ClinVar Genomic variation as it relates to human health

The copy number loss of 1p34.3 involves 26 protein-coding genes, including all of AGO1 (OMIM 606228), AGO3 (OMIM 607355), and the entire GRIK3 gene except exon 1 (NM_000831.4, OMIM 138243). While rare, de novo interstitial hemizygous deletions of 1p34.3p34.2 have been reported in multiple unrelated patients with a variety of phenotypic findings such as developmental delay, hypotonia, facial dysmorphisms, and mild microcephaly. Especially, patients with deletions similar to or smaller than the current interval share phenotypes including early feeding problems, developmental delay, and hypotonia. Haploinsufficiency of AGO1 and AGO3 or GRIK3 has been suggested to contribute to the observed neurocognitive deficits (Dagklis 2016, Tokita 2015, Takenouchi 2014). Further, there are no similar copy number losses of this region in the general populations of the Database of Genomic Variants. Additional information of this deletion: this interval contains five genes that are associated with autosomal dominant disorders in OMIM, including GJB4 (OMIM 605425), GJB3 (OMIM 603324), NCDN (OMIM 608458), COL8A2 (OMIM 120252), and CSF3R (OMIM 138971), and three genes that are associated with autosomal recessive disorders, including GJB3, CSF3R, and ADPRS (OMIM 610624). References: Dagklis et al., Mol Cytogenet. 2016 Oct 6;9:77. PMID: 27713767. Takenouchi et al., Am J Med Genet A. 2014 Feb;164A(2):456-60. PMID: 24449200. Tokita et al., Eur J Hum Genet. 2015 Jun;23(6):761-5. PMID: 25271087.