Somatic mosaicism for a PDHA1 mutation in a female with pyruvate dehydrogenase deficiency.

Human Genetics
C K RidoutGarry K Brown

Abstract

Somatic mosaicism for a mutation in the X-linked PDHA1 gene was found in a girl who presented with manifestations of pyruvate dehydrogenase deficiency. Mutation in the PDHA1 gene was suggested by a mosaic pattern of E1alpha subunit immunostaining; however, initial screening of cDNA and the exons and intron-exon boundaries yielded only normal sequence, apart from a heterozygous 4 bp insertion in intron 10. This was considered to be a polymorphism as it is also present in her unaffected mother who has normal enzyme activity and uniform E1alpha immunostaining in fibroblasts. Detailed genetic analysis, which included isolation of cloned fibroblasts expressing the mutant X chromosome, resulted in the identification of a base substitution in the acceptor splice site of intron 9 which leads to activation of a cryptic upstream splice site. The proportion of cells expressing the mutation was then determined by direct analysis of the X-inactivation pattern. Genetic diagnosis in this unique case of PDHA1 somatic mosaicism was complicated by the absence of an abnormal transcript in primary fibroblasts, the presence of three different alleles and an X-inactivation pattern favouring expression of the normal, paternal, X chromosome. Although ...Continue Reading

References

Oct 1, 1986·The Biochemical Journal·C A WickingG K Brown
Feb 1, 1986·The Journal of Pediatrics·M L BatshawJ Trojak
Nov 1, 1994·Journal of Medical Genetics·G K BrownR M Brown
Jun 1, 1994·Prenatal Diagnosis·R M Brown, G K Brown
Mar 1, 1993·Journal of Medical Genetics·R M Brown, G K Brown
Jan 1, 1997·Human Genetics·T YorifujiK Furusho
Feb 1, 1997·Journal of Medical Genetics·R FroissartD Bozon
Jul 1, 1997·Journal of Molecular Evolution·I B Rogozin, L Milanesi
Jul 6, 2000·European Journal of Human Genetics : EJHG·S TinschertD E Jenne
Jun 19, 2001·American Journal of Human Genetics·M LeuerK Olek
Jan 5, 2002·Journal of Inherited Metabolic Disease·A SeydaB H Robinson
Jun 19, 2002·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Margarita Y LibRoderick A Capaldi
Oct 3, 2002·Nature Reviews. Genetics·Hagop Youssoufian, Reed E Pyeritz
Mar 20, 2003·Mutation Research·Robert P Erickson
Aug 19, 2004·American Journal of Medical Genetics. Part a·William B DobynsCarole Ober

❮ Previous
Next ❯

Citations

Mar 24, 2009·Journal of Inherited Metabolic Disease·J H Walter
Jul 5, 2011·Pediatric Neurology·Nicholas Ah MewAdeline Vanderver
Apr 20, 2010·Mutation Research·Robert P Erickson
Aug 20, 2018·International Journal of Cancer. Journal International Du Cancer·Tereza GoliasIoanna Papandreou
Jun 8, 2018·Journal of Inherited Metabolic Disease·Jean-Marie Saudubray, Fanny Mochel

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.