Novel homozygous mutation inKPTNgene causing a familial intellectual disability-macrocephaly syndrome

2015 ◽  
Vol 167 (8) ◽  
pp. 1913-1915 ◽  
Author(s):  
Sander Pajusalu ◽  
Tiia Reimand ◽  
Katrin Õunap
Keyword(s):  
Intellectual Disability ◽  
Homozygous Mutation

scholarly journals Identification of a Novel Nonsense Homozygous Mutation of LINS1 Gene in Two Sisters With Moderate Intellectual Disability, Schizophrenia, and Anxiety Disorders and Review of the Literature

2020 ◽  
Author(s):  
Chia-Hsiang Chen ◽  
Yu-Shu Huang ◽  
Ting-Hsuan Fang
Keyword(s):  
Intellectual Disability ◽  
Amino Acid ◽  
Stop Codon ◽  
Homozygous Mutation ◽  
Nucleotide Position ◽  
Sequencing Analysis ◽  
Moderate Intellectual Disability ◽  
Recessive Form ◽  
Cdna Nucleotide ◽  
Homozygous Nonsense Mutation

Abstract Background: The human LINS1 gene is located at 15q26.3 and encodes the lines homolog 1 protein that contains the Drosophila lines homologous domain. Mutations in the LINS1 gene have been reported to cause a rare recessive form of intellectual disability. A total of seven mutations in six studies have been reported in the literature to our knowledge. Results: Using whole genome sequencing analysis, we identified a novel homozygous nonsense mutation in the LINS1 gene in these two sisters who presented moderate intellectual disability, schizophrenia symptoms, and severe anxiety. The mutation was a C-to-T substitution at the cDNA nucleotide position 274 that changed the amino acid glutamine at the codon 92 to stop codon (Gln92X), resulting in the truncation of LINS1 protein after amino acid 91. This mutation was transmitted from their unrelated parents who were heterozygous carriers. Conclusions: Our findings not only add to the allelic heterogeneity of the LINS1-associated intellectual disability but also expand the spectrum of clinical phenotypes of patients with LINS1 mutations. Our study suggests that the human LINS1 gene mutation may play a role in the pathogenesis of psychosis and anxiety in addition to the intellectual disability.

A homozygous mutation in CMAS causes autosomal recessive intellectual disability in a Kazakh family

2019 ◽  
Vol 84 (1) ◽  
pp. 46-53 ◽  
Author(s):  
Ronggui Qu ◽  
Qing Sang ◽  
Xueqian Wang ◽  
Yao Xu ◽  
Biaobang Chen ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Autosomal Recessive ◽  
Homozygous Mutation

A Novel Frameshift Mutation in Abnormal Spindle-Like Microcephaly (ASPM) Gene in an Iranian Patient with Primary Microcephaly: A Case Report

2020 ◽  
Author(s):  
Afsaneh BAZGIR ◽  
Mehdi AGHA GHOLIZADEH ◽  
Faezeh SARVAR ◽  
Zahra PAKZAD
Keyword(s):  
Intellectual Disability ◽  
Frameshift Mutation ◽  
Genetic Disorder ◽  
Normal Function ◽  
Molecular Testing ◽  
Homozygous Mutation ◽  
Primary Microcephaly ◽  
Iranian Patient ◽  
Whole Exome ◽  
Autosomal Recessive Primary Microcephaly

Autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder, leading to the defect of neurogenic brain development. Individuals with MCPH reveal reduced head circumference and intellectual disability. Several MCPH loci have been identified from several populations. Genetic heterogeneity of this disorder represents molecular testing challenge. An 8 yr old female, born from consanguineous parents, was attended to Fardis Central Lab, Alborz, Iran. Based on the reduced circumference and intellectual disability, MCPH was diagnosed. Whole exome sequencing of the patient identified a novel homozygous frameshift mutation (c.2738dupT, p.Cys914fs) in exon 9 Abnormal Spindle-like Microcephaly )ASPM( gene. By Sanger sequencing, segregation analysis showed that both parents were heterozygous carriers for this variant. The novel frameshift mutation likely truncates the protein, resulting in loss of normal function ASPM in homozygous mutation carriers. The study might add a new pathogenic variant in mutations of the ASPM gene as a causative variant in patients with MCPH and might be helpful in genetic counseling of consanguineous families.

scholarly journals tRNA methyltransferase 10 homologue A (TRMT10A) mutation in a Chinese patient with diabetes, insulin resistance, intellectual deficiency and microcephaly

2020 ◽  
Vol 8 (1) ◽  
pp. e001601 ◽  
Author(s):  
Hu Lin ◽  
Xuelian Zhou ◽  
Xuefeng Chen ◽  
Ke Huang ◽  
Wei Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Intellectual Disability ◽  
Current Knowledge ◽  
Genetic Diagnosis ◽  
Insulin Dependent Diabetes ◽  
Homozygous Mutation ◽  
Intellectual Deficiency ◽  
Loss Of Function ◽  
Trna Methyltransferase ◽  
Insulin Dependent

IntroductionLoss-of-function mutations in tRNA methyltransferase 10 homologue A (TRMT10A), a tRNA methyltransferase, have recently been described as a monogenic cause of early-onset diabetes with microcephaly, epilepsy and intellectual disability.Research design and methodsWe report a Chinese young patient who was diagnosed with diabetes mellitus as a result of a TRMT10A mutation.ResultsA homozygous mutation c.496–1G>A in TRMT10A was identified using targeted next-generation sequencing and confirmed by PCR/Sanger sequencing. In addition to being diagnosed with diabetes, the patient also has microcephaly and intellectual deficiency. The diabetes was due to marked insulin resistance and responded very well to metformin treatment.ConclusionOur case is the first report in the Asian population. It adds to current knowledge of TRMT10A related with young-onset non-insulin-dependent diabetes and confirms the a single previous report of insulin resistance in this syndrome. Genomic testing should be considered in children with non-insulin-dependent diabetes with intellectual disability and microcephaly. A clear genetic diagnosis is helpful for early detection and treatment addressing insulin resistance.

scholarly journals Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene

2020 ◽  
Vol 13 (12) ◽  
pp. e235972
Author(s):  
Willem M A Verhoeven ◽  
Jos I M Egger ◽  
Paddy K C Janssen ◽  
Arie van Haeringen
Keyword(s):  
Intellectual Disability ◽  
Sleep Disturbances ◽  
Speech Development ◽  
Adolescent Male ◽  
Homozygous Mutation ◽  
Phenotypic Profile ◽  
Severe Intellectual Disability ◽  
Age Regression ◽  
General Improvement ◽  
The Central Nervous System

Histamine is involved in various physiological functions like sleep–wake cycle and stress regulation. The histamine N-methyltransferase (HNMT) enzyme is the only pathway for termination of histamine neurotransmission in the central nervous system. Experiments with HNMT knockout mice generated aggressive behaviours and dysregulation of sleep–wake cycles. Recently, seven members of two unrelated consanguineous families have been reported in whom two different missense HNMT mutations were identified. All showed severe intellectual disability, delayed speech development and mild regression from the age of 5 years without, however, any dysmorphisms or congenital abnormality. A diagnosis of mental retardation, autosomal recessive 51 was made. Here, we describe a severely mentally retarded adolescent male born from second cousins with a homozygous mutation in HNMT. His phenotypic profile comprised aggression, delayed speech, autism, sleep disturbances and gastro-intestinal problems. At early age, regression occurred. Treatment with hydroxyzine combined with a histamine-restricted diet resulted in significant general improvement.

A homozygous mutation inSLC1A4in siblings with severe intellectual disability and microcephaly

2015 ◽  
Vol 88 (1) ◽  
pp. E1-E4 ◽  
Author(s):  
M. Srour ◽  
F. F. Hamdan ◽  
Z. Gan-Or ◽  
D. Labuda ◽  
C. Nassif ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Homozygous Mutation ◽  
Severe Intellectual Disability

scholarly journals A syndrome of congenital microcephaly, intellectual disability and dysmorphism with a homozygous mutation in FRMD4A

2014 ◽  
Vol 23 (12) ◽  
pp. 1729-1734 ◽  
Author(s):  
Dina Fine ◽  
Hagit Flusser ◽  
Barak Markus ◽  
Zamir Shorer ◽  
Libe Gradstein ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Homozygous Mutation ◽  
Congenital Microcephaly
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