Bezafibrate for Sjögren-Larsson syndrome

Posted by & filed under Part 12: LIPIDS.

Sjögren-Larsson syndrome presents with ichtyosis, spastic diplegia and cognitive deficits. It is caused by a deficiency of fatty aldehyde dehydrogenase. Treatments are limited to symptomatic therapies; for example, ziluteon (an inhibitor of 5-lipoxygenase) can reduce pruritus.

In a recent article, bezafibrate has been shown to induce the expression of the deficient protein in fibroblasts from some patients. This discovery could become of clinical importance.
Mol Genet Metab. 2006 September – October;89(1-2):111-115.

Bezafibrate induces FALDH in human fibroblasts; implications for Sjogren-Larsson syndrome.

Gloerich J, Ijlst L, Wanders RJ, Ferdinandusse S.

For an excellent review of Sjögren-Larsson syndrome, see this article in which we learn that a knockout mouse has been created for this condition :

Mol Genet Metab. 2006 Sep 20;

Sjogren-Larsson syndrome: Molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency.

Rizzo WB.

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Microdeletion 17q21.31 syndrome

Posted by & filed under Part 05: CHROMOSOMES, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

In the September 2006 issue of Nature Genetics, three groups identify a new microdeletion syndrome (microdeletion 17q21.31). The major clinical features of this syndrome are severe hypotonia and moderate mental retardation
See the News and Views article by James R. Lupski:

Nat Genet. 2006 Sep;38(9):974-6.

Genome structural variation and sporadic disease traits.

Lupski JR.

James R. Lupski is in the Department of Molecular and Human Genetics and the
Department of Pediatrics, Baylor College of Medicine and Texas Children’s
Hospital, Houston, Texas, USA.
See also the artcles by Koolen DA et al., Shaw-Smith C et al. and Sharp J et al.

 

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Posted by & filed under Part 19: BLOOD.

Nat Genet. 2003 Jun;34(2):157-65.

Transcription of antisense RNA leading to gene silencing and methylation as a
novel cause of human genetic disease
.

Tufarelli C, Stanley JA, Garrick D, Sharpe JA, Ayyub H, Wood WG, Higgs DR.

In this article, Tufarelli and colleagues describe a new genetic mechanism of human disease, in a patient with alpha-thalassemia. A deletion in a nearby gene, LUC7L, causes antisense mediated cis-acting methylation and silencing of the HBA2 gene.

For more information on the epigenetic silencing of genes, please see chapter 18.1

For more information on thalassemia, please see chapter 181.
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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator
 

Genome Canada International Conference

Posted by & filed under Meetings.

Genome Canada is holding an Intenational Conference entitled:

2020 Vision: Variation and Function in the Genome

October 25th to 27th in beautiful Château Fronenac, in Québec city, Canada.

Here is the conference program.

 

Philippe Campeau

High Incidence of Later-Onset Fabry Disease Revealed by Newborn Screening

Posted by & filed under Newborn screening, Part 02: PERSPECTIVES, Part 16: LYSOSOMAL DISORDERS.

Am. J. Hum. Genet., 79:000, 2006

High Incidence of Later-Onset Fabry Disease Revealed by Newborn Screening
Marco Spada, Severo Pagliardini, Makiko Yasuda, Turgut Tukel, Geetha Thiagarajan, Hitoshi Sakuraba, Alberto Ponzone, and Robert J. Desnick
In this article, alpha-galactosidase A activity was assayed in newborn screening blood spots of Italian male neonates. This study revealed a high incidence of later-onset Fabry disease.

For more information on Fabry disease, see chapter 150 of OMMBID.
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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Diagnosing inborn errors of lipid metabolism with proton NMR spectroscopy

Posted by & filed under Part 12: LIPIDS.

In this publication, NMR is used to diagnose or follow patients with 4 different inborn errors of lipid metabolism:
Smith-Lemli-Opitz syndrome
Cerebrotendinous Xanthomatosis
Sitosterolemia
Refsum disease
This technique might have a widespread clinical use in the future, given its advantages (authetic standards often unnecessary, almost unequivocal lipid identification, and easy sample preparation).

Clin Chem. 2006 Jul;52(7):1395-405. Epub 2006 May 18.

Diagnosing inborn errors of lipid metabolism with proton nuclear magnetic
resonance spectroscopy.

Oostendorp M, Engelke UF, Willemsen MA, Wevers RA.
For more information on inherited disorders of lipid metabolism, see part 12 of OMMBID.

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Wagner syndrome

Posted by & filed under Part 29: EYE.

Wagner syndrome (hyaloideoretinal degeneration of Wagner) is an autosomal dominant vitreoretinopathy. It manifests at childhood or adolescence and is progressive. In the original Swiss kindred, most patients had an “empty” vitreous cavity with avascular strands or veils. The molecular cause for this condition in the original kindred was recently identified:

Mol Vis. 2006 Apr 17;12:350-5.
Identification of the genetic defect in the original Wagner syndrome family.
Kloeckener-Gruissem B, Bartholdi D, Abdou MT, Zimmermann DR, Berger W.

For more information on inherited disorders of the eye, see part 29 of OMMBID.

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Pyridoxine dependent epilepsy

Posted by & filed under Part 08: AMINO ACIDS.

Pyridoxine dependent epilepsy (PDE) was first described by Hunt in 1954. In 1969, Dr Scriver suggested that PDE was caused by reduced binding of pyridoxal phosphate to glutamate decarboxylase leading to buildup of excitotoxic glutamate and deficiency of inhibitory GABA in the brain.

 
In 2005, a group identified the gene ALDH7A1 encoding antiquitin (P6C-alpha-AASA dehydrogenase) as the culprit in PDE. This astute discovery was made following the report of pipecolic acid accumulation in PDE and by hypothesizing that P6C inactivates pyridoxal phosphate in a similar fashion as P5C in hyperprolinemia type II.
 

Nat Med. 2006 Mar;12(3):307-9. Epub 2006 Feb 19.
Mutations in antiquitin in individuals with pyridoxine-dependent seizures.
Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA,
Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT.

For great reviews, see:

J Inherit Metab Dis. 2006 Apr;29(2-3):317-26.
B(6)-responsive disorders: A model of vitamin dependency.
Clayton PT.

OMMBID chapter 86.1.
 

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

The Orphanet Journal of Rare Diseases

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

Orphanet continues its quest to to improve the management and treatment of genetic, auto-immune or infectious rare diseases, rare cancers, or not yet classified rare diseases.
It launched the Orphanet Journal of Rare Diseases. The editors in chief are Ségolène Aymé, Inserm, Hôpital Broussais; Bruno Dallapiccola, Istituto CSS-Mendel; and Dian Donnai,The Victoria University of Manchester.

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator