Posts Categorized: Exome sequencing



Whole Exome Sequencing in Inborn errors of metabolism

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES.

Therapies are becoming increasingly avaible for inborn errors of metabolism making diagnosis of these disorders particularly improtant. The New England Journal of Medicine recently published a study on whole-exome sequencing in 41 patients resulting in a diagnosis in 28 of them (68%) and a targeted intervention in 18 of them (44%). The relatively high diagnostic yield found in this study may stem […]



Somatic mutation in single human brain cells

Posted by & filed under Exome sequencing, Part 03: GENERAL THEMES, Part 28: NEUROGENETICS.

Neurons live for decades in a postmitotic state and their genomes are susceptible to DNA damage. Using genome sequencing for individual human brain cells (postmortem), Lodato et al. have searched for somatic single-nucleotide variants (SNVs) in the human brain. After sequencing 36 neurons from the cerebral cortex of three normal individuals, they demonstrated that the […]



Progress in nanopore technology

Posted by & filed under Exome sequencing, In the news, Part 06: DIAGNOSTIC APPROACHES, Tools.

Feng et al. (2015) recently reviewed the progress in nanopore technology from the past as well as the latest advances. They describe the different types of nanopores and discuss recent and potential applications. Nanopore-based sequencers have the potential to quickly and reliably sequence the entire human genome “for less than $1000, and possibly for even […]



New phenotype associated with phosphoribosyl pyrophosphate synthetase 1 deficiency

Posted by & filed under Exome sequencing, Part 11: PURINES AND PYRIMIDINES.

Al-Maawali A et al. Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders. European Journal of Human Genetics (2015) 23, 310–316.   Phosphoribosyl pyrophosphate synthetase 1 (PRS-1) catalyses the first step of purine synthesis, and several X-linked disorders have been associated with both its deficiency (Arts syndrome, […]



A2ML1 mutations are associated with a Noonan-like syndrome

Posted by & filed under Exome sequencing, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

Vissers L et al. Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome. European Journal of Human Genetics (2015) 23, 317-324.   For a quarter of patients clinically diagnosed with Noonan syndrome, the molecular cause cannot be identified. Through exome sequencing in a case-parent trio, followed by targeted resequencing […]



A framework for the interpretation of de novo mutation in human disease

Posted by & filed under Exome sequencing, Part 28: NEUROGENETICS.

Samocha et al. A framework for the interpretation of de novo mutation in human disease. Nat Genet. 2014 Aug 3.   Samocha et al describe a sophisticated statistical model designed to better evaluate data derived from mass exome sequencing studies, specifically with respect to the significance of excesses of de novo mutations in diseases with […]



New monogenic early-onset polyautoimmunity syndrome caused by activating mutations in STAT3

Posted by & filed under Exome sequencing, Part 20: IMMUNE AND DEFENSE SYSTEMS.

Flanagan SE et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.Nat Genet. 2014 Aug;46(8):812-4. Monogenic autoimmunity syndromes are a rare cause of very early-onset multiple autoimmune manifestations. Flanagan et al report a new monogenic early-onset polyautoimmunity syndrome caused by activating STAT3 mutations. They initially used exome sequencing to identify an activating de novo […]



New genomic technologies, PGD/Prenatal Genetics and society

Posted by & filed under Exome sequencing, Part 03: GENERAL THEMES, Part 06: DIAGNOSTIC APPROACHES.

As in every other field of science, the experts in medical genetics should collaborate closely with policy and law-makers to guide the usage of the new technologies. This is particularly important at present time in the context of the advancement of genomic technologies. A recent article by Farra et al. (retrospective cohort study) published in […]



Exome sequencing redefining phenotypes

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

One would intuitively expect that Whole-exome sequencing (WES) will help broaden the phenotypic spectrum of known syndromes since in the past only patients closely matching the described phenotype of a documented genetic syndrome would be tested for the respective diagnosis. Some recent examples illustrating the direction the field is moving include the publications of Dr. […]



Mitochondrial disease and Sideroflexin 4

Posted by & filed under Exome sequencing.

Hildick-Smith et al (AJHG, 2013, 5(93) 906-914) used whole exome sequencing in two probands with mitochondrial disease to identify SFXN4 as a candidate gene for the etiology of their disorder. They then were able to take advantage of fibroblast complementation assays  and a zebrafish knockdown model to validate SFXN4 as the causative gene. With increasing utilization of whole exome sequencing […]