Dataset Information

Unusual Characteristics and Variable Expressivity in a Brazilian Family with Cherubism.

ABSTRACT: Cherubism is a rare genetic condition characterized by a bone nonneoplastic disease. We aimed to report a 6-year-old girl with cherubism presenting similar cases in the maternal family. However, her mother and grandmother seemed to be asymptomatic. The patient had an enlarged and asymmetric jaw with multiple enlarged cervical lymph nodes that increased in size with time. Sanger sequencing revealed a heterozygous mutation in exon 9 of SH3BP2 not only in the patient but also in her mother. Thus, we observed a variable expression and a probably reduced penetrance within the family, as well as unusual characteristics of the patient (in this case, the asymmetrical involvement of the jaw).

SUBMITTER: Deconte D

PROVIDER: S-EPMC7853913 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Unusual Characteristics and Variable Expressivity in a Brazilian Family with Cherubism.

Deconte Desirée D Correia Elisa Pacheco Estima EPE Haubert Géssica G de Souza Vinicius V Correia Jamile Dutra JD Maahs Marcia Angelica Peter MAP Zen Paulo Ricardo Gazzola PRG Fiegenbaum Marilu M Rosa Rafael Fabiano Machado RFM

Journal of pediatric genetics 20200228 1

Cherubism is a rare genetic condition characterized by a bone nonneoplastic disease. We aimed to report a 6-year-old girl with cherubism presenting similar cases in the maternal family. However, her mother and grandmother seemed to be asymptomatic. The patient had an enlarged and asymmetric jaw with multiple enlarged cervical lymph nodes that increased in size with time. Sanger sequencing revealed a heterozygous mutation in exon 9 of <i>SH3BP2</i> not only in the patient but also in her mother. ...[more]

PMID: 33552642

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Project description:Fragile X syndrome (FXS), is an X-linked inherited genetic disease. FXS is the leading cause of inherited intellectual disability and autism in the world. Those affected are characterized by intellectual disability, language deficit, typical facies, and macroorchidism. Alterations in the FMR1 gene have been associated with FXS. The majority of people with this condition have an allele with an expansion of more than 200 repeats in a tract of CGGs within the 5' untranslated region, and this expansion is associated with a hypermethylated state of the gene promoter. FXS has incomplete penetrance and variable expressivity. Intellectual disability is present in 100% of males and 60% of females. Autism spectrum disorder symptoms appear in 50% to 60% of males and 20% of females. Other characteristics such as behavioral and physical alterations have significant variations in presentation frequency. The molecular causes of the variable phenotype in FXS patients are becoming clear: these causes are related to the FMR1 gene itself and to secondary, modifying gene effects. In FXS patients, size and methylation mosaicisms are common. Secondary to mosaicism, there is a variation in the quantity of FMR1 mRNA and the protein coded by the gene Fragile Mental Retardation Protein (FMRP). Potential modifier genes have also been proposed, with conflicting results. Characterizing patients according to CGG expansion, methylation status, concentration of mRNA and FMRP, and genotypification for possible modifier genes in a clinical setting offers an opportunity to identify predictors for treatment response evaluation. When intervention strategies become available to modulate the course of the disease they could be crucial for selecting patients and identifying the best therapeutic intervention. The purpose of this review is to present the information available about the molecular causes of the variability of the expression incomplete penetrance and variable expressivity in FXS and their potential clinical applications.

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Dataset Information

Unusual Characteristics and Variable Expressivity in a Brazilian Family with Cherubism.

Publications

Unusual Characteristics and Variable Expressivity in a Brazilian Family with Cherubism.

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