Search

Introduction: Early onset retinal degeneration associated with obesity can present a diagnostic challenge in paediatric ophthalmology practice. Clinical overlap between Bardet-Biedl syndrome (BBS) and Alström syndrome has been described, although the two entities are genetically distinct. To date, 16 genes are known to be associated with BBS (BBS1-16) and only one gene has been identified for Alström syndrome (ALMS1)., Materials and Methods: In collaboration with the French National Center for Sequencing (CNS, Evry), all coding exons and flanking introns were sequenced for 27 ciliopathy genes (BBS1-12, MGC1203, TTC21b, AHI1, NPHP2-8 (NPHP6=BBS14), MKS1(BBS13), MKS3, C2ORF86, SDCCAG8, ALMS1) in 96 patients referred with a clinical diagnosis of BBS. ALMS1 gene analysis included sequencing of all coding exons., Results: BBS known gene mutations were found in 44 patients (36 with two mutations and 8 heterozygous). ALMS1 mutations were found in four cases. The rate of ALMS1 mutations among patients suspected of having BBS was 4.2%., Discussion: Clinically, all four patients presented early-onset severe retinal degeneration with congenital nystagmus associated with obesity. The difficult early differential diagnosis between the two syndromes is outlined. One mutation had already been reported (c.11310delAGAG/p.R3770fsX) and three were novel (c.2293C > T/p.Q765X, c.6823insA/p.R2275fsX, c.9046delA/p.N3016fsX)., Conclusions: Ciliopathy genes sequencing can be very helpful in providing a timely diagnosis in this group of patients, hence appropriate genetic counselling for families and adequate medical follow-up for affected children.

We report here on the chromosomal mapping of the adrenoleukodystrophy-related (ALDR) gene on both the human and the mouse genomes. This gene encodes a peroxisomal ATP binding cassette transporter, closely related to the transporter identified as responsible for the adrenoleukodystrophy phenotype. ALDR maps on the syntenic region on murine and human autosomes. In addition, we could determine its position in relation to known microsatellite framework markers; this will allow to test its role in Zellweger syndrome and/ or related peroxisomal disorders.

The ability of macrophage colony-stimulating factor (M-CSF) to influence production of complement proteins by cultured human monocytes was studied. Three-day-old cultures of human monocytes were treated with 250-1000 U/ml recombinant human M-CSF (Cetus Corporation, Emeryville, CA). After 3 days the M-CSF containing medium was replaced by the same medium without M-CSF, and the cells were cultured for 3 more days. Samples taken at the removal of M-CSF and 3 days later were tested for the concentration of factor B and Cl-esterase inhibitor (CI-INH) using ELISA methods, and C2 by using an immunohaemolytic assay. M-CSF induced a marked dose- dependent increase in the synthesis of CI-INH, but did not significantly change Bf and C2 production. The findings suggest that M-CSF is able to influence selectively the complement protein-producing ability of cultured human monocytes. [ABSTRACT FROM AUTHOR]