Spectrum of MECP2 gene mutations in a cohort of Indian patients with Rett syndrome: Report of two novel mutations

Das, Dhanjit Kumar; Raha, Sarbani; Sanghavi, Daksha; Maitra, Anurupa; Udani, Vrajesh

doi:10.1016/j.gene.2012.11.024

Cited by 17 publications

(15 citation statements)

References 22 publications

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“…Esta evidencia sugiere que es importante utilizar MLPA en los casos en que no se han encontrado variantes puntuales en el gen MECP2. Un 87% de las variantes patogénicas encontradas están ubicadas en los dominios MBD y TRD, en los exones 3 y 4, tal como ha sido descrito en estudios previos [22][23] .…”

Section: Discussionunclassified

Síndrome de Rett: análisis molecular del gen MECP2 en pacientes chilenas

2019

Rev Chil Pediatr

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Introducción: El síndrome de Rett (RTT) es un trastorno neurológico progresivo caracterizado por producir una regresión del desarrollo psicomotor en niñas previamente sanas. La mayoría de los casos son causados por variantes patogénicas en el gen MECP2, que codifica para la proteína methyl CpGbinding protein 2.Objetivo: Describir la frecuencia y el tipo de variantes patogénicas en MECP2 en mujeres chilenas con diagnóstico clínico de RTT.Pacientes y Método: Se invitó a participar en este estudio a mujeres chilenas con sospecha clínica de RTT. Se reunió información clínica mediante un cuestionario. Se analizaron variantes patogénicas en MECP2 mediante el método de secuenciación de Sanger y se utilizó Multiple Ligation-dependant Probe Amplification (MLPA) para la detección de duplicaciones y deleciones.Resultado: El estudio incluyó 14 pacientes con sospecha de RTT, de las cuales 8 (57%) pacientes tuvieron variantes patogénicas. Las restantes permanecen sin diagnóstico molecular.Conclusión: Variantes patogénicas en MECP2 están presentes en pacientes chilenas con RTT. Es probable que haya otros genes o diagnósticos involucrados en las pacientes sin hallazgos en MECP2. A partir de este trabajo, el diagnóstico molecular está disponible en Chile.

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Section: Discussionunclassified

Síndrome de Rett: análisis molecular del gen MECP2 en pacientes chilenas

2019

Rev Chil Pediatr

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“…TRD may also make direct contacts with basal transcription machinery, such as TFIIB, leading to repression in a diacetylase‐independent manner (Yu, Thiesen, & Strätling, ). The majority of mutations identified in RTT patients were located within the MBD domain or TRD domain (Das, Raha, Sanghavi, Maitra, & Udani, ; Weaving et al., ). Nevertheless, other mutations were also identified in the C‐terminal of MECP2 in RTT patients (Hite et al., ; Shahbazian & Zoghbi, ).…”

Section: Discussionmentioning

confidence: 99%

Zebrafish (Danio rerio , Hamilton-Buchanan, 1822) as a model to study bone diseases associated with Rett syndrome

2018

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Summary Rett syndrome (RTT) is a severe neurological disorder in humans that almost exclusively affects only females. This disease is characterized by an apparent normal growth and intellectual development during the first year of life, followed by a progressive regression in development characterized by loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability. Mutations in the X‐linked gene methyl‐CpG‐binding protein 2 (MECP2) were described in RTT patients. Several bone diseases related with decreased bone mass starting early in life were recently ascribed to RTT. Because the zebrafish was largely validated as a model for human genetic diseases, the main objective of this work was to investigate whether zebrafish could be a good model to study bone diseases associated with RTT. For this purpose, first compared were zebrafish and human MECP2 regarding their chromosomal environment, gene structure, and protein conservation. In silico analysis showed a similar genetic structure for zebrafish mecp2 and its human ortholog, and both species present spliced isoforms. Zebrafish and human MECP2 promoter regions present similar putative binding sites for known transcription factors that affect both neural and bone metabolisms. Protein bioinformatic analysis showed a high degree of conservation between zebrafish and human, particularly in the functional domains of both proteins. In conclusion, this study demonstrates that the zebrafish has the appropriate genetic characteristics for further consideration as a model to investigate the bone diseases associated with Rett syndrome.

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“…We have reported the spectrum of mutations in MECP2 (Das et al, 2013b) and CDKL5 (Das et al, 2013a) genes in large cohorts of individuals suffering from typical and variant forms of RTT. Here, we report the molecular screening of the FOXG1 gene in a cohort of 34 female patients with atypical and classic forms including early congenital variant of RTT.…”

Section: Introductionmentioning

confidence: 99%