Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination.

We report the identification of six patients with 3q29 microdeletion syndrome. The clinical phenotype is variable despite an almost identical deletion size. The phenotype includes mild-to-moderate mental retardation, with only slightly dysmorphic facial features that are similar in most patients: a long and narrow face, short philtrum, and high nasal bridge. Autism, gait ataxia, chest-wall deformity, and long and tapering fingers were noted in at least two of six patients. Additional features--including microcephaly, cleft lip and palate, horseshoe kidney and hypospadias, ligamentous laxity, recurrent middle ear infections, and abnormal pigmentation--were observed, but each feature was only found once, in a single patient. The microdeletion is approximately 1.5 Mb in length, with molecular boundaries mapping within the same or adjacent bacterial artificial chromosome (BAC) clones at either end of the deletion in all patients. The deletion encompasses 22 genes, including PAK2 and DLG1, which are autosomal homologues of two known X-linked mental retardation genes, PAK3 and DLG3. The presence of two nearly identical low-copy repeat sequences in BAC clones on each side of the deletion breakpoint suggests that nonallelic homologous recombination is the likely mechanism of disease causation in this syndrome.

This paper reports on the use of a high-throughput diagnostic genetic screening for coagulation, platelet, or thrombotic disorders in a series of more than 2000 patients.

Stickler syndrome is a dominantly inherited disorder affecting the fibrillar type II/XI collagen molecules expressed in vitreous and cartilage. Mutations have been found in COL2A1, COL11A1 and COL11A2. It has a highly variable phenotype that can include midline clefting, hearing loss, premature osteoarthritis, congenital high myopia and blindness through retinal detachment. Although the systemic phenotype is highly variable, the vitreous phenotype has been used successfully to differentiate between patients with mutations in these different genes. Mutations in COL2A1 usually result in a congenital membranous vitreous anomaly. In contrast mutations in COL11A1 result in a different vitreous phenotype where the lamellae have an irregular and beaded appearance. However, it is now apparent that a new sub-group of COL2A1 mutations is emerging that result in a different phenotype with a hypoplastic vitreous that fills the posterior chamber of the eye, and is either optically empty or has sparse irregular lamellae. Here we characterise a further 89 families with Stickler syndrome or a type II collagenopathy, and correlate the mutations with the vitreous phenotype. We have identified 57 novel mutations including missense changes in both COL2A1 and COL11A1 and have also detected two cases of complete COL2A1 gene deletions using MLPA.