Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001033709 | SCV001197016 | pathogenic | Severe neonatal-onset encephalopathy with microcephaly | 2019-03-27 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing the full coding sequence of the MECP2 gene. The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this event is unknown, it may be in tandem or it may be located elsewhere in the genome. This variant has been observed to segregate with X-linked mental retardation in families (PMID: 24458799, 17088400). Additionally MECP2 is included in the critical region that is found in recurrent duplications of varying size that span chromosomal band Xq28 (MECP2 duplication syndrome). Individuals who carry these duplications have a phenotype that includes infantile hypotonia, developmental delay, poor speech development, recurrent infections, and seizures (PMID: 26930212, 17172942, 22578097, 17088400). Experimental studies have shown that additional copies of the MECP2 gene can cause over-expression of MECP2 mRNA in lymphoblasts (PMID: 16080119, 15689435). This has been shown to lead to interferon suppression in helper T cells (PMID: 23220634) and increased oxidative stress (PMID: 26930212). Additionally a mouse model in which MECP2 was over-expressed showed a phenotype similar to that seen in patients with MECP2 duplication syndrome (PMID: 15351775). For these reasons, this variant has been classified as Pathogenic. |