3q29 microdeletion syndrome

3q29 microdeletion syndrome is a rare genetic disorder resulting from the deletion of a segment of chromosome 3. This syndrome was first described in 2005.[1][2]

3q29 microdeletion syndrome
Other names3qter deletion, Monosomy 3q29
Chromosome 3 is associated with this condition

Presentation

The clinical phenotype of 3q29 microdeletion syndrome is variable. Clinical features can include mild to moderate intellectual disability with mildly dysmorphic facial features (long and narrow face, short philtrum and a high nasal bridge). Of the 6 reported patients, additional features including autism, ataxia, chest-wall deformity and long, tapering fingers were found in at least two patients.[1] A review of 14 children with interstitial deletions of 3q29, found 11 who had the common recurrent 1.6Mb deletion and displayed intellectual disability and microcephaly.[3]

The variability of phenotype is underscored by the report on a 6 and 9/12-year-old male patient with a de novo chromosome 3q29 microdeletion identified by BAC array comparative genomic hybridization assay (aCGH), with accompanying normal 46,XY high-resolution chromosome analysis. The patient has language-based learning disabilities and behavioral features consistent with diagnoses of autism and attention deficit hyperactivity disorder (ADHD) of the inattentive type. He also displays some other features previously associated with chromosome 3q29 microdeletion such as an elongated face, long fingers, and joint laxity. Most notably the patient, per formal IQ testing, did not have an intellectual disability. The patient demonstrated an average full-scale IQ result. This is notable because previously reported patients with chromosome 3q29 terminal deletion had intellectual disabilities. This report further expands the phenotypic spectrum to include the possibility of normal intelligence as corroborated by formal, longitudinal psycho-educational testing.[4]

The presence of two homologous low copy repeats either side of the deletion break-point suggests that non-allelic homologous recombination is the likely mechanism underlying this syndrome.

Genetics

The microdeletion, around 1.6 million base pairs, in length and encompasses 5 known genes and 17 uncharacterised transcripts. These include transferrin receptor, choline-phosphate cytidylyltransferase A, RNF168, serine/threonine-protein kinase, nuclear cap-binding protein complex, melanotransferrin, DLG1 and D-beta-hydroxybutyrate dehydrogenase

Research

Research on the risk for developing schizophrenia in Ashkenazi Jews and other populations showed that 3q29 microdeletion syndrome leads to a significant higher rate of schizophrenia.[5] In addition, a deletion at 3q29 was found to confer an increase to the odds of developing schizophrenia in a study of copy number variants and their effect on that disorder.[6]

References
  1. Willatt L, Cox J, Barber J, et al. (July 2005). "3q29 Microdeletion Syndrome: Clinical and Molecular Characterization of a New Syndrome". Am. J. Hum. Genet. 77 (1): 154–60. doi:10.1086/431653. PMC 1226188. PMID 15918153.
  2. Koochek M (2006). "Clinical and molecular characterization of a new syndrome: the case of 3q29 microdeletion syndrome". Clin. Genet. 69 (2): 121–3. doi:10.1111/j.1399-0004.2006.00570c.x. S2CID 85261528. Archived from the original on 2013-01-05.
  3. Ballif BC, Theisen A, Coppinger J, Gowans GC, Hersh JH, Madan-Khetarpal S, Schmidt KR, Tervo R, Escobar LF, Friedrich CA, McDonald M, Campbell L, Ming JE, Zackai EH, Bejjani BA, Shaffer LG (2008). "Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication". Mol Cytogenet. 1: 8. doi:10.1186/1755-8166-1-8. PMC 2408925. PMID 18471269.
  4. Cobb W, Anderson A, Turner C, Hoffman RD, Schonberg S, Levin SW (2010). "1.3 Mb de novo deletion in chromosome band 3q29 associated with normal intelligence in a child". Eur J Med Genet. 53 (6): 415–8. doi:10.1016/j.ejmg.2010.08.009. PMID 20832509.
  5. Mulle JG, Dodd AF, McGrath JA, Wolyniec PS, Mitchell AA, Shetty AC, Sobreira NL, Valle D, Rudd MK, Satten G, Cutler DJ, Pulver AE, Warren ST (August 2010). "Microdeletions of 3q29 confer high risk for schizophrenia". Am. J. Hum. Genet. 87 (2): 229–36. doi:10.1016/j.ajhg.2010.07.013. PMC 2917706. PMID 20691406.
  6. Rees E, Walters JT, Georgieva L, Isles AR, Chambert KD, Richards AL, Mahoney-Davies G, Legge SE, Moran JL, McCarroll SA, O'Donovan MC, Owen MJ, Kirov G (February 2014). "Analysis of copy number variations at 15 schizophrenia-associated loci". Br J Psychiatry. 204 (2): 108–14. doi:10.1192/bjp.bp.113.131052. PMC 3909838. PMID 24311552.
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