Peters Plus Syndrome Is Caused by Mutations in B3GALTL, a Putative Glycosyltransferase

Molecular Cell Biology Group , Leiden University, Leyden, South Holland, Netherlands
The American Journal of Human Genetics (Impact Factor: 10.93). 10/2006; 79(3):562-6. DOI: 10.1086/507567
Source: PubMed


Peters Plus syndrome is an autosomal recessive disorder characterized by anterior eye-chamber abnormalities, disproportionate short stature, and developmental delay. After detection of a microdeletion by array-based comparative genomic hybridization, we identified biallelic truncating mutations in the beta 1,3-galactosyltransferase-like gene (B3GALTL) in all 20 tested patients, showing that Peters Plus is a monogenic, primarily single-mutation syndrome. This finding is expected to put Peters Plus syndrome on the growing list of congenital malformation syndromes caused by glycosylation defects.

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    • "region with only seven mutations reported in the literature[2]. B3GALTL mutations lead to the inactivation of the β-1,3–lucosyl-transferase involving in the synthesis of a rare disaccharide that occurs on thrombospondin type 1 repeats of many biologically important proteins[3], suggesting that the syndrome is a glycosylation disorder. "
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    ABSTRACT: Peters Plus syndrome (MIM 261540) is a rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor abnormalities. Mutations in the B3GALTL gene encoding the β-1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome. We report here a female patient with severe manifestations of Peters Plus syndrome including facial dysmorphism and bilateral corneal opacity associated with left renal pyelo-calicial dilatation and sexual ambiguity. Total sequencing of the B3GALTL gene revealed no mutation in the patient. To our knowledge, sexual ambiguity has not previously been reported in Peters Plus syndrome so far, and renal malformation is also apparently rare in the syndrome.
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    • "Thus, the tendency to call de novo CNVs pathogenic has led to a possible overestimation of the causality of de novo CNVs [Vermeesch et al., 2011], especially in the case of small CNVs (<500 kb). Moreover, when a parent carrying the same CNV as the fetus is phenotypically normal, as occurs in most cases, the pathogenicity of the CNV cannot be excluded, since (1) a gene within the deletion region located on the homologous nondeleted chromosome can be mutated, thus leading to an autosomal recessive condition [Lesnik Oberstein et al., 2006]; (2) the CNV can contain an imprinted gene that has a pathogenic effect only when inherited from the mother and not from the father, or vice versa [Kagami et al., 2010]; or (3) the CNV itself is a risk factor promoting a given disease in a specific but unknown genomic context, in other words, the CNV has its own pathogenic burden but exhibits incomplete penetrance. The last point is well demonstrated by several recurrent and frequently inherited deletions/duplications associated with different neurological phenotypes, for which a second hit is considered necessary for the full manifestation of the syndrome [Girirajan and Eichler, 2010; Girirajan et al., 2010]. "
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