scholarly journals A de novo variant in the X‐linked gene CNKSR2 is associated with seizures and mild intellectual disability in a female patient

2019 ◽  
Vol 7 (10) ◽  
Author(s):  
Daniel L. Polla ◽  
Harriet R. Saunders ◽  
Bert B. A. Vries ◽  
Hans Bokhoven ◽  
Arjan P. M. Brouwer
Keyword(s):  
Intellectual Disability ◽  
Female Patient ◽  
De Novo ◽  
Mild Intellectual Disability ◽  
Linked Gene ◽  
De Novo Variant

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.

scholarly journals A de novo variant in CASK gene causing intellectual disability and brain hypoplasia: A Case Report and Literature Review

2021 ◽  
Author(s):  
Ying Zhang ◽  
Yanyan Nie ◽  
Yu Mu ◽  
Jie Zheng ◽  
Xiaowei Xu ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mental Disorders ◽  
De Novo ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Loss Of Function ◽  
Bioinformatics Analyses ◽  
Whole Exome ◽  
De Novo Variant

Abstract Background：The pathogenic variation of CASK gene can cause CASK related mental disorders. The main clinical manifestations are microcephaly with pontine and cerebellar hypoplasia, X-linked mental disorders with or without nystagmus and FG syndrome. The main pathogenic mechanism is the loss of function of related protein caused by mutation. We reported a Chinese male newborn with a de novo variant in CASK gene. Case presentation：We present an 18-day-old baby with intellectual disability and brain hypoplasia. Whole-exome sequencing was performed, which detected a hemizygous missense mutation c.764G>A of CASK gene. The mutation changed the 255th amino acid from Arg to His. Software based bioinformatics analyses were conducted to infer its functional effect.Conclusions：In this paper, a de novo mutation of CASK gene was reported. Moreover, a detailed description of all the cases described in the literature is reported.CASK mutations cause a variety of clinical phenotypes. Its diagnosis is difficult due to the lack of typical clinical symptoms. Genetic testing should be performed as early as possible if this disease is suspected. This case provides an important reference for the diagnosis and treatment of future cases.

scholarly journals Focal segmental glomerulosclerosis and mild intellectual disability in a patient with a novel de novo truncating TRIM8 mutation

2020 ◽  
Vol 63 (9) ◽  
pp. 103972
Author(s):  
Martin A. McClatchey ◽  
Zachary D. du Toit ◽  
Rhys Vaughan ◽  
Sharon D. Whatley ◽  
Sara Martins ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Focal Segmental Glomerulosclerosis ◽  
De Novo ◽  
Mild Intellectual Disability ◽  
Segmental Glomerulosclerosis

scholarly journals Case Report: CNNM2 Mutations Cause Damaged Brain Development and Intractable Epilepsy in a Patient Without Hypomagnesemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiucui Li ◽  
Shijia Bao ◽  
Wei Wang ◽  
Xulai Shi ◽  
Ying Hu ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Brain Development ◽  
De Novo ◽  
Basolateral Membrane ◽  
Intractable Epilepsy ◽  
Chinese Patient ◽  
Renal Tubules ◽  
Variable Degree ◽  
Mild Intellectual Disability ◽  
Severity Of The Disease

A series of neurological manifestations such as intellectual disability and epilepsy are closely related to hypomagnesemia. Cyclin M2 (CNNM2) proteins, as a member of magnesium (Mg2+) transporters, were found along the basolateral membrane of distal renal tubules and involved in the reabsorption of Mg2+. Homozygous and heterozygous variants in CNNM2 reported so far were responsible for a variable degree of hypomagnesemia, several of which also showed varying degrees of neurological phenotypes such as intellectual disability and epilepsy. Here, we report a de novo heterozygous CNNM2 variant (c.2228C &gt; T, p.Ser743Phe) in a Chinese patient, which is the variant located in the cyclic nucleotide monophosphate-binding homology (CNBH) domain of CNNM2 proteins. The patient presented with mild intellectual disability and refractory epilepsy but without hypomagnesemia. Thus, we reviewed the literature and analyzed the phenotypes related to CNNM2 variants, and then concluded that the number of variant alleles and the changed protein domains correlates with the severity of the disease, and speculated that the CNBH domain of CNNM2 possibly plays a limited role in Mg2+ transport but a significant role in brain development. Furthermore, it can be speculated that neurological phenotypes such as intellectual disability and seizures can be purely caused by CNNM2 variants.

A novel de novo heterozygous deletion at 13q14.2-q21.1 in two siblings with mild intellectual disability

Gene Reports ◽  
2018 ◽  
Vol 12 ◽  
pp. 201-207
Author(s):  
Kirti Mittal ◽  
Laxmi Kirola ◽  
Sridevi Hegde ◽  
Mitesh Shetty ◽  
Madhulika Kabra ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Heterozygous Deletion ◽  
Mild Intellectual Disability

scholarly journals A 9-year-old-girl with Phelan McDermid Syndrome, who had been diagnosed with an autism spectrum disorder

2016 ◽  
Vol 19 (2) ◽  
pp. 85-90 ◽  
Author(s):  
I Görker ◽  
H Gürkan ◽  
S Demir Ulusal ◽  
E Atlı ◽  
E Ikbal Atlı
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Comparative Genomic ◽  
Parental Origin ◽  
Mild Intellectual Disability ◽  
First Case

AbstractPhelan McDermid Syndrome (PHMDS) (OMIM #606232), is a contiguous gene disorder resulting from deletion of the distal long arm of chromosome 22. The 22q13.3 deletions and mutations that lead to a loss of a functional copy of SHANK3 (OMIM *606230) cause the syndrome, characterized by moderate to profound intellectual disability, severely delayed or absent speech, hypotonia, and autism spectrum disorder (ASD) or ASD traits. In this study, we present the case of a 9-year-old girl who had earlier been diagnosed with an ASD. Our findings were a clinically mild intellectual disability, rounded face, pointed chin but no autistic findings. We learned that her neuromotor development was delayed and she had neonatal hypotonia in her history. A heterozygous deletion of MLC1, SBF1, MAPK8IP2, ARSA, SHANK3 and ACR genes, located on 22q13.33, was defined by multiplex ligation-dependent probe amplification (MLPA). Deletion of 22q13.3 (ARSA) region was confirmed by a fluorescent in situ hybridization (FISH) technique. The 22q13.3 deletion was found to be de novo in our patient, and she was diagnosed with PHMDS. We confirmed the 22q13.3 deletion and also determined a gain of 8p23.3-23.2 by array comparative genomic hybridization (aCGH). Fluorescent in situ hybridization was performed to determine whether the deletion was of parental origin and to identify regions of chromosomes where the extra 8p may have been located. The parents were found to be normal. The extra copy of 8p was observed on 22q in the patient. She is the first case reported in association with the 22q deletion of 8p duplications in the literature.

A de novo 3.57 Mb microdeletion in 8q12.3q13.2 in a patient with mild intellectual disability and epilepsy

2012 ◽  
Vol 55 (5) ◽  
pp. 358-361 ◽  
Author(s):  
Willem M.A. Verhoeven ◽  
Jos I.M. Egger ◽  
Ilse Feenstra ◽  
Nicole de Leeuw
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Mild Intellectual Disability

scholarly journals A Rare, Recurrent,De Novo14q32.2q32.31 Microdeletion of 1.1 Mb in a 20-Year-Old Female Patient with a Maternal UPD(14)-Like Phenotype and Intellectual Disability

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Almira Zada ◽  
Farmaditya E. P. Mundhofir ◽  
Rolph Pfundt ◽  
Nico Leijsten ◽  
Willy Nillesen ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Female Patient ◽  
De Novo ◽  
Fragile X ◽  
Genetic Diagnosis ◽  
Facial Dysmorphism ◽  
Feeding Problems ◽  
Motor Delay ◽  
Genome Wide ◽  
Low Copy Repeats

We present a 20-year-old female patient from Indonesia with intellectual disability (ID), proportionate short stature, motor delay, feeding problems, microcephaly, facial dysmorphism, and precocious puberty who was previously screened normal for conventional karyotyping, fragile X testing, and subtelomeric MLPA analysis. Subsequent genome wide array analysis was performed on DNA from blood and revealed a 1.1 Mb deletion in 14q32.2q32.31 (chr14:100,388,343-101,506,214; hg19). Subsequent carrier testing in the parents by array showed that the deletion had occurredde novoin the patient and that her paternal 14q32 allele was deleted. The deleted region encompasses theDLK1/GTL2imprinted gene cluster which is consistent with the maternal UPD(14)-like phenotype of the patient. This rare, recurrent microdeletion was recently shown not to be mediated by low copy repeats, but by expanded TGG repeats, flanking the 14q32.2q32.21 deletion boundaries, a novel mechanism of recurrent genomic rearrangement. This is another example how the application of high resolution genome wide testing provides an accurate genetic diagnosis, thereby improving the care for patients and optimizing the counselling for family.

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