Description
The copy number loss of 1q31.1q32.1 involves multiple protein-coding genes, including KCNT2 (OMIM 610044) and CDC73 (OMIM 607393). A similar 9.5 Mb deletion at this region, arising de novo, was reported in an individual with intellectual disability, obesity, and dysmorphic features (Hyder et al., Clin Dysmorphol. 2019 Jul;28(3):131-136. PMID: 31045593). Milani et al. also reported a larger de novo deletion of 1q31.1q32.1 in an individual with developmental delay, hyperactivity and behavioral disorder, and dysmorphic features including laterally sparse eyebrows, downslanting palpebral fissures, broad nasal root, long philtrum, thin upper lip and thick lower lip (Milani D, et al. Cytogenet Genome Res. 2012;136(3):167-70. PMID: 22398643). Furthermore, heterozygous pathogenic loss-of-function variants of CDC73 have been associated with autosomal dominant hyperparathyroidism-jaw tumor syndrome (aka parathyroid adenoma with cystic changes; OMIM 145001) and familial primary hyperparathyroidism (OMIM 145000). This large deletion also includes a few genes associated with autosomal dominant OMIM phenotypes: KCNT2 (OMIM 610044), CFH (OMIM 134370), CFHR3 (OMIM 605336), CFHR1 (OMIM 134371), CFHR5 (OMIM 608593), and CRB1 (OMIM 604210). There are no full copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, based on literature review and gene content, this copy number loss is interpreted as likely pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | unknown | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
