Posts By: pcampeau

Hyperammonemia pathophysiology

Posted by & filed under Part 08: AMINO ACIDS, Treatment.

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 […]

DOOR syndrome (or DOORS syndrome) genetics

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

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 ( 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

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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.

Posted by & filed under New IEM, Part 16: LYSOSOMAL DISORDERS, Part 22: CONNECTIVE TISSUE.

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

Posted by & filed under Part 08: AMINO ACIDS, Part 16: LYSOSOMAL DISORDERS.

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 […]

Mutations in histone acetyltransferase KAT6B cause Genitopatellar syndrome.

Posted by & filed under Exome sequencing, Part 22: CONNECTIVE TISSUE, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

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

Posted by & filed under New IEM.

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 deficiency revealed a new inborn error of formylation. This study by the groups of David Thorburn and […]

Glycerol-3-Phosphate Dehydrogenase deficiency

Posted by & filed under Exome sequencing, New IEM.

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 […]