3q29 Microdeletion syndrome: Clinical and molecular characterization of a new syndrome

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 similar to 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.