Somatic mosaicism for Y120X mutation in the MECP2 gene causes atypical Rett syndrome in a male

Pieras, Juan Ignacio; Muñoz-Cabello, Beatriz; Borrego, Salud; Marcos, Irene; Sánchez, Javier; Madruga, Marcos; Antiñolo, Guillermo

doi:10.1016/j.braindev.2010.09.012

Cited by 23 publications

(23 citation statements)

References 9 publications

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“…The example of SCN1A above demonstrates that de novo mutations may be present in some cells of a parent of an affected individual (yet not detected in parental blood) or may arise post-zygotically during development of the affected individual (somatic mutation). Similarly, de novo mutations in the X-linked methyl CpG binding protein 2 ( MECP2 ) gene cause Rett syndrome, an ASD that is dominant in females and typically pre-natally lethal in males (75); mosaic mutations have been reported in males with both classic and atypical forms of Rett syndrome (76, 77). …”

Section: Other Neurological Diseases Attributable To Somatic Mutation?mentioning

confidence: 99%

Somatic Mutation, Genomic Variation, and Neurological Disease

Poduri

Evrony

Cai

et al. 2013

Science

527

446

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Genetic mutations causing human disease are conventionally thought to be inherited through the germ line from one’s parents and present in all somatic (body) cells, except for most cancer mutations, which arise somatically. Increasingly, somatic mutations are being identified in diseases other than cancer, including neurodevelopmental diseases. Somatic mutations can arise during the course of prenatal brain development and cause neurological disease—even when present at low levels of mosaicism, for example—resulting in brain malformations associated with epilepsy and intellectual disability. Novel, highly sensitive technologies will allow more accurate evaluation of somatic mutations in neurodevelopmental disorders and during normal brain development.

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Section: Other Neurological Diseases Attributable To Somatic Mutation?mentioning

confidence: 99%

Somatic Mutation, Genomic Variation, and Neurological Disease

Poduri

Evrony

Cai

et al. 2013

Science

527

446

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“…To the best of our knowledge, female MECP2 mosaic mutations have not been described in the literature. Male individuals carrying causative MECP2 mutations in a mosaic form have typical or mild/atypical RS, which is considerably milder than male carriers of the corresponding full mutations, who rarely survive to birth . Extrapolating on female mosaics, one would theoretically expect a mild RS or a status of almost asymptomatic carrier.…”

Section: Discussionmentioning

confidence: 99%

“…In a more recent report, a male with classic RS was described to carry a 5 bp duplication in the open reading frame of exonh1 of MECP2 , thus highlighting the importance of considering RS in males, as well as in females . In case of somatic MECP2 mosaicism, male patients can survive to birth and exhibit clinical features similar to the female full mutation or an atypical RS phenotype . The frequency of MECP2 mosaicism is currently unknown, with only male mosaic patient being reported so far and to our knowledge, no reports have been published to date describing MECP2 mutation mosaicism in females.…”

Section: Introductionmentioning

confidence: 99%

De novo mosaic MECP2 mutation in a female with Rett syndrome

Alexandrou

Papaevripidou

Alexandrou

et al. 2019

Clinical Case Reports

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Key Clinical Message We describe a female with Rett syndrome carrying a rare de novo mosaic nonsense mutation on MECP 2 gene, with random X‐chromosome inactivation. Rett syndrome severity in females depends on mosaicism level and tissue specificity, X‐chromosome inactivation, epigenetics and environment. Rett syndrome should be considered in both males and females.

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“…In this study, we first demonstrated that the weak peak in sequencing graph might represent a somatic mosaicism variant when screening the genotypes of the polymorphism variations in the 5′‐UTR of the hOGG1 gene. In reported studies on the screening of disease‐associated gene mutations, the mosaicism of the disease‐causing mutation was mostly identified by one or two methods, such as Sanger sequencing of the PCR products and/or pyrosequcing . We used four analytical methods (direct sequencing of PCR products, cloning and sequence analysis, pyrosequencing and artificial mosaicism model) to confirm the somatic mosaicism of the target SNPs progressively.…”

Section: Discussionmentioning

confidence: 99%

Detection of mosaicism for the polymorphic variants in the 5′‐UTR of hOGG1 by cloning and sequence analysis and pyrosequencing

Cao¹,

Li²,

Zhu³

et al. 2013

Electrophoresis

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Mosaicism refers to the presence of genetically distinct cell lines within an organism or a tissue. Somatic mosaicism exists in distinct populations of somatic cells and commonly arises as a result of somatic mutations, mainly in early embryonic development. SNPs are important markers that distinguish between different individuals in heterogeneous biological samples and contribute greatly to disease risk association studies. In this work, we investigated the relationship between the functional variants in the 5'-UTR of the hOGG1 gene and the risk of type 2 diabetes. Upon detection of the polymorphisms c.-53G>C, c.-23A>G, and c.-18G>T in the hOGG1 gene, we found that mosaicism was present in 3/28 (10.71%), 7/51 (13.73%), and 1/44 (2.27%) patients respectively, who were carriers of these single nucleotide variations, by cloning and sequence analysis and pyrosequencing. Statistical analysis showed that the frequency of the variation c.-23A>G in the hOGG1 5'-UTR in type 2 diabetic patients was significantly higher than that in healthy controls. However, sequencing of the mutant alleles in mosaic individuals showed weak peaks that may affect detection of the SNPs and impair association-based investigations.

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Somatic mosaicism for Y120X mutation in the MECP2 gene causes atypical Rett syndrome in a male

Cited by 23 publications

References 9 publications

Somatic Mutation, Genomic Variation, and Neurological Disease

Somatic Mutation, Genomic Variation, and Neurological Disease

De novo mosaic MECP2 mutation in a female with Rett syndrome

Detection of mosaicism for the polymorphic variants in the 5′‐UTR of hOGG1 by cloning and sequence analysis and pyrosequencing

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