ClinVar Genomic variation as it relates to human health

The terminal 1pterp36.32 deletion involves multiple protein coding genes, including DVL1 (OMIM 601365) and GABRD (OMIM 137163), and is expected to cause phenotypic and/or developmental abnormalities. Deletions of this locus have been associated with chromosome 1p36 deletion syndrome (OMIM 607872), which causes multiple congenital anomalies and intellectual disability (Shapira et al., Am. J. Hum. Genet. 61: 642-650, 1997. PMID: 9326330). There is little correlation between the deletion size and the number of clinical features present, although the severity may correlate with the deletion size (Shiba, et al., Acta Neuropathol Commun. 2013 Aug 2;1(1):45. PMID: 24252393). It has been suggested that some features of monosomy 1p36 might result from positional effects rather than a simple contiguous gene deletion (Redon et al., J Med Genet. 2005 Feb;42(2):166-71. PMID: 15689456). Nevertheless, candidate genes have been suggested, including DVL1 for the developmental delay phenotype, GABRD for the epilepsy phenotype, and PRKCZ for the cardiac abnormalities, all of which are involved in the current deletion (Collu et al., Am J Med Genet A. 2016 Jul;170(7):1889-94. PMID: 27144803; D'Angelo et al., Am J Med Genet A. 2010 Jan;152A(1):102-10. PMID: 20034100; Shimada et al., Brain Dev. 2015 May;37(5):515-26. PMID: 25172301). Furthermore, heterozygous pathogenic sequence variants including loss-of-function variants of DVL1 have been associated with autosomal dominant Robinow syndrome-2 (OMIM 616331), which is a rare skeletal dysplasia. This large deletion also includes a few additional genes that are associated with autosomal dominant OMIM phenotype: SKI (OMIM 182212), GABRD (OMIM 613060), GNB1(OMIM 616973), TMEM240 (OMIM 607454), and ATAD3A (OMIM 617183).