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

Research output: Contribution to journalArticlepeer-review

  • Authors:
  • Lionel Willatt
  • James Cox
  • John Barber
  • Elisabet Dachs Cabanas
  • Amanda Collins
  • And 14 others
  • External authors:
  • Dian Donnai
  • David R. FitzPatrick
  • Eddy Maher
  • Howard Martin
  • Josep Parnau
  • Lesley Pindar
  • Jacqueline Ramsay
  • Charles Shaw-Smith
  • Erik A. Sistermans
  • Michael Tettenborn
  • Dorothy Trump
  • Bert B A De Vries
  • Kate Walker
  • F. Lucy Raymond

Abstract

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 ∼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. © 2005 by The American Society of Human Genetics. All rights reserved.

Bibliographical metadata

Original languageEnglish
Pages (from-to)154-160
Number of pages6
JournalAmerican Journal of Human Genetics
Volume77
Issue number1
DOIs
Publication statusPublished - Jul 2005