Expanded Phenotypic Spectrum or Multiple Syndromes?

[摘要] From time to time patients with a spectrum of phenotypes that do not clearly fit into a known syndrome areencountered. Then clinical geneticists have to decidewhether this particular patient has a syndrome with anexpanded phenotypic spectrum or something entirelydifferent. As a matter of routine, chromosomal microarrays are performed [Miller et al., 2010]. The outcome ofthis test may be a chromosomal deletion or may be unremarkable, which then prompts whole-exome or evenwhole-genome sequencing, or, if a chromosomal deletionencompasses several OMIM genes, one has to consider acontiguous gene syndrome. For this, the genes affected bythe deletion should be gene dosage sensitive, i.e., loss ofone allele will provoke a clinical phenotype by a dominantmechanism. Such cases of contiguous gene syndromesare frequently seen in pediatric genetics. In addition, patients with a combination of a chromosomal deletion andan autosomal recessive disorder have been reported[Flipsen-ten Berg et al., 2007]. This constellation ariseswhen a deletion of a segment of one chromosome coincides with a recessive mutation in a gene on the other,intact chromosome. This mechanism, known as “unmasking” of recessive mutations, has been reported for atleast 23 cases.

[学科分类] 基础医学