The mechanisms leading to the toxicity of hyperammonemia have been long known to be complex. For a review of what was known in 2012, see this article: Auron A, Brophy PD. Pediatr Nephrol. 2012 Feb;27(2):207-22. doi: 10.1007/s00467-011-1838-5. Epub 2011 Mar 23. Hyperammonemia in review: pathophysiology, diagnosis, and treatment. In this review, they discuss amino acid […]
Posts By: pcampeau
DOOR syndrome (or DOORS syndrome) genetics
In this post, I will describe one of my main research projects, the study of DOOR syndrome, or DOORS syndrome, which stands for : – Deafness (sensorineural) – Onychodystrophy (abnormal nails) – Osteodystrophy (abnormal bones, especially in the digits) – Retardation, mental (now know as intellectual disability) – Seizures The acronym was first used by […]
Yunis-Varón syndrome gene identification links this skeletal dysplasia with neurological involvement to phosphoinositide metabolism
Yunis-Varón syndrome is a skeletal dyplasia with features of cleidocranial dysplasia, with digital hypoplasia and severe neurological involvement (http://omim.org/entry/216340). Through exome sequencing, we identified three families with mutations of FIG4, encoding a phosphoinositide phosphatase. This enzyme had previously been implicated in Charcot-Marie-Tooth type 4J (CMT-4J). While CMT-4J is usually caused by a combination of a […]
Gene therapy for ethylmalonic encephalopathy
Ethylmalonic encephalopathy is caused by a deficiency of a mitochondrial sulfur dioxygenase (leading to the accumulation of sulfides in mitochondria, which impair mitochondrial energy metabolism). Ethylmalonic encephalopathy is characterized by neurodevelopmental delay and regression, prominent pyramidal and extrapyramidal signs, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. Now, using an adeno-associated virus to deliver the ETHE1 […]
Mutations in the nucleoside transporter gene SLC29A3 cause dysosteosclerosis, a form of osteopetrosis.
SLC29A3 is a lysosomal nucleoside transporter mutations in which cause histiocytosis–lymphadenopathy plus syndrome, a group of conditions with little or no skeletal involvement. We have now identified mutations in this gene in dysosteosclerosis, a form of osteopetrosis characterized by the additional features of platyspondyly, remarkable acquired metaphyseal osteosclerosis and red-violet macular atrophy of skin. We […]
Lysosomal Lysine/Arginine Transporter Identified
In a forward genetic screen in C. elegans, Liu et al. identified LAAT-1, and its human counterpart PQLC2 as the lysosomal lysine/arginine transporter. Without this transporter, lysosomes become filled with arginine and lysine and this can cause cell death. Mutations in PQLC2 have not yet been identified in humans with lysosomal disorders. Liu B, Du […]
Targeting nuclear RNA to the mitochondria
A group headed by Dr. Carla M. Koehler at UCLA has just published the use of an RNA stem-loop sequence from H1 RNA, the RNA component of the human RNase P enzyme, to target other nuclear encoded RNAs to the mitochondria. They demonstrated a potential therapeutic use by modifying the mt-tRNAs with this sequence, encode […]
Mutations in histone acetyltransferase KAT6B cause Genitopatellar syndrome.
Sorry to blow my own horn but I’m quite passionate about the findings described below. Late last year, the group of Clayton-Smith et al. identified mutations in KAT6B in Ohdo syndrome, a condition characterized by blepharophimosis and developmental delay. Shortly after, our group and the group of Simpson et al. identified mutations in the same […]
Inborn error of tRNA formylation
Tucker EJ, et al. Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metab. 2011 Sep 7;14(3):428-34 Next-generation sequencing of nuclear-encoded mitocondrial proteins in two unrelated patients with Leigh syndrome and combined OXPHOS deï¬ciency revealed a new inborn error of formylation. This study by the groups of David Thorburn and […]
Glycerol-3-Phosphate Dehydrogenase deficiency
Basel-Vanagaite L. et al. Transient Infantile Hypertriglyceridemia, Fatty Liver, and Hepatic Fibrosis Caused by Mutated GPD1, Encoding Glycerol-3-Phosphate Dehydrogenase 1. Am J Hum Genet. 2012 Jan 4 In several individuals with childhood hypertriglyceridemia followed by liver fibrosis, this group identified mutations in GDP1, encoding Glycerol-3-Phosphate Dehydrogenase 1. The enzyme GPD1 reversibly converts glycerol-3-phosphate (G3P) in […]
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