ClinVar

Description

The copy number loss of 15q21.3 involves several protein-coding genes and is expected to cause phenotypic and/or developmental abnormalities. It includes TCF12 (OMIM 600480) and multiple exons (NM_130810.4) of the 5' portion of DNAAF4 (OMIM 608706). Haploinsufficiency of TCF12 is associated with autosomal dominant craniosynostosis-3 (OMIM 615314), which is characterized by premature fusion of the cranial sutures leading to skull deformity and, in some cases, increased intracranial pressure. If left untreated, the increase in intracranial pressure can result in permanent neurodevelopmental disability. Affected individuals may also have mild dysmorphic facial features and limb anomalies. TCF12 pathogenic variants are frequently inherited from an unaffected parent and familial segregations with reduced penetrance have been reported (Sharma et al., Nat Genet 2013;45(3):304-7, PMID: 23354436). Additionally, heterozygous sequence variants of DNAAF4 are associated with autosomal dominant susceptibility to dyslexia-1 (OMIM 127700). There are two genes in this copy number loss that are associated with autosomal recessive disorders: DNAAF4 and MNS1 (OMIM 610766).