Association of a de novo 16q copy number variant with a phenotype that overlaps with Lenz microphthalmia and Townes-Brocks syndromes

<p>Abstract</p> <p>Background</p> <p>Anophthalmia and microphthalmia are etiologically and clinically heterogeneous. Lenz microphthalmia is a syndromic form that is typically inherited in an X-linked pattern, though the causative gene mutation is unknown. Townes-Brocks syndrome manifests thumb anomalies, imperforate anus, and ear anomalies. We present a 13-year-old boy with a syndromic microphthalmia phenotype and a clinical diagnosis of Lenz microphthalmia syndrome.</p> <p>Case Presentation</p> <p>The patient was subjected to clinical and molecular evaluation, including array CGH analysis. The clinical features included left clinical anophthalmia, right microphthalmia, anteriorly placed anus with fistula, chordee, ventriculoseptal defect, patent ductus arteriosus, posteriorly rotated ears, hypotonia, growth retardation with delayed bone age, and mental retardation. The patient was found to have an approximately 5.6 Mb deletion of 16q11.2q12.1 by microarray based-comparative genomic hybridization, which includes the <it>SALL1 </it>gene, which causes Townes-Brocks syndrome.</p> <p>Conclusions</p> <p>Deletions of 16q11.2q12.2 have been reported in several individuals, although those prior reports did not note microphthalmia or anophthalmia. This region includes <it>SALL1</it>, which causes Townes-Brocks syndrome. In retrospect, this child has a number of features that can be explained by the <it>SALL1 </it>deletion, although it is not clear if the microphthalmia is a rare feature of Townes-Brocks syndrome or caused by other mechanisms. These data suggest that rare copy number changes may be a cause of syndromic microphthalmia allowing a personalized genomic medicine approach to the care of patients with these aberrations.</p

Pseudomonas aeruginosa cross-colonization and persistence in patients with cystic fibrosis. Use of a DNA probe.

To investigate cross-colonization with and persistence of Pseudomonas aeruginosa in cystic fibrosis (CF), 181 isolates from 76 CF patients were typed using a P. aeruginosa-specific DNA probe. Whereas sibling pairs predominantly harboured genotypically identical P. aeruginosa strains, all of the other patients harboured different strains. Seventy-nine per cent (22/31) of the infected CF patients harboured the same strains at the beginning and the end of a summer camp. A change of strains was seen in 10% (3/31) of the patients at the end of the camp. Forty-six per cent (6/13) of the patients who were apparently initially uninfected, acquired P. aeruginosa by the end of the period. Genotyping proved that strain change or acquisition was due to cross-colonization in four of nine cases. Very little P. aeruginosa was isolated from the inanimate environment. Persistence of P. aeruginosa after a temporary loss due to antibiotic therapy was seen in 12/16 paired patient strains before and after antibiotic therapy. Thus, suppression followed a flare-up seemed to occur in these patients rather than eradication and a new infection. When 35 patients were followed over a period of 6 months, 7 (20%) changed the strain in their sputum. Only one of 43 patients harboured two different P. aeruginosa strains simultaneously over a long period