Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2019) 7 P118 | DOI: 10.1530/boneabs.7.P118

ICCBH2019 Poster Presentations (1) (226 abstracts)

Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with bone disease severity in Rett syndrome

Carla Caffarelli 1 , Maria Dea Tomai Pitinca 1 , Valentina Francolini 1 , Roberto Canitano 2 , Claudio De felice 2 , Joussef Hayek 2 & Stefano Gonnelli 1

1Department of Medicine, Surgery and Neuroscience, of Siena, Siena, Italy; 2Paediatrics Neuropsychiatry Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Objective: Rett syndrome (RTT) is an X-linked neurodevelopment disorder. More than 95% of RTT female have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. Specific MECP2 mutations may lead phenotypic variability and different degrees of disease severity. It is known that low bone mass is a frequent complication of subjects with Rett syndrome. This study aimed to investigate if specific MECP2 mutations may affects the degree of involvement of the bone status in Rett subjects.

Methods: The study cohort consisted of a group of 227 well defined RTT females (aged 2–38 yrs). Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. In all subjects bone mineral density at whole body (BMD-WB) and at femur (BMD-FN and BMD-TH) were measured. QUS parameters were assessed at phalanxes (AD-SoS and BTT). Moreover, ambulation capacity, fracture history and presence of scoliosis were assessed.

Results: In agreement with literature data, we consider the most eight common point mutations: R106W N=3; R133C N=14; T158M N=27; R168X N=17; R255X N=16; R270X N=22; R294W N=10; R306C N=13. We divided the subjects with the most common point mutations in two group based on genotype-phenotype severity; in particular, there has been consensus in recognising that the mutations T158M, R168X, R255X, R270X are considered more severe. BMD-WB, BMD-FN and BMD-TH were lower in RTT subjects that present the most severe mutations with respect to less severe mutations, but the difference was statistically significant only for BMD-TH Z-score (−3.44±1.18 vs −1.75±1.99; P<0.05). Also both AD-SoS and BTT values were lower in subjects that present the most severe mutations but the difference was not statistically significant. Moreover, RTT females with more severe mutations present a higher prevalence of scoliosis (60.0% vs 36.7%; P<0.05) and of inability to walk (77.1% vs 51.7%; P<0.05).

Conclusion: This study confirms that MECP2 mutation type is a strong predictor of disease severity in Rett subjects. In particular, the subjects with more severe mutation present a greater deterioration of bone status, and a higher prevalence of scoliosis and inability to walk.

Disclosure: The authors declared no competing interests.

Volume 7

9th International Conference on Children's Bone Health


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