NOVEL HOMOZYGOUS VARIANT OF TBC1 DOMAIN FAMILY MEMBER 8 GENE IN FOUR LIBYAN SIBLINGS WITH AUTISTIC SPECTRUM DISORDER AND INTELLECTUAL DISABILITY WITHOUT EPILEPSY

Objective: Recent progress in genetic analysis and investigations have enabled researchers to identify potential genetic changes that may play a role in ASD. The number of genes connected with autism is growing. Whole exome sequencing(WES) identified the homozygous TBC1D8 variant. Aim to report for the first time a TBC1D8 missense variant (c.1883G>A, p. (Arg628Gln) in 4 Libyan children (3 homozygous,1 heterozygous) with severe neurodevelopmental phenotypes ASD and intellectual disability ID . Based on the data of HGMD and ClinVar, variants in only a few autosomal recessive intellectual disability ARID genes seem to be reported frequently. Method: Molecular genetic analysis of (WES) was carried out on blood samples from these children. The outcome of the genetic investigations was interpreted within the context of clinical finding, family history, and suspected mode of inheritance. Results: The number of genes associated with autism is increasing. WES identified the TBC1D8 variant. According to the longest isoform (NM_001102426.1),the nomenclature of this variant is c.1883G>A, p. (Arg628Gln) in TBC1D8 which leads to an amino acid exchange. This variant has not previously reported or described in the literature (PubMed, HGMD). Conclusion: we have provided evidence for a connection between TBC1D8 variant and ASD and ID; however, this evidence should be considered preliminary in the context of a single case report and such findings need to be replicated to gain insight in order to determine if ASD and ID are a characteristic of this variant.

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Congenital Orbital Fibrosis: Molecular Genetic Analysis by Whole-Exome and Mitochondrial Genome Sequencing

Yonsei Medical Journal ◽

10.3349/ymj.2017.58.5.1078 ◽

2017 ◽

Vol 58 (5) ◽

pp. 1078

Author(s):

JaeSang Ko ◽

Hyun-Joo Lee ◽

Jin-Sung Lee ◽

Jin Sook Yoon

Keyword(s):

Mitochondrial Genome ◽

Genetic Analysis ◽

Genome Sequencing ◽

Molecular Genetic ◽

Molecular Genetic Analysis ◽

Whole Exome

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The genetic analysis of growth and body composition in the mouse as a livestock model

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200011509 ◽

2005 ◽

Vol 2005 ◽

pp. 239-239

Author(s):

W. G. Hill ◽

L. Bünger

Keyword(s):

Body Composition ◽

Food Intake ◽

Genetic Analysis ◽

Molecular Genetic ◽

Genetic Research ◽

Molecular Genetic Analysis ◽

Genetic Changes ◽

Livestock Breeding ◽

Farm Livestock ◽

Human Genetic Research

The similarities between the mouse and farm livestock at the genetic and functional level make it a useful model for farm livestock breeding and indeed for human genetic research, taking the opportunities presented by its short generation interval, the development of inbred lines, and the ability to do gene knock-outs. Genetic similarities apply both at the molecular level, in gene structure and sequence, and at the quantitative level, for example genetic parameters of growth. We discuss here what can be learnt about the action and interaction of genes that influence traits of growth and body composition and contribute to genetic changes in them from work on the mouse, concentrating particularly on candidate genes and experiments conducted in our laboratory. As a resource we have developed highly divergent selection lines for growth, body composition and food intake, brought together lines of mice selected for growth from around the world, and inbred them both for stability and to facilitate their use for molecular genetic analysis. These lines differ greatly as a consequence of selection not only in growth and degree of fatness, but also in efficiency, as assessed by food intake corrected for body weight.

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Schinzel—Giedion Syndrome: First Czech Patients Confirmed by Molecular Genetic Analysis

Journal of Pediatric Neurology ◽

10.1055/s-0038-1651520 ◽

2018 ◽

Vol 17 (03) ◽

pp. 125-127

Author(s):

Jana Neupauerová ◽

Katalin Štěrbová ◽

Vladimír Komárek ◽

Andrea Gřegořová ◽

Markéta Vlčková ◽

...

Keyword(s):

Genetic Analysis ◽

Sanger Sequencing ◽

De Novo ◽

Genetic Disorder ◽

Molecular Genetic ◽

Molecular Genetic Analysis ◽

Facial Features ◽

De Novo Mutations ◽

Whole Exome ◽

Exon 4

AbstractSchinzel–Giedion syndrome (SGS) is a very rare genetic disorder characterized by distinctive facial features, severe developmental delay, seizures, and skeletal abnormalities. Whole exome sequencing, Sanger sequencing, and correlation with already published variants and cases allowed us to identify two different de novo mutations in the SETBP1 gene: NM_015559.2 (SETBP1): c.2601C > G (p.Ser867Arg) and c. 2608 G > A (p.Gly870Ser) in two Czech patients presenting with SGS features. Both mutations are within exon 4 of SETBP1, supporting the notion that exon 4 represents the mutation hotspot of the gene in patients with SGS.

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Familial Optic Disc Pits in 2 Father-Son Pairs: Clinical Features and Genetic Analysis

Case Reports in Ophthalmology ◽

10.1159/000515972 ◽

2021 ◽

pp. 603-610

Author(s):

Devin Betsch ◽

Andrew Orr ◽

Mathew Nightingale ◽

Daniel Gaston ◽

Rishi Gupta

Keyword(s):

Genetic Analysis ◽

Optic Disc ◽

Clinical Features ◽

Molecular Genetic ◽

Case Series ◽

Molecular Genetic Analysis ◽

Ophthalmological Examination ◽

Whole Exome ◽

Disease Predisposition ◽

Causal Variants

Congenital optic disc pits (ODPs) are well-circumscribed depressions within the optic disc. Thought to arise from anomalous closure of the optic fissure during embryonic development, they are now considered to lie on a broader spectrum of congenital optic disc anomaly (CODA). An increasing number of reports describe clustering of these cases within families, suggesting that inherited genetic elements play a role in disease predisposition. Here, we highlight the clinical features of 2 sets of father-son pairs affected with ODPs and provide preliminary molecular genetic analysis. Subjects underwent complete ophthalmological examination and imaging. In addition, whole-exome sequencing was carried out following informed consent. The resulting datasets were examined for potentially causal genetic variants, both in genes already known to be linked to CODA as well as those likely to lie in the same or similar genetic pathways. In this instance, no unambiguously causal variants were identified. This case series highlights the familial inheritance of ODPs, adding to the existing body of literature supporting an underlying genetic cause for this rare clinical entity. The inclusion here of specific molecular findings raises the hope that the genetic pathophysiology underlying rare entities like ODPs might be clarified in the future by the addition of similarly molecular-documented reports.

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