ClinVar Genomic variation as it relates to human health

The Xq28 deletion is an approximately ~1.4 MB deletion at the terminal region of the long arm of the X-chromosome. The centromeric breakpoint of this deletion is within a LCR and is poorly mapped with genome sequencing technology. Microarray analysis suggests this deletion has centromeric breakpoint occurring between the L1 and L2 region at the Int22h1 border (see [PMID:29341460] and extending to the telomere of Xq, and does include the Pseudoautosomal Region 2 (PAR2) of the X chromosome. This region contains approximately 55 genes, 19 of which are OMIM associated. Several of these genes are associated with X-linked conditions including DKC1 (Dyskeratosis congenita X-Linked; MIM#305000), F8 (Hemophilia A; MIM#306700), RAB39B (Intellectual Disability, X-Linked 72; MIM#300271 and Waisman syndrome; MIM#311510), CLIC2 (?Intellectual Disability, X-Linked, syndromic 32; MIM#300886), and TMLHE ({Autism, susceptibility to, X-linked 6}; MIM#300872). Loss of each of these genes, or deletion in this region, is linked to disorders primarily affecting males, with females largely being asymptomatic. However, mildly affected females and phenotypic variability in females has also been rarely reported [PMID:27570172, 33082527, Family 6-PMID:25927380, others] and possibly corresponds to skewing of X-chromosome inactivation in those individuals. This variant was detected de novo in an individual submitted for clinical testing. The de novo Xq28 deletion is reported as Pathogenic.