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Gene: MECP2

Green List (high evidence)

Well established gene disease association. Severe. Including intellectual disability, onset from near birth.
Pathogenic variants in MECP2 gene cause Rett syndrome (RTT), a severe neurodevelopmental disorder that almost always occurs in females. Males with non-RTT variants in the MECP2 gene can demonstrate a wide variety of phenotypes, including X-linked syndromic intellectual developmental disorder-13, and Lubs-type X-linked syndromic intellectual developmental disorder. Males with RTT-associated MECP2 mutations have neonatal severe encephalopathy that is usually lethal.
Female obligate carriers of variants expected to cause RTT may have skewed X-inactivation, and experience minimal signs of the condition, but can produce offspring affected. Some obligate carriers with skewed x-inactivation may have mild features such as motor coordination problems, mild learning disability.

- Lubs-type X-linked syndromic intellectual developmental disorder (MRXSL) is caused by duplication or triplication of the MECP2 gene.

- Intellectual developmental disorder, X-linked syndromic 13: affected males have been found to have SNV in the MECP2 gene causing AA substitution e.g. E137G - PMID: 10986043. A140V - PMID: 11007980. Small 240bp deletion also reported: PMID 11807877

A large amount of information on variant spectrum and disease can be found in MIM entry: https://omim.org/entry/300005

Created: 7 Feb 2025, 3:40 a.m. | Last Modified: 7 Feb 2025, 3:40 a.m.

Panel Version: 1.1460

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Encephalopathy, neonatal severe MIM#300673; Intellectual developmental disorder, X-linked syndromic 13 MIM#300055; Intellectual developmental disorder, X-linked syndromic, Lubs type MIM#300260

Publications

• 11402105
• 10577905
• 11071498
• 16647997
• 10508514
• 31206249
• 10986043
• 11807877