Case Report: Complicated Molecular Diagnosis of MECP2 Gene Structural Rearrangement in a Proband with Rett Syndrome

Excerpt

Rett syndrome (RTT, MIM 312750) (https://​www.​omim.​org) is a progressive X-linked dominant neurodevelopmental disorder affecting predominantly girls. Some cases of RTT in males were also described (Schwartzman et al. 1999, Clayton-Smith et al. 2000). It is characterized by arrested development after 6–18 months of age, regression of acquired skills, loss of speech, stereotypic hand movements, microcephaly, seizures, and mental retardation (Rett 1966). Its prevalence is estimated to be 1 per 10,000–15,000 newborn girls (Hagberg 1985). RTT cases are usually sporadic, caused by de novo mutations (Amir and Zoghbi 2000) in the MECP2 gene (MIM 300005). It is located on the long arm of the chromosome X at Xq28 locus and codes methyl-CpG-binding protein 2, which has pleiotropic effects on target genes and is required for neuron maturation and normal function of nerve cells (Amir et al. 1999; Banerjee et al. 2019). Point mutations and gross deletions in the MECP2 gene, as well as complex chromosome X structural rearrangements affecting this gene, were described (Krishnaraj et al. 2017). …