Characterisation of a 5-bp deletion in exon 4 of the factor VIII gene: concordance with slipped-mispairing at DNA replication

Si, Bidichandani; Wg, Lanyon; Jm, Connor

doi:10.1007/bf00201612

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…3 Single-strand conformational polymorphism analysis was performed using a previously described protocol. 28 analysis for the CAG triplet repeat expansions seen in spinocerebellar ataxia types 1 and 3 showed normal results.…”

Section: Methodsmentioning

confidence: 94%

Very Late-Onset Friedreich Ataxia Despite Large GAA Triplet Repeat Expansions

Bidichandani¹,

García²,

Patel³

et al. 2000

Arch Neurol

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Section: Methodsmentioning

confidence: 94%

Very Late-Onset Friedreich Ataxia Despite Large GAA Triplet Repeat Expansions

Bidichandani¹,

García²,

Patel³

et al. 2000

Arch Neurol

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“…Forty protein-truncating variants, including 22 indels and 18 nonsense variants, were identified in 49 patients ( Table 1 ). Long poly-A and poly-T runs (at least 6 consecutive adenines or thymine) are hotspots for indels due to slipped mispairing or intragenic recombination, which are mechanisms responsible for indel formation ( Krawczak and Cooper, 1991 ; Bidichandani et al, 1994 ; Nakaya et al, 2001 ; Bogdanova et al, 2002 ). In this study, four indels recurred at positions c.3637, c.4379, and c.4825 in three, three, and two patients, respectively, all the indels are within the poly-A runs.…”

Section: Resultsmentioning

confidence: 99%

Variant spectrum of F8 and F9 in hemophilia patients from southern China and 26 novel variants

Li,

He,

Chen

et al. 2023

Front. Genet.

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Hemophilia, an X-linked recessive disorder, is characterized by spontaneous or trauma-induced prolonged bleeding. It is classified as hemophilia A when caused by variants in the F8 gene, and hemophilia B when caused by F9 variants. Few studies have described hemophilia variants in the Chinese population. This study aimed to investigate the clinical and genetic profiles of 193 hemophilia patients from southern China. Utilizing Sanger sequencing, multiplex ligation-dependent probe amplification, gap detection, long-range PCR, and multiplex PCR, we identified both F8 and F9 gene variants. Pregnant women with a history of hemophilia A offspring underwent amniocentesis or villus sampling for the variant detection. Variants in F8 and F9 were pinpointed in 183 patients, with 26 being novel discoveries. Notably, genetic testing was absent in the initial evaluation of 133 out of 161 patients, leading to a protracted average definitive diagnosis timeline of 2 years. Remarkably, two hemophilia A cases with anticipated severe phenotypes due to protein-truncating variants presented with only moderate or mild clinical manifestations. Among the 40 fetuses tested, 34 were males, with 17 exhibiting hemizygous variants in the F8 gene. Our results contribute to the broader understanding of F8 and F9 variant spectrum and highlight the underuse of genetic analyses in southern China.

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“…It is generally accepted that intragenic recombination could be generated by errors of nucleotide pairing during DNA replication [22]. A modified ‘slipped‐mispairing’ model proposed by Krawczak and Cooper [23] has been advocated to explain small deletions found in human genome as well as within the F8 gene [24]. This model calls for the existence of homology between the sequence flanking the deletion and the adjacent DNA sequence.…”

Section: Resultsmentioning

confidence: 99%

The spectrum of the factor 8 (F8) defects in Taiwanese patients with haemophilia A

Chang

Chen

et al. 2008

Haemophilia

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Summary. Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by various types of pathological defects in the factor VIII gene (F8), which encodes coagulation factor VIII (FVIII). To date, several studies on the spectra of F8 defects have been performed in Western populations, but similar studies in Asian races are scarce. Here, we report the distribution of the mutations within the F8 gene in 31 Taiwanese unrelated HA patients (19 severe and 10 moderate/mild males and two severe females). Of these, 12 (38.7%) and one (3.2%) severe males were genotyped with the recurrent IVS22 and IVS1 inversion, respectively, similar to that in general populations (IVS22: 40-50%; IVS1: 2-5%). The F8 defects in the remaining 18 inversion-negative patients cover a wide spectrum, in which 17 different mutations were identified (10 missense and three nonsense mutations, and two small and two large deletions).Eleven of these mutations are novel: seven caused missense substitutions and four resulted in truncated proteins. To assess the putative pathogenetic impacts of the newly amino acid substitutions, computer analyses were performed based on molecular 3D modelling. The degree of conservation in crossspecies FVIIIs and the position in known functional FVIII regions were studied. The novel missense mutations found in our series all occurred at evolutionary conserved residues that may carry a functional importance in our analyses. The results of this study add the short list of Taiwanese/Chinese F8 mutations, and will enhance our understanding of the molecular basis of FVIII function and the mechanism underlying HA.

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Characterisation of a 5-bp deletion in exon 4 of the factor VIII gene: concordance with slipped-mispairing at DNA replication

Cited by 5 publications

References 19 publications

Very Late-Onset Friedreich Ataxia Despite Large GAA Triplet Repeat Expansions

Very Late-Onset Friedreich Ataxia Despite Large GAA Triplet Repeat Expansions

Variant spectrum of F8 and F9 in hemophilia patients from southern China and 26 novel variants

The spectrum of the factor 8 (F8) defects in Taiwanese patients with haemophilia A

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