The A140V mutation in the MECP2 gene is not a common etiological factor among Brazilian mentally retarded males

Santos, J. M.; Abdalla, Cláudia Bueno; Campos, Mário; Santos-Rebouças, Cíntia Barros; Pimentel, Márcia Mattos Gonçalves

doi:10.1016/j.neulet.2004.12.036

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…Even when males with MECP2 have some of the distinctive features of RTT, such as loss of spoken language, loss of hand skills, or hand stereotypies, these features may be significantly subtler than those seen in females with RTT, further limiting specific clinical identification. This notion is borne out by MECP2 mutation studies of groups with neurodevelopmental delay that revealed mutations in 1.3–1.7% of males [Orrico, A. et al 2000, Couvert, P. et al 2001, Moncla, A.et al 2002, Yntema, H. G.et al 2002, Yntema, H. G.et al 2002, Bourdon, V.et al 2003, Kammoun, F.et al 2004, dos Santos, J. M.et al 2005, Ylisaukko-Oja, T.et al 2005, Donzel-Javouhey, A.et al 2006, Moog, U.et al 2006, Tejada, M. I.et al 2006], whereas few of these individuals were suspected as having MECP2 mutations. We expect that as whole exome or genome sequencing becomes commonly used to characterize males with neurodevelopmental disorders, it is likely that the identification of MECP2 mutations in these males will increase.…”

Section: Discussionmentioning

confidence: 99%

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

Neul

Benke

Marsh

et al. 2018

American J of Med Genetics Pt B

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Mutations in the X-linked gene MECP2 are associated with a severe neurodevelopmental disorder, Rett syndrome, primarily in girls. It had been suspected that mutations in MECP2 led to embryonic lethality in males, however such males have been reported. To enhance understanding of the phenotypic spectrum present in these individuals, we identified thirty males with MECP2 mutations in the RTT Natural History Study databases. A wide phenotypic spectrum was observed, ranging from severe neonatal encephalopathy to cognitive impairment. Two males with a somatic mutation in MECP2 had classic RTT. Of the remaining 28 subjects, 16 had RTT-causing MECP2 mutations, 9 with mutations that are not seen in females with RTT but are likely pathogenic, and 3 with uncertain variants. Two subjects with RTT-causing mutations were previously diagnosed as having atypical RTT; however, careful review of the clinical history determined that an additional 12/28 subjects met criteria for atypical RTT, but with more severe clinical presentation and course, and less distinctive RTT features, than females with RTT, leading to the designation of a new diagnostic entity, Male RTT Encephalopathy. Increased awareness of the clinical spectrum and widespread comprehensive genomic testing in boys with neurodevelopmental problems will lead to improved identification.

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Section: Discussionmentioning

confidence: 99%

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

Neul

Benke

Marsh

et al. 2018

American J of Med Genetics Pt B

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“…The A140V variant, noted in the references above as well in subsequent publications, was initially described as causing developmental delay only in males. More recently, descriptions of neurologic or psychiatric manifestations have been seen in females with this variant as well [9,13,25,26].…”

Section: Opinionmentioning

confidence: 98%

“…As an X-linked dominant disorder, its occurrence solely in females was expected and the presence of MECP2 variants in males was initially regarded as lethal. Subsequently, numerous reports emerged in the decade after the gene discovery describing males with MECP2 variants and clinical features ranging from developmental delay to significant neonatal encephalopathy [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Yet, the notion that pre-term or early neonatal male lethality is likely has remained even to the present day [20], plus two reports from rettsyndromenews.…”

Section: Opinionmentioning

confidence: 99%

The continuing Conundrum regarding MECP2 variants in Males

Percy¹

2022

AJBSR

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“…312750) is an X-linked dominant neurodevelopmental disorder and is the second most common cause of mental retardation in females, following Down syndrome (Rett, 1966;dos Santos et al, 2005). The vast majority of cases of RTT (more than 99%) are sporadic occurrences and familial recurrences are rare (Hoffbuhr et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic mutational analysis of MECP2 in Korean patients with Rett syndrome

Kim

Kim²,

Son³

et al. 2006

Exp Mol Med

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Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting 1 per 10,000-15,000 female births worldwide. The disease-causing gene has been identified as MECP2 (methylCpG-binding protein 2). In this study, we performed diagnostic mutational analysis of the MECP2 gene in RTT patients. Four exons and a putative promoter of the MECP2 gene were analyzed from the peripheral blood of 43 Korean patients with Rett syndrome by PCR-RFLP and direct sequencing. Mutations were detected in the MECP2 gene in approximately 60.5% of patients (26 cases/43 cases). The mutations consisted of 14 different types, including 9 missense mutations, 4 nonsense mutations and 1 frameshift mutation. Of these, three mutations (G161E, T311M, p385fsX409) were newly identified and were determined to be disease-causing mutations by PCR-RFLP and direct sequencing analysis. Most of the mutations were located within MBD (42.3%) and TRD (50%). T158M, R270X, and R306C mutations were identified at a high frequency. Additionally, an intronic SNP (IVS3 + 23C＞G) was newly identified in three of the patients. IVS3 + 23C＞G may be a disease-related and Korea-specific SNP for RTT. L100V and A201V are apparently disease-causing mutations in Korean RTT, contrary to previous studies. Disease-causing mutations and polymorphisms are important tools for diagnosing RTT in Koreans. The experimental procedures used in this study should be considered for clinical molecular biologic diagnosis.

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The A140V mutation in the MECP2 gene is not a common etiological factor among Brazilian mentally retarded males

Cited by 5 publications

References 39 publications

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

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

The continuing Conundrum regarding MECP2 variants in Males

Diagnostic mutational analysis of MECP2 in Korean patients with Rett syndrome

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