbstractAutosomal recessive primary microcephaly (MCPH; MicroCephaly Primary Hereditary) is a genetically heterogeneous neurodevelopmental disorder characterized by a significantly reduced head circumference present already at birth and intellectual disability. Inconsistent features include hyperactivity, an expressive speech disorder, and epilepsy. Here, we provide a brief overview on this rare disorder pertinent for clinicians.

Muscular dystrophies and other genetic myopathies

2018 ◽  
Author(s):  
Stefen Brady ◽  
David Hilton-Jones
Keyword(s):  
Molecular Genetic ◽  
Immunosuppressive Treatment ◽  
Clinical History ◽  
Muscular Dystrophies ◽  
Genetic Mutations ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Diagnostic Confusion ◽  
Genetic Techniques ◽  
Diagnostic Investigations

Muscular dystrophies are a genetically and phenotypically heterogeneous group of progressive muscle diseases. Modern molecular genetic techniques have made it possible to clarify the genetic mutations responsible for most muscular dystrophies. Despite advances in genetics, the importance of the clinical history and physical examination has increased rather than diminished. It is only through correctly identifying the clinical features that the appropriate diagnostic investigations will be performed. Although muscular dystrophies are typically slowly progressive disorders in which muscle atrophy and weakness are the defining characteristics, diagnostic confusion with the idiopathic inflammatory myopathies (IIM) can occur, and a diagnosis of muscular dystrophy may be considered only after the failure of immunosuppressive treatment for a presumed case of IIM. This chapter reviews the various muscular dystrophies, and discusses how to differentiate between them and the IIM.

scholarly journals Biallelic truncation variants in ATP9A are associated with a novel autosomal recessive neurodevelopmental disorder

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Francesca Mattioli ◽  
Hossein Darvish ◽  
Sohail Aziz Paracha ◽  
Abbas Tafakhori ◽  
Saghar Ghasemi Firouzabadi ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mouse Model ◽  
Autosomal Recessive ◽  
High Throughput Sequencing ◽  
Neurodevelopmental Disorder ◽  
Behavioral Changes ◽  
Causative Role ◽  
Speech Impairment ◽  
Lipid Flippase

AbstractIntellectual disability (ID) is a highly heterogeneous disorder with hundreds of associated genes. Despite progress in the identification of the genetic causes of ID following the introduction of high-throughput sequencing, about half of affected individuals still remain without a molecular diagnosis. Consanguineous families with affected individuals provide a unique opportunity to identify novel recessive causative genes. In this report, we describe a novel autosomal recessive neurodevelopmental disorder. We identified two consanguineous families with homozygous variants predicted to alter the splicing of ATP9A which encodes a transmembrane lipid flippase of the class II P4-ATPases. The three individuals homozygous for these putatively truncating variants presented with severe ID, motor and speech impairment, and behavioral anomalies. Consistent with a causative role of ATP9A in these patients, a previously described Atp9a−/− mouse model showed behavioral changes.

scholarly journals The utility of molecular genetic techniques in craniosynostosis cases associated with intellectual disability

2018 ◽  
Vol 26 (4) ◽  
pp. 471-477
Author(s):  
Alina Bogliş ◽  
Florin Tripon ◽  
Claudia Bănescu
Keyword(s):  
Intellectual Disability ◽  
Sanger Sequencing ◽  
Genetic Disorder ◽  
Molecular Genetic ◽  
Diagnostic Testing ◽  
Pathogenic Mutation ◽  
Mild Intellectual Disability ◽  
Fibroblast Growth Factor Receptors ◽  
Fgfr3 Gene ◽  
Genetic Techniques

Abstract Molecular genetic testing in craniosynostosis leads to the detection of the mutations in the genes encoding fibroblast growth factor receptors (FGFR), providing information about the etiology of the genetic disorder. Muenke syndrome is produced by p.Pro250Arg mutation in FGFR3 gene with evidence of variable expressivity, representing 8% of the syndromic craniosynostoses. Here, we present the identification of a p.Pro250Arg pathogenic mutation (c.749C>G) in the FGFR3 gene using Multiplex Ligation-dependent Probes Amplification (MLPA) analysis in conjunction with Sanger sequencing in a patient with craniosynostosis and mild intellectual disability. The MLPA analysis detected a reduced signal of the probe, at the site of the c.749C>G mutation, defined by the presence of one allele of C749>G mutation in the FGFR3 gene, exon 7. Sanger sequencing was performed for confirmation and identified heterozygous p.Pro250Arg pathogenic variant (c.749C>G) in exon 7 of the FGFR3. In conclusion, we assessed the validity and clinical utility of the combined molecular genetic techniques, MLPA analysis, and Sanger sequencing, for craniosynostosis and intellectual disability, improving not only the diagnostic testing but also the genetic counseling and management of the disorder.

scholarly journals Pyridoxine-Dependent Epilepsy and Antiquitin Deficiency Resulting in Neonatal-Onset Refractory Seizures

2021 ◽  
Vol 12 (1) ◽  
pp. 65
Author(s):  
Konrad Kaminiów ◽  
Magdalena Pająk ◽  
Renata Pająk ◽  
Justyna Paprocka
Keyword(s):  
Intellectual Disability ◽  
Vitamin B6 ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Neonatal Seizures ◽  
Semialdehyde Dehydrogenase ◽  
Phenotypic Spectrum ◽  
Neonatal Onset ◽  
Toxic Metabolites ◽  
Refractory Seizures

Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive neurometabolic disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase (mutation in ALDH7A1 gene), more commonly known as antiquitin (ATQ). ATQ is one of the enzymes involved in lysine oxidation; thus, its deficiency leads to the accumulation of toxic metabolites in body fluids. PDE is characterized by persistent, recurrent neonatal seizures that cannot be well controlled by antiepileptic drugs but are responsive clinically and electrographically to daily pyridoxine (vitamin B6) supplementation. Although the phenotypic spectrum distinguishes between typical and atypical, pyridoxine-dependent is true for each. Diagnosis may pose a challenge mainly due to the rarity of the disorder and the fact that seizures may not occur until childhood or even late adolescence. Moreover, patients may not demonstrate an obvious clinical or electroencephalography response to the initial dose of pyridoxine. Effective treatment requires lifelong pharmacologic supplements of pyridoxine, and dietary lysine restriction and arginine enrichment should improve prognosis and avoid developmental delay and intellectual disability. The purpose of this review is to summarize briefly the latest reports on the etiology, clinical symptoms, diagnosis, and management of patients suffering from pyridoxine-dependent epilepsy.

Papillon-Lefevre Syndrome: Challenge for Periodontal Management

2019 ◽  
Vol 3 (2) ◽  
pp. 84-86
Author(s):  
Krishna Prasad Lamichhane ◽  
Shaili Pradhan ◽  
Ranjita Shreshta Gorkhali ◽  
Pramod Kumar Koirala
Keyword(s):  
Significant Role ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutations ◽  
Rare Autosomal Recessive Disorder ◽  
Diagnosis And Management ◽  
Periodontal Destruction ◽  
Palmoplantar Keratosis

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder associated with rapidly progressing periodontitis leading to premature loss of deciduous and permanent dentition and diffuse palmoplantar keratosis. Immunologic alterations, genetic mutations, and role of bacteria are some aetiologic factors. Patients present with early periodontal destruction, so periodontists play a significant role in diagnosis and management. This paper reports a case of Papillon- Lefevre syndrome with its clinical manifestations and challenges for periodontal management which was diagnosed in dental department.

Biallelic variants in TMEM222 cause a new autosomal recessive neurodevelopmental disorder

2021 ◽  
Author(s):  
Daniel L. Polla ◽  
Mohammad Ali Farazi Fard ◽  
Zahra Tabatabaei ◽  
Parham Habibzadeh ◽  
Olga A. Levchenko ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Neurodevelopmental Disorder

scholarly journals Clinical and genetic spectrum of glycogen storage disease in Iranian population using targeted gene sequencing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zahra Beyzaei ◽  
Fatih Ezgu ◽  
Bita Geramizadeh ◽  
Mohammad Hadi Imanieh ◽  
Mahmood Haghighat ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Molecular Genetic ◽  
Gene Sequencing ◽  
Glycogen Storage ◽  
Loss Of Function ◽  
Retrospective Case ◽  
Complex Disorders ◽  
Glycogen Storage Diseases ◽  
Targeted Gene Sequencing ◽  
Retrospective Case Study

AbstractGlycogen storage diseases (GSDs) are known as complex disorders with overlapping manifestations. These features also preclude a specific clinical diagnosis, requiring more accurate paraclinical tests. To evaluate the patients with particular diagnosis features characterizing GSD, an observational retrospective case study was designed by performing a targeted gene sequencing (TGS) for accurate subtyping. A total of the 15 pediatric patients were admitted to our hospital and referred for molecular genetic testing using TGS. Eight genes namely SLC37A4, AGL, GBE1, PYGL, PHKB, PGAM2, and PRKAG2 were detected to be responsible for the onset of the clinical symptoms. A total number of 15 variants were identified i.e. mostly loss-of-function (LoF) variants, of which 10 variants were novel. Finally, diagnosis of GSD types Ib, III, IV, VI, IXb, IXc, X, and GSD of the heart, lethal congenital was made in 13 out of the 14 patients. Notably, GSD-IX and GSD of the heart-lethal congenital (i.e. PRKAG2 deficiency) patients have been reported in Iran for the first time which shown the development of liver cirrhosis with novel variants. These results showed that TGS, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate and high-throughput results for diagnosing and sub-typing GSD and related diseases.

Sign in / Sign up

Export Citation Format

Share Document