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Targeted gene(s)/phenotype under study

Chromosome 3q29 duplication (OMIM 611936); BDH1 (OMIM 603063)

Abstract

3q29 microduplication syndrome is a rare genetic condition resulted from a 1.6 Mb duplication on the long arm (q) of chromosome 3. These patients presented with health problems in the first year of life as feeding problems, low gain of weight, hypotonia and respiratory distress; developmental delay and learning disability, gastrointestinal problems, seizures, and social interaction defect. 3-Hydroxybutyrate Dehydrogenase 1 (BDH1) gene encodes a member of the short-chain dehydrogenase/reductase gene family. This protein forms a homotetrameric lipid-requiring enzyme of the mitochondrial membrane and has a specific requirement for phosphatidylcholine for optimal enzymatic activity. The encoded protein catalyzes the interconversion of acetoacetate and (R)-3-hydroxybutyrate, the two major ketone bodies produced during fatty acid catabolism. BDH1 has been implicated in aging and Alzheimer’s disease, and may be responsible for ketone body metabolism within the brain.

We have identified a 3q29 microduplication syndrome in a 9-year-old-male resulted from two microduplications including the genes XXYLT1, ACAP2, and BDH1. Psychomotor delay and Autism-Spectrum-Disorder were the main features. Minimal overlapping region with other cases reported in literature includes only the gene BDH1.

Published reports on 3q29 microduplication syndrome are limited; therefore, the aim of this study is to collect clinical data on additional patients with a 3q29 microduplication syndrome and to analyse the link between the genotype and the phenotype and to determine the minimal critical region. This will aid in expanding our current knowledge on this syndrome, on the genes responsible for this disease and delineating associated phenotypes. This study could add important informations about which genes are responsible for psychomotory neurodevelopmental delay.

Coordinating clinicians/researchers

Alessandra Ferrarini
Contact: alessandra.ferrarini@eoc.ch

Institution

Service of Medical Genetics,
Italian Hospital of Lugano and University of Lugano,
6900 Lugano, Switzerland (CH)

Specific requirements beyond clinical data and genotype data sharing

  • Re-analysis of DNA samples : no
  • Resampling of patients : no
  • Linked to a translational/basic research project? yes