Characterization of seven novel mutations on the HEXB gene in French Sandhoff patients

Gaignard, Pauline; Fagart, Jérôme; Niemir, Natalia; Puech, Jean-Philippe; Azouguene, Emilie; Dussau, Jeanne; Caillaud, Catherine

doi:10.1016/j.gene.2012.09.124

Cited by 21 publications

(21 citation statements)

References 25 publications

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“…E n l o s últimos años, se han publicado 39 casos de e300 / Arch Argent Pediatr 2017;115(5):e298-e301 / Presentación de casos clínicos pacientes con diversos orígenes étnicos, entre ellos, paquistaníes, japoneses, brasileros, italianos, españoles, franceses, canadienses y estadounidenses. 4,[8][9][10][11][12][13][14][15] En Argentina, si bien existe la población endogámica con alta incidencia de ES infantil, hasta ahora, ningún paciente había tenido diagnóstico de ES juvenil. 3,6,7 Maegawa y col., en 2006, publicaron una revisión de la historia natural de las gangliosidosis GM2 variante juvenil (enfermedades de TaySachs y Sandhoff) y analizaron 21 casos nuevos y 134 pacientes previamente descritos en la bibliografía.…”

Section: Discussionunclassified

“…La variante p.Y266D fue registrada en 5 enfermos, de los cuales 3 se correspondieron con la forma infantil de la enfermedad y 2 con la variante juvenil. 4,9,10 Además, el cambio p.R539C solo fue identificado en un paciente caucásico para el que no hay datos acerca de la edad de diagnóstico, forma clínica ni edad de fallecimiento. 10 No existen registros previos de pacientes argentinos que hayan presentado estas mutaciones.…”

Section: Discussionunclassified

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Variante juvenil de la enfermedad de Sandhoff: presentación del primer caso descrito en Argentina

Mugnaini

Pereyra²,

Kremer

et al. 2017

Arch Argent Pediat

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Section: Discussionunclassified

Variante juvenil de la enfermedad de Sandhoff: presentación del primer caso descrito en Argentina

Mugnaini

Pereyra²,

Kremer

et al. 2017

Arch Argent Pediat

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“…Interestingly, since our initial report of the c.115delG variant in northern Saskatchewan it has also been detected in France [31]. The c.115delG allele was paternally inherited by a French patient whose father was of Vietnamese descent [31].…”

Section: Discussionmentioning

confidence: 99%

“…The c.115delG allele was paternally inherited by a French patient whose father was of Vietnamese descent [31]. As part of future investigations it would be interesting to conduct haplotype analysis to determine the origin of the c.115delG variant.…”

Section: Discussionmentioning

confidence: 99%

Incidence and carrier frequency of Sandhoff disease in Saskatchewan determined using a novel substrate with detection by tandem mass spectrometry and molecular genetic analysis

Fitterer

Hall

Antonishyn

et al. 2014

Molecular Genetics and Metabolism

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Sandhoff disease is a rare progressive neurodegenerative genetic disorder with a high incidence among certain isolated communities and ethnic groups around the world. Previous reports have shown a high occurrence of Sandhoff disease in northern Saskatchewan. Newborn screening cards from northern Saskatchewan were retrospectively screened in order to investigate the incidence and determine the carrier frequency of Sandhoff disease in these communities. PCR-based screening was conducted for the c.115delG (p.(Val39fs)) variant in the HEXB gene that was previously found in 4 Sandhoff disease patients from this area. The carrier frequency for this allele was estimated to be ~1:27. MS/MS-based screening of hexosaminidase activity along with genetic sequencing allowed for the identification of additional variants based on low total hexosaminidase activity and high % hexosaminidase A activity relative to c.115delG carriers. In total 4 pathogenic variants were discovered in the population (c.115delG, c.619A>G, c.1601G>T, and c.1652G>A) of which two are previously unreported (c.1601G>T and c.1652G>A). The combined carrier frequency of these alleles in the study area was estimated at ~1:15. Based on the number of cases of Sandhoff disease from this area we estimate the incidence to be ~1:390 corresponding to a child being born with the disease every 1–2 years on average. The results from our study were then compared with variants in the HEXB gene from the genomes available from the 1000 Genomes project. A total of 19 HEXB variants were found in the 1092 genomes of which 5 are suspected of having a deleterious effect on hexosaminidase activity. The estimated carrier frequency of Sandhoff disease in Saskatchewan at 1:15 is more than 3 times higher than the carrier frequency in the global sample provided by the 1000 Genomes project at 1:57.

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“…The variant rs373979283 which entails the substitution Y266D was previously reported in patients with Sandoff disease (41)(42)(43), was predicted to be deleterious by all of the softwares used in this study in spite of the fact that Tyrosine is not highly conserved at this position because other homologous sequences were observed having other residues at the same position, but none of them is similar to Aspartate in terms of physiochemical properties, because Aspartate is smaller and less hydrophobic than Tyrosine, which could affect the protein folding process, in addition to that Tyrosine is neutral while Aspartate is negative in charge, therefore, this mutation could still be damaging.…”

Section: Disscutionmentioning

confidence: 92%

Comprehensive Analysis of HEXB Protein Reveal Forty Two Novel nsSNPs That May Lead to Sandhoff disease (SD) Using Bioinformatics

Ta¹,

Mm²,

Mustafa³

et al. 2019

Preprint

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Background: Single Nucleotide Polymorphisms (SNPs) in the HEXB gene are associated with a neurodegenerative disorder called Sandhoff disease (SD) (GM2 gangliosidosis-O variant). This study aimed to predict the possible pathogenic SNPs of this gene and their impact on the protein using different bioinformatics tools. Methods: SNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different algorithms collectively predicted the effect of single nucleotide substitution on both structure and function of beta subunit beta subunit of both hexosaminidase A and hexosaminidase B proteins. Results: Forty nine mutations were found to be extremely damaging to the structure and function of the HEXB gene protein.Conclusion: According to this study, forty two novel nsSNP in HEXB are predicted to have possible role in Sandhoff disease using different bioinformatics tools, beside two SNPs found to have effect on miRNAs binding site affecting expression of HEXB gene. Our findings may assist in genetic study and diagnosis of Sandhoff disease.

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Characterization of seven novel mutations on the HEXB gene in French Sandhoff patients

Cited by 21 publications

References 25 publications

Variante juvenil de la enfermedad de Sandhoff: presentación del primer caso descrito en Argentina

Variante juvenil de la enfermedad de Sandhoff: presentación del primer caso descrito en Argentina

Incidence and carrier frequency of Sandhoff disease in Saskatchewan determined using a novel substrate with detection by tandem mass spectrometry and molecular genetic analysis

Comprehensive Analysis of HEXB Protein Reveal Forty Two Novel nsSNPs That May Lead to Sandhoff disease (SD) Using Bioinformatics

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