scholarly journals Novel Variations in the KDM5C Gene Causing X-Linked Intellectual Disability

2021 ◽  
Vol 8 (1) ◽  
pp. e646
Author(s):  
Po-Ming Wu ◽  
Wen-Hao Yu ◽  
Chi-Wu Chiang ◽  
Chen-Yu Wu ◽  
Jia-Shing Chen ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Autistic Spectrum Disorder ◽  
Molecular Genetic ◽  
Facial Dysmorphism ◽  
Chinese Families ◽  
C Terminus ◽  
Pathologic Features ◽  
Physical Examinations ◽  
Male Patients ◽  
Exome Sequence

Background and ObjectivesTo investigate the pathogenicity of 2 novel KDM5C variations, report the clinical and neuroimaging findings, and review the available literature.MethodsPhysical examinations, structural neuroimaging studies, and exome sequence analysis were performed. KDM5C constructs were used to study the effect of the variations in transfected cells.ResultsWe identified 2 novel variations c.2233C>G and c.3392_3393delAG in the KDM5C gene harboring from 2 Chinese families with X-linked intellectual disability (ID). The affected male patients exhibited severe ID, short stature, and facial dysmorphism. The 1 with c.3392_3393delAG additionally had epilepsy and autistic spectrum disorder (ASD). Transiently transfected mutant KDM5C constructs both reduced protein expression and stability and decreased histone demethylase activities in cells. Reviewing the available literature, we found that the associated ASD tended to occur in patients with variations near the C-terminus of KDM5C.DiscussionWe report the clinical, molecular genetic, and pathologic features in patients with novel variations of KDM5C. The variability of the clinical phenotype in addition to an ID may associate with altered particular parts of KDM5C.

scholarly journals First Report of a de novo 10q23.31q23.33 Microdeletion: Obesity, Intellectual Disability and Microcephaly

2021 ◽  
pp. 1-5
Author(s):  
Ayberk Turkyilmaz ◽  
Erdal Kurnaz ◽  
Atilla Cayir
Keyword(s):  
Intellectual Disability ◽  
Array Cgh ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Autism Spectrum ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Genetic And Environmental Factors

Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and understanding cause-effect relationships. Some cases have ID as the only finding and are called isolated cases. Conversely, cases accompanied by facial dysmorphism, microcephaly, autism spectrum disorder, epilepsy, obesity, and congenital anomalies are called syndromic developmental delay (DD)/ID. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Genetic etiology can be detected in approximately 40% of the cases, whereas chromosomal abnormalities are observed in 25%. Obesity is a multifactorial disease in which both genetic and environmental factors play important roles. The role of heredity in obesity has been reported to be between 40 and 70%. Array-based comparative genomic hybridization (array-CGH) can detect CNVs in the whole genome at a higher resolution than conventional cytogenetic methods. Array-CGH is currently recommended as the first-tier genetic test for ID cases worldwide. In the present study, we aimed to evaluate clinical, radiological, and genetic analyses of a 12-year and 4-month-old girl with microcephaly, ID, and obesity. In the array-CGH analysis, a 3.1-Mb deletion, arr[GRGh37] 10q23.31g23.33 (92745793_95937944)×1 was detected, and this alteration was evaluated to be pathogenic. We consider that haploinsufficiency of the candidate genes (<i>GPR120</i>, <i>KIF11</i>, <i>EXOC6</i>, <i>CYP26A1</i>, <i>CYP26C1</i>, and <i>LGI1</i>) in the deletion region may explain microcephaly, ID, obesity, seizures, and ophthalmological findings in our patient. The investigation of 10q23.31q23.33 microdeletion in cases with syndromic obesity may contribute to molecular genetic diagnosis.

scholarly journals Clonazepam as an Effective Treatment for Epilepsy in a Female Patient with NEXMIF Mutation: Case Report

2020 ◽  
Vol 11 (4) ◽  
pp. 232-238 ◽  
Author(s):  
Masashi Ogasawara ◽  
Eiji Nakagawa ◽  
Eri Takeshita ◽  
Kohei Hamanaka ◽  
Satoko Miyatake ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Female Patient ◽  
De Novo ◽  
Intractable Epilepsy ◽  
Good Choice ◽  
De Novo Mutation ◽  
Facial Dysmorphism ◽  
Mild Intellectual Disability ◽  
Female Patients ◽  
Male Patients

The <i>NEXMIF</i> (<i>KIAA2022</i>) gene is located in the X chromosome, and hemizygous mutations in <i>NEXMIF</i> cause X-linked intellectual disability in male patients. Female patients with heterozygous mutations in <i>NEXMIF</i> also show similar, but milder, intellectual disability. Most female patients demonstrate intractable epilepsy compared with male patients, and the treatment strategy for epilepsy is still uncertain. Thus far, 24 female patients with <i>NEXMIF</i> mutations have been reported. Of these 24 patients, 20 also have epilepsy. Until now, epilepsy has been controlled in only 2 of these female patients. We report a female patient with a heterozygous de novo mutation, NM_001008537.2:c.1123del (p.Glu375Argfs*21), in <i>NEXMIF</i>. The patient showed mild intellectual disability, facial dysmorphism, obesity, generalized tonic-clonic seizures, and nonconvulsive status epilepticus. Sodium valproate was effective but caused secondary amenorrhea. We successfully treated her epilepsy with clonazepam without side effects, indicating that clonazepam might be a good choice to treat epilepsy in patients with <i>NEXMIF</i> mutations.

Genetic testing for autistic spectrum disorders

2020 ◽  
pp. 78-79
Author(s):  
Е.А. Померанцева ◽  
А.А. Исаев ◽  
А.П. Есакова ◽  
И.В. Поволоцкая ◽  
Е.В. Денисенкова ◽  
...  
Keyword(s):  
Genetic Testing ◽  
American Academy ◽  
Autistic Spectrum Disorder ◽  
Genetic Factors ◽  
Molecular Genetic ◽  
Autistic Spectrum Disorders ◽  
Autistic Spectrum ◽  
American Academy Of Pediatrics ◽  
Spectrum Disorders ◽  
Testing Algorithm

Согласно рекомендациям Американской академии педиатрии при постановке диагноза аутизм, следует направить семью на консультацию генетика и генетическое обследование. Однако оптимальный подход к алгоритму генетического обследования при выявлении расстройства аутистического спектра еще предстоит разработать. В рамках исследования было проведено сравнение выявляемости генетических факторов аутизма различными молекулярно-генетическими тестами. According to American Academy of Pediatrics recent guidelines, each family with a child diagnosed with autistic spectrum disorder should be reffered to a medical geneticist and offered genetic tests. However, an optimal genetic testing algorithm has yet to be developed. This study was conducted to compare abilities of different molecular-genetic methods to detect genetic factors of autistic spectrum disorders.

scholarly journals Pitt–Hopkins syndrome with electrical stat us epileptic us in slo w-wave sleep: a case report

2019 ◽  
Vol 14 (2) ◽  
pp. 42-48
Author(s):  
N. G. Lyukshina
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Status Epilepticus ◽  
Neuronal Differentiation ◽  
Clinical Case ◽  
Genetic Disorder ◽  
Facial Dysmorphism ◽  
Autistic Behavior ◽  
Rare Genetic Disorder ◽  
Molecular Variant

Pitt–Hoppkins syndrome is rare genetic disorder caused by a molecular variant of TCF4 which is involved in embryologic neuronal differentiation. The syndrome is characterized by specific facial dysmorphism, phychomotor delay, autistic behavior and intellectual disability. Other associated features include ealy-onset myopia, seizures, constipation and hyperventilation-apneic spells. We introduced a clinical case of the patient with molecularly confirmed TCF4 variant and previously undescribed combination with syndrome of the electrical status epilepticus during sleep.

scholarly journals Association of the I/D polymorphism of angiotensinconverting enzyme gene with the development of essential hypertension

2019 ◽  
Vol 34 (3) ◽  
pp. 87-96
Author(s):  
O. S. Pavlova ◽  
S. E. Ogurtsova ◽  
M. M. Liventseva ◽  
T. H. Lakotko ◽  
I. Y. Korobko ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Molecular Genetic ◽  
Recessive Model ◽  
Control Group ◽  
Molecular Genetic Study ◽  
Ace Gene ◽  
Paternal Line ◽  
Male Patients ◽  
Polymerase Chain ◽  
The Impact

Objective. To determine the impact of the I/D polymorphism of the angiotensin-converting enzyme (ACE) gene on the development of essential hypertension, taking into account gender differences.Material and Methods. Clinical data were assessed and a molecular genetic study was performed in 602 people including 401 patients with essential hypertension and 201 individuals of the control group, representing the Belarusian ethnic group. Genotyping was performed using the method of polymerase chain reaction and restriction fragment length polymorphism.Results. The distribution of genotypes of the I/D polymorphism of the ACE gene did not differ between patients with hypertension and normotensive individuals: II, ID, and DD genotypes were detected in 100 (24.9%), 192 (47.9%), and 109 (27.2%) patients and in 52 (25.9%), 108 (53.7%), and 41 (20.4%) people of the comparison group, respectively. Differences were found between the distribution of DD genotype in men with hypertension and in the control group, where the frequencies were 28.4% and 17.3% (p  =  0.04), respectively, in contrast to no differences in women: 25.8% and 23.3% (p  =  0.64), respectively. Carrying the DD genotype in men compared with the ID and DD genotypes (recessive model) of the I/D polymorphism of the ACE gene increased the probability of developing essential hypertension by 1.9 times (OR   =   1.89; 95% CI  =  1.04-3.44). The analysis of the prevalence of risk factors depending on the I/D polymorphism of the ACE gene showed that male patients with the DD genotype more often had burdened heredity in regard to the development of premature cardiovascular diseases (23 patients (37.7%)) compared with the individuals with II and ID genotypes: 13 (21.7%) and 14 (14.9%) patients, respectively (χ2  =  1.16; p  =   0.005), and mainly through the paternal line.Conclusions. Development of essential hypertension is associated with the carriership of the mutant DD genotype of I/D polymorphism of the ACE gene in men. 

scholarly journals MED13L-related intellectual disability due to paternal germinal mosaicism

2021 ◽  
pp. mcs.a006124
Author(s):  
Beata Bessenyei ◽  
Istvan Balogh ◽  
Attila Mokanszki ◽  
Aniko Ujfalusi ◽  
Rolph Pfundt ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Mediator Complex ◽  
Facial Dysmorphism ◽  
Facial Features ◽  
Speech Delay ◽  
Motor Delay ◽  
First Case ◽  
Intragenic Deletion ◽  
Germinal Mosaicism

The MED13L-related intellectual disability or MRFACD syndrome (Mental retardation and distinctive facial features with or without cardiac defects; MIM # 616789) is one of the most common form of syndromic intellectual disability with about a hundred cases reported so far. Affected individuals share overlapping features comprising intellectual disability, hypotonia, motor delay, remarkable speech delay, and a recognizable facial gestalt. De novo disruption of the MED13L gene by deletions, duplications or sequence variants has been identified deleterious. Siblings affected by intragenic deletion transmitted from a mosaic parent have been reported once in the literature. We now present the first case of paternal germinal mosaicism for a missense MED13L variant causing MRFACD syndrome in one of the father's children and be the likely cause of intellectual disability and facial dysmorphism in the other. As part of the Mediator complex, the MED proteins have an essential role in regulating transcription. 32 subunits of the Mediator complex genes have been linked to congenital malformations that are now acknowledged as transcriptomopathies. The MRFACD syndrome has been suggested to represent a recognizable phenotype.

scholarly journals Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Nekane Ibarluzea ◽  
Ana Belén de la Hoz ◽  
Olatz Villate ◽  
Isabel Llano ◽  
Intzane Ocio ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Next Generation Sequencing ◽  
Fragile X ◽  
Next Generation ◽  
Sequencing Data ◽  
Targeted Next Generation Sequencing ◽  
Biochemical Assays ◽  
History Of ◽  
Male Patients ◽  
Generation Sequencing

X-linked intellectual disability (XLID) is known to contribute up to 10% of intellectual disability (ID) in males and could explain the increased ratio of affected males observed in patients with ID. Over the past decade, next-generation sequencing has clearly stimulated the gene discovery process and has become part of the diagnostic procedure. We have performed targeted next-generation sequencing of 82 XLID genes on 61 non-related male patients with suggestive non-syndromic XLID. These patients were initially referred to the molecular genetics laboratory to exclude Fragile X Syndrome. The cohort includes 47 male patients with suggestive X-linked family history of ID meaning that they had half-brothers or maternal cousins or uncles affected; and 14 male patients with ID and affected brothers whose mothers show skewed X-inactivation. Sequencing data analysis identified 17 candidate variants in 16 patients. Seven families could be re-contacted and variant segregation analysis of the respective eight candidate variants was performed: HUWE1, IQSEC2, MAOA, MED12, PHF8, SLC6A8, SLC9A6, and SYN1. Our results show the utility of targeted next-generation sequencing in unravelling the genetic origin of XLID, especially in retrospective cases. Variant segregation and additional studies like RNA sequencing and biochemical assays also helped in re-evaluating and further classifying the genetic variants found.

Focal myositis

Neurology ◽  
2018 ◽  
Vol 90 (12) ◽  
pp. e1013-e1020 ◽  
Author(s):  
Laure Gallay ◽  
Arnaud Hot ◽  
Philippe Petiot ◽  
Françoise Thivolet-Bejui ◽  
Delphine Maucort-Boulch ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Cohort Study ◽  
Inflammatory Disease ◽  
Immunosuppressive Drugs ◽  
Serum Creatine Kinase ◽  
Immune Mediated ◽  
Pathologic Features ◽  
Antibody Positivity ◽  
Male Patients ◽  
Inflammatory Syndrome

ObjectiveTo better define in a cohort study the clinical and pathologic features of focal myositis (FM).MethodsWith the use of the usual clinicopathologic definition, each confirmed case of FM in the Lyon University Hospital's myopathologic database between 2000 and 2016 was retrieved. Clinical, pathologic, imaging, serologic, and therapeutic data were collected. When data were missing but feasible, appropriate pathologic analyses were performed.ResultsOf the 924 patients included in the database, 37 (4%) had confirmed FM (14 female, 23 male patients). The main symptoms were pain (n = 30, 81%), muscular mass (n = 16, 43%), erythema at the site of FM (n = 12, 32%), and fever (n = 9, 24%). Serum creatine kinase was normal in most patients (81%); serum immune abnormalities were frequent (inflammatory syndrome in sera [39%], dysglobulinemia [52%], and anti-nuclear antibody positivity [29%]). In addition to confirming previously reported findings, pathologic analyses found significant rates of vasculitis (68%) and fasciitis (73%). Here, FM appeared frequently to be associated with other diseases such as immune-mediated inflammatory disease (IMID; 32%), neoplasia (24%), and radiculopathy (11%). Regarding outcomes, 64% of the cases had received immunosuppressive drugs, and the relapse rate was 41%.ConclusionThe present study suggests that FM is not as innocuous as previously believed, particularly considering the associated disorders. Notably, patients with FM should receive careful IMID and neoplasia screening.

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