The array of clinical phenotypes of males with mutations in <i>Methyl‐CpG binding protein 2</i>

Neul, Jeffrey L.; Benke, Timothy A.; Marsh, Eric D.; Skinner, Steven A.; Merritt, Jonathan K; Lieberman, David N.; Standridge, Shannon; Feyma, Tim; Heydemann, Peter; Peters, Sarika U.; Ryther, Robin; Jones, Mary; Suter, Bernhard; Kaufmann, Walter E.; Glaze, Daniel G.; Percy, Alan K.

doi:10.1002/ajmg.b.32707

Cited by 64 publications

(57 citation statements)

References 48 publications

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“…Eight male patients with MECP2 mutations were identified in this study, including two diagnosed with typical RTT, three with atypical RTT, and three with ID/DD. Previous studies have demonstrated various clinical phenotypes in males with MECP2 mutations, ranging from cognitive impairment to neonatal encephalopathy 32,33 . However, male patients in this study presented with a milder phenotype than most of the previously reported patients, and there were no such cases of encephalopathy reported in the current study.…”

Section: Discussioncontrasting

confidence: 74%

“…Male individuals with MECP2 mutations have actually been rarely reported worldwide, only about 100 males with MECP2 mutations have been reported 10,32 . Eight male patients with MECP2 mutations were identified in this study, including two diagnosed with typical RTT, three with atypical RTT, and three with ID/DD.…”

Section: Discussionmentioning

confidence: 94%

“…One of the possible reasons is that such encephalopathy aggravated too quickly to present at the outpatient clinic. Neul et al 32 reported 14 of 28 male patients met the criteria for atypical RTT, but presented with more delayed development, ventilator requirement, and early death, and they termed this phenotype as “male RTT encephalopathy”. However, the five male RTT patients in this study presented with a milder phenotype, none of them with severe manifestations like respiratory support or early death.…”

Section: Discussionmentioning

confidence: 99%

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MECP2 mutation spectrum and its clinical characteristics in a Chinese cohort

et al. 2020

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The dysfunction of methyl‐CpG‐binding protein 2 (MeCP2) is associated with several neurological disorders, of which Rett syndrome (RTT) is the most prominent. This study focused on a Chinese patient cohort with MECP2 mutations, and analyzed the characteristics of these mutations and their clinical manifestations. In total, 666 patients were identified with 126 different MECP2 mutations, including 22 novel mutations. Over 80% of patients carried an MECP2 mutation on exon 4. Nonsense and missense mutations were the most commonly reported types. Missense mutations were mainly located on methyl‐CpG‐binding domain (MBD), and nonsense mutations predominantly occurred on transcription repression domain (TRD) and inter domain. The predilection site of large deletion was exon 3 and/or exon 4. Patients with p.R133C, p.R294*, p.R306C, and C‐terminal domain (CTD) deletions were less severely affected. Significant differences were found in ambulation ability, hand function, and language among different mutation groups. Three female patients with MECP2 mutations (1 with p.R306P and 2 with p.R309W) only presented with intellectual disability/developmental delay (ID/DD), and no obvious RTT symptoms were reported. Eight male individuals with MECP2 mutations were also identified in this study, including 2 diagnosed with typical RTT, 3 with atypical RTT and 3 with ID/DD.

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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MECP2 mutation spectrum and its clinical characteristics in a Chinese cohort

et al. 2020

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“…Mutations of methyl‐CpG binding protein 2 ( MECP2 ) on the X chromosome are identified in over 90% of patients with a typical RTT phenotype. MECP2 mutations were mainly identified in females with RTT and Rett‐like syndrome (RTT‐l), while males with MECP2 mutations mainly present with severe encephalopathy and fulfil the criteria of variant RTT as they develop (Neul et al, 2018; Soffer and Sidlow, 2016; Tokaji et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Surface‐ and voxel‐based brain morphologic study in Rett and Rett‐like syndrome with MECP2 mutation

Shiohama

Levman

Takahashi

2019

Intl J of Devlp Neuroscience

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Rett syndrome (RTT) is a rare congenital disorder which in most cases (95%) is caused by methyl‐CpG binding protein 2 (MECP2) mutations. RTT is characterized by regression in global development, epilepsy, autistic features, acquired microcephaly, habitual hand clapping, loss of purposeful hand skills, and autonomic dysfunctions. Although the literature has demonstrated decreased volumes of the cerebrum, cerebellum, and the caudate nucleus in RTT patients, surface‐based brain morphology including cortical thickness and cortical gyrification analyses are lacking in RTT. We present quantitative surface‐ and voxel‐based morphological measurements in young children with RTT and Rett‐like syndrome (RTT‐l) with MECP2 mutations. The 8 structural T1‐weighted MR images were obtained from 7 female patients with MECP2 mutations (3 classic RTT, 2 variant RTT, and 2 RTT‐l) (mean age 5.2 [standard deviation 3.3] years old). Our analyses demonstrated decreased total volumes of the cerebellum in RTT/RTT‐l compared to gender‐ and age‐matched controls (t (22)=‐2.93, p = .008, Cohen's d = 1.27). In contrast, global cerebral cortical surface areas, global/regional cortical thicknesses, the degree of global gyrification, and global/regional gray and white matter volumes were not statistically significantly different between the two groups. Our findings, as well as literature findings, suggest that early brain abnormalities associated with RTT/RTT‐l (with MECP2 mutations) can be detected as regionally decreased cerebellar volumes. Decreased cerebellar volume may be helpful for understanding the etiology of RTT/RTT‐l.

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“…Rett syndrome is a rare disease, yet with 1 in 10-12,000 females [104][105][106][107], and fewer males [108][109][110][111], considered to have the disease, the number globally is not insubstantial. This thesis predominantly addresses issues related to the communications challenges, support needs and (hidden) potential of individuals with Rett syndrome.…”

Section: Relevancementioning

confidence: 99%

Rett Syndrome

Townend¹

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People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. Rett Syndrome as a Rare Disease With a reported incidence of 1 in 10,000-12,000 females, Rett syndrome is classified as a rare disease for good reason. At the present time, around 7,000 rare diseases have been identified, affecting some 300-350 million people globally [63]. However, the exact number is difficult to quantify as definitions of 'rare disease' vary. In Europe a disease is said to be rare if it affects fewer than 1 in 2,000 people and in the US, according to the US Rare Diseases Act of 2002, if it affects fewer than 200,000 Americans at any one time [64]. Around 30 million people are estimated to be living with a rare disease in the European Union (6-8% of the population) [65] and 25-30 million in the US [66]; approximately 80% of rare diseases are genetic in origin [67]. According to the NGO Committee for Rare Diseases 4 , the challenges for people living with rare disease can be attributed to the following factors: • "Patients and experts are few and geographically scattered • Little information about the diseases, knowledge and good practices are limited 2 Low-tech AAC = a system that is not electronic and does not require a power source e.g. individual objects, photos, communication board/ book. 3 High-tech AAC = an electronic device with speech output. The screen can have a static or a dynamic display and the output can be recorded/digitized speech or synthesized speech. High-tech systems range from single message devices to complex computer-based systems. 4 The NGO Committee for Rare Diseases (United Nations, New York) is a substantive committee established under the umbrella of the Conference of NGOs in Consultative Relationship with the United Nations. It was initiated by the Ågrenska Foundation and EURORDIS to bring increased political recognition to the challenges of rare diseases globally. It's inaugural meeting was held in New York in November 2016. Consequently, this is a field in public health and research that would certainly benefit from globally concerted action and international collaboration." [63 p....

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The array of clinical phenotypes of males with mutations in Methyl‐CpG binding protein 2

Cited by 64 publications

References 48 publications

MECP2 mutation spectrum and its clinical characteristics in a Chinese cohort

MECP2 mutation spectrum and its clinical characteristics in a Chinese cohort

Surface‐ and voxel‐based brain morphologic study in Rett and Rett‐like syndrome with MECP2 mutation

Rett Syndrome

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