ClinVar Genomic variation as it relates to human health

The copy number loss of 3q27.1q28 involves 33 protein-coding genes, including multiple genes associated with autosomal dominant disorders: EHHADH (OMIM 607037), IGF2BP2 (OMIM 608289), CRYGS (OMIM 123730), DNAJB11 (OMIM 611341), HRG (OMIM 142640), KNG1 (OMIM 612358), and LPP (OMIM 600700). Interstitial deletions of 3q27.3 and 3q26.33q27.3 overlapping this region have been associated with emerging syndromes sharing common features such as growth retardation, developmental delay/intellectual disability, and facial dysmorphism (Jewell 2017, Castori 2015, Bouman 2015, Thevenon 2014, Mandrile 2013). Two small regions of overlap (SRO) were defined the3q27.3 region, both of which are fully encompassed in the current loss interval: SRO1 was associated with facial dysmorphism and psychosis, while SRO2 was common among those with low body mass index and a marfanoid habitus (Thevenon 2014). On the other hand, the proposed SRO for 3q26.33q27.3 deletions is more proximal and only partially overlaps the current interval (Bouman 2015). Compared to 3q27.3 deletions, the phenotype of 3q26.33q27.3 deletions is associated with more severe growth restriction (including microcephaly) and brain structural abnormalities. Thus, based onreview of the literature and gene content, the classification of this copy number variant (CNV) is likely pathogenic. References :Bouman et al. An interstitial de-novo microdeletion of 3q26.33q27.3 causing severe intrauterine growth retardation. Clin Dysmorphol. 2015Apr;24(2):68-74. PMID: 25714561.C astori et al. An additional patient with 3q27.3 microdeletion syndrome. J Child Neurol. 2015 Mar;30(4):500-4. PMID: 25038125. Jewell et al. 3q27.3 Microdeletion syndrome: further delineation of the second region of overlap and atopic dermatitis as a phenotypic feature. Clin Dysmorphol. 2017 Jul;26(3):154-156. PMID: 28288024. Mandrile et al. 3q26.33-3q27.2 microdeletion: a new microdeletion syndrome? Eur J Med Genet. 2013 Apr;56(4):216-21. PMID: 23357683. Thevenon et al. 3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus,intellectual disability and psychosis with mood disorder. J Med Genet. 2014 Jan;51(1):21-7. PMID: 24133203.