Submicroscopic terminal deletions and duplications in retarded patients with unclassified malformation syndromes

Unbalanced submicroscopic subtelomeric chromosomal rearrangements represent a significant cause of unexplained moderate to severe mental retardation with and without phenotypic abnormalities. We investigated 254 patients (102 from Zürich, 152 from Liège) for unbalanced subtelomeric rearrangements by using fluorescence in situ hybridisation with probes mapping to 41 subtelomeric regions. Mental retardation combined with a pattern of dysmorphic features, with or without major malformations, and growth retardation and a normal karyotype by conventional G-banding were the criteria of inclusion. Selection criteria were more restrictive for the Zürich series in terms of clinical and cytogenetic pre-investigation. We found 13 unbalanced rearrangements and two further aberrations, which, following the investigation of other family members, had to be considered as variants without influence on the phenotype. The significant aberrations included three de novo deletions (two of 1pter, one of 5pter), three de novo duplications (8pter, 9pter, Xpter), one de novo deletion 13qter-duplication 4qter, and five familial submicroscopic translocations [(1q;18p), (2q;4p), (2p;7q), (3p;22q), (4q;10q), (12p;22q)], most of them with several unbalanced offspring with deletion-duplication. Although the incidence of abnormal results was higher (10/152) in the Liège versus the Zürich series (3/102), similar selection criteria in Zürich as in Liège would have resulted in an incidence of 7/106 and thus similar figures. In our series, submicroscopic unbalanced rearrangements explain the phenotype in 13/254 study probands. The most important selection criterion seems to be the presence of more than one affected member in a family. An examination of subtelomeric segments should be included in the diagnostic work-up of patients with unexplained mental retardation combined with physical abnormalities, when a careful conventional examination of banded chromosomes has yielded a normal result and a thorough clinical examination does not lead to another classification. The proportion of abnormal findings depends strongly on selection criteria: more stringent selection can eliminate some examinations but necessitates a high workload for experienced clinical geneticists. Once the costs and workload of screening are reduced, less selective approaches might finally be more cost-effective.     

A patient presenting a 22q13 deletion associated with an apparently balanced translocation t(16;22): An illustrative case in the investigation of patients with low ARSA activity

A 10-year-old speechless, mentally deficient male, with low arylsulfatase A (ARSA) activity, and presumably, methachromatic leukodystrophy, underwent genetic evaluation. As the clinical picture was not compatible with this diagnosisan ARSA gene and chromosome analysis were performed, showing the presence of a pseudodeficiency ARSA allele and a de novo apparently balanced t(16;22)(p11.2;q13) translocation. A deletion on the long arm of chromosome 22 encompassing the ARSA gene, as shown by FISH and array-CGH, indicated a 22q13 deletion syndrome. This case illustrates the importance of detailed cytogenetic investigation in patients presenting low arylsulfatase A activity and atypical/unspecific clinical features.     

Infection et fertilité —Corynebacterium seminale: point de vue du bactériologiste

The authors present two independent studies designed to identify corynebacteria isolated from the semen of patients consulting for infertility. Corynebacteria were identified by conventional biochemical and physiological tests and by determination of volatile fatty acids. In the first study based on 420 patients, the commonest species were Corynebacterium seminale (synonym C. glucuronolyticum) found in 7.4% of specimens, CDC group G (5%) and C. amycolatum (3.8%). Of the 92 semen specimens with more than 103 cfu/ml, 44 were positive for corynebacteria, including 15 C. seminale strains, whereas streptococci, staphylococci and enterobacteriacae were found in 23, 18 and 6 of the 420 specimens, respectively. The presence of C. seminale was more frequently associated with a high bacteria count than the other corynebacteria (p<0.02). In the second study, we compared the presence of corynebacteria in the semen of 1,902 patients with semen indices. C. seminale was present at levels greater than 103 cfu/ml in 2.7% of these specimens, while several other species of corynebacteria were detected in 5.3% of cases. Normal motility was found in only 25.4% of semen specimens with a high C. seminale count in contrast with 45% of specimens containing similar counts of other corynebacteria. These studies demonstrate that the isolation rates from human genital specimens and their clinical implications are different according to the species isolated. Microbiologists should be aware of the need to accurately identify these corynebacteria for further in vitro or in vivo studies on genital infections.     

Physiology engages with functional genomics - at last

A report on the XXXV International Congress of Physiological Sciences, held together with Experimental Biology 2005, San Diego, USA, 31 March - 6 April 2005.     

Neutralizing determinants defined by monoclonal antibodies on polypeptides specified by bovine herpesvirus 1.

Monoclonal antibodies were used to study neutralizing determinants on polypeptides of bovine herpesvirus 1. Two of three monoclonal antibodies which recognized nonoverlapping epitopes on a glycoprotein of 82,000 daltons were found to neutralize. A second group of monoclonal antibodies that individually precipitated five viral glycopolypeptides ranging in size from 102,000 to 55,000 daltons also neutralized. Two monoclonal antibodies which were the most efficient in neutralization recognized a non-glycosylated protein of 115,000 daltons which was the major polypeptide on the virus. A fourth group of monoclonal antibodies precipitated a non-glycosylated polypeptide of 91,000 daltons and several smaller polypeptides, but these antibodies demonstrated only limited neutralizing activity.