In the recent edition of Molecular Genetics and Metabolism, P. Dickson and J. Tolar discuss the potential of individual investigational new drug applications (iINDs) for N-of-One therapeutic trials of experimental therapies in inborn errors of metabolism (Mol Gen Metab 116 (2015):1-3). They discuss “pros”: faster bench to bedside translation, treating life-threatening conditions with no other therapeutic options, and “cons”: […]
Posts By: Hilary Vernon
ACVR1 R206H receptor mutation: a “gain of function” mutation cause of fibrodysplasia ossificans progressiva
Hatsell et al (Sci Transl Med. 2015 Sep 2;7(303):303ra137. doi: 10.1126/scitranslmed.aac4358) recently published very exciting work on the mechanism of the common ACVR1 gene mutation underlying fibrodysplasia ossificans progressive (FOP). This mutation confers the ability of the BMP 1 receptor ACVR1 to respond to the inflammatory response ligand Activin A, and induce bone formation. This mechanism explains […]
Heimler Syndrome: a mild peroxisome biogenesis disorder
Peroxisome biogenesis disorders are generally considered to be severe multisystem disorders, often with a progressive component. However, Ratbi et al, in the recent edition of American Journal of Human Genetics (2015 (97): 535-545) report that Heimler Syndrome, a disorder of hearing loss, abnormal dentition and nails, with or without retinitis pigmentosa, is due to hypomorphic […]
Post-zygotic Point Mutations
My general practice in counseling families with a child who has a suspected “de novo” dominant disorder is to estimate an approximate 5% recurrence risk for their future children based on potential gonadal mosaicism in the parents. However, a recent paper by Acuna-Hidalgo et al (AJHG, Volume 97, Issue 1, p67–74, 2 July 2015) presented work in which they found […]
Propofol use in methylmalonic acidemia
Our department’s general practice when advising on patients with organic acidemias who require surgery is to avoid the use of propofol. This practice was developed after a patient with methylmalonic acidemia (MMA) developed pancreatitis after a surgical procedure during which profofol was administered. However a recent review of the anesthesia administration in a cohort of 28 patients […]
LONP1 mutations in CODAS Syndrome
Dikoglu et al (AJMG 2015 Volume 167, Issue 7, pages 1501–1509) report the identification of the gene responsible for CODAS syndrome, an ultra- rare syndrome named for its’ cardinal features: Cerebral, ocular, dental, auricular, and skeletal anomalies. The responsible gene, LONP1, likely plays a role in protein turnover within the mitochondrial matrix. Thus, this represents another unique mechanism for a primary disorder […]
Congenital anomalies of the kidneys and urinary tract and TBX18
Until a recent publication by Vivante et al, in the American Journal of Human genetics (July 2015, available on-line, in press), genes responsible for Congenital anomalies of the kidneys and urinary tract (CAKUT) were elusive. They identified 4 families with dominant negative mutations in TBX18. The mechanism of pathogenicity is thought to be interference with TBX18 transcriptional […]
Variants in SLC6A1 and Doose Syndrome
Doose Syndrome, also known as myoclonic-astatic epilepsy, is a form of epilepsy in which the genetic etiology has been somewhat elusive. A recent study by Carvill et al (Am J Hum Genet 2015 May 7;96(5):808-15. doi: 10.1016/j.ajhg.2015.02.016) reports that pathogenic variants in GAT-1, encoded by SLC6A1, can be responsible for up to 4% of cases of myoclonic-astatic epilepsy. Carvill et al. focused on this gene […]
ECHS1 deficiency and mitochondrial disease
Haack et al (Annals of Clinical and Translational Neurology, 2015, 2 (5) pp. 492-509) recently reported a disorder of encephalopathy, deafness, optic atrophy, and cardiomyopathy caused by mutations in short-chain enoyl-CoA hydratase (ECHS1). This mitochondrial matrix enzyme functions in the oxidation of fatty acids and some amino acids (particularly valine). Patients present with a wide range […]
Risk of tumors in Bohring-Opitz Syndrome
Bohring-Opitz Syndrome (BOS, MIM 612990) is a rare condition characterized by dysmorphic features, failure to thrive, severe intellectual disability, nevus flammeus and myopia. It can be caused by heterozygous mutations in ASXL1, a gene involved in the regulation of Hox genes. Russel et al. (AJMG, 2015, Apr 29. doi: 10.1002/ajmg.a.37131. [Epub ahead of print]) just published clinical management […]
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