3q29 duplications

3q29 duplications have been associated with highly variable neurodevelopmental disorders ranging from mild to severe intellectual disability (ID), learning difficulties,

3q29 duplication

and associated clinical features such as cerebral, ocular or cardiac malformations. The impact of the 3q29 duplication remains unclear; thus, Massier et al. attempt to improve the genotype-phenotype by reporting a French cohort of 46 patients from 31 families with a 3q29 duplication identified by chromosomal microarray analysis. Their cohort included 23 patients (from 14 families) who has a “standard” 1.6 Mb duplication, 10 patients (from 8 families) with relatively large duplications (> 1.8 Mb) and 13 patients (from 9 families) with small duplications (<1 Mb). In all groups significant part of duplications was inherited from one of the parents. In the subgroup with large duplications six patients had additional imbalance mostly due to parental translocations. Several patients had additional imbalance unrelated to parental rearrangements. Focusing on those with “standard” 3q29 duplications without known additional genetic variation 16/19 exhibited developmental delay (DD), 9/16 exhibited learning disabilities, 3/16 with mild ID, and 4/14 with neuropsychiatric disorders such as autism and attention deficit hyperactivity disorder. Small duplications ranged from 129 kb to 810 kb in families. Patients without associated imbalance in this group revealed DD (3/9), ID (3/9), learning disability (3/9), neuropsychiatric disorder (6/9), and malformations (2/9). The authors report that whether in the current cohort or in the literature, morphological abnormalities are described in very low and variable proportions. They also considered the genes encompassed in the smaller than 1 Mb duplications, such as BDH1 and DLG1, but were unable to provide evidence to support a possible critical region. They ultimately summarize that overlapping or recurrent ~1.6 Mb 3q29 duplication could lead to a mild neurodevelopmental phenotype with variable expressivity and incomplete penetrance. The authors suggest that there is a need for further genetic investigation of individuals who present with a more severe phenotype.

Massier et al. “3q29 duplications: A cohort of 46 patients and a literature review”. “American Journal of Medical Genetics Part A” 2024, v. 194(7), e63531.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact info@chromodisorder.org