Spectrum of<i>PEX6</i>mutations in Zellweger syndrome spectrum patients

Ebberink, Merel S.; Kofster, Janet; Wanders, Ronald J. A.; Waterham, Hans R.

doi:10.1002/humu.21153

Cited by 28 publications

(25 citation statements)

References 8 publications

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“…Among the result, one patient (case 19) was diagnosed with Zellweger syndrome with PEX6 gene compound heterozygous mutations, PEX6 gene mutation is reported to be associated with Peroxisome biogenesis disorder 4A/B2930. The patient in our study was a 5.9-year-old girl exhibiting mental and motor retardation for 5 years, and with deterioration for 3 months (Clinical features and auxiliary examinations are included in Table 2).…”

Section: Discussionmentioning

confidence: 79%

The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies

Wang

Yin

et al. 2016

Sci Rep

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Leukoencephalopathies are diseases with high clinical heterogeneity. In clinical work, it’s difficult for doctors to make a definite etiological diagnosis. Here, we designed a custom probe library which contains the known pathogenic genes reported to be associated with Leukoencephalopathies, and performed targeted gene capture and massively parallel sequencing (MPS) among 49 Chinese patients who has white matter damage as the main imaging changes, and made the validation by Sanger sequencing for the probands’ parents. As result, a total of 40.8% (20/49) of the patients identified pathogenic mutations, including four associated with metachromatic leukodystrophy, three associated with vanishing white matter leukoencephalopathy, three associated with mitochondrial complex I deficiency, one associated with Globoid cell leukodystrophy (or Krabbe diseases), three associated with megalencephalic leukoencephalopathy with subcortical cysts, two associated with Pelizaeus-Merzbacher disease, two associated with X-linked adrenoleukodystrophy, one associated with Zellweger syndrome and one associated with Alexander disease. Targeted capture and MPS enables to identify mutations of all classes causing leukoencephalopathy. Our study combines targeted capture and MPS technology with clinical and genetic diagnosis and highlights its usefulness for rapid and comprehensive genetic testing in the clinical setting. This method will also expand our knowledge of the genetic and clinical spectra of leukoencephalopathy.

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Section: Discussionmentioning

confidence: 79%

The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies

Wang

Yin

et al. 2016

Sci Rep

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“…Here, we report a single PEX6 mutation in all ZS cases in French-Canadians from the SLSJ region. There is strong evidence that this is a founder mutation given the elevated incidence of ZS in the population and no PEX6 mutation hotspots have been identified large patient cohorts [25]. In addition, three-generation pedigrees of the four affected families from SLSJ did not reveal any close relationship that could otherwise explain the observed homozygosity for this mutation.…”

Section: Discussionmentioning

confidence: 99%

“…In more than 100 ZS patients with PEX6 mutations, c.802_815del was observed only 3 times in other populations, in patients with compound heterozygosity for this allele and a second, different PEX6 allele. One was a US patient with unknown ethnicity [26] (also listed as http://www.dbpex.org, PEX6_30001), the second was of French-Canadian descent but not clearly from the SLSJ region ( http://www.dbpex.org, PEX6_00039), and the third was from a European population [25]. In cells from the US patient, Matsumoto and colleagues showed the presence of a shorter PEX6 transcript due to the loss of 264 nucleotides at the end of exon 1 by RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population

et al. 2012

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BackgroundZellweger syndrome (ZS) is a peroxisome biogenesis disorder due to mutations in any one of 13 PEX genes. Increased incidence of ZS has been suspected in French-Canadians of the Saguenay-Lac-St-Jean region (SLSJ) of Quebec, but this remains unsolved.MethodsWe identified 5 ZS patients from SLSJ diagnosed by peroxisome dysfunction between 1990–2010 and sequenced all coding exons of known PEX genes in one patient using Next Generation Sequencing (NGS) for diagnostic confirmation.ResultsA homozygous mutation (c.802_815del, p.[Val207_Gln294del, Val76_Gln294del]) in PEX6 was identified and then shown in 4 other patients. Parental heterozygosity was confirmed in all. Incidence of ZS was estimated to 1 in 12,191 live births, with a carrier frequency of 1 in 55. In addition, we present data suggesting that this mutation abolishes a SF2/ASF splice enhancer binding site, resulting in the use of two alternative cryptic donor splice sites and predicted to encode an internally deleted in-frame protein.ConclusionWe report increased incidence of ZS in French-Canadians of SLSJ caused by a PEX6 founder mutation. To our knowledge, this is the highest reported incidence of ZS worldwide. These findings have implications for carrier screening and support the utility of NGS for molecular confirmation of peroxisomal disorders.

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“…HRM analysis has been used to detect genetic mutations that cause human diseases in genes such as RET, CFTR, and PEX6 (Margraf et al, 2007;Audrezet et al, 2008;Ebberink et al, 2010). Poultry infectious bronchitis and infectious bursal disease virus mutations have been detected and reported previously (Hewson et al, 2010;Ghorashi et al, 2011).…”

Section: Hrm Technique and Its Application For Detecting Genotypes Afmentioning

confidence: 99%

High-resolution melting curve analysis of the ADSL and LPL genes and their correlation with meat quality and blood parameters in chickens

Zhang¹,

Li²,

Lou³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Adenylosuccinate lyase (ADSL) and lipoprotein lipase (LPL) are key enzymes in the metabolism of inosine monophosphate (IMP) and fat mass, which are important factors in meat quality evaluation. In this study, we selected 50 hens from the ISA B-line layers and Guangxi Yellow chickens, slaughtered the chickens at 120 days old, and analyzed polymorphisms in the ADSL and LPL genes using the highresolution melting curve method. Blood lipid parameters, intramuscular fat (IMF), and IMP content were higher (P < 0.05) in Guangxi Yellow chickens than in ISA B-line layers, while LPL activity was lower (P < 0.05). In exon 2 of the ADSL gene, a C3484T mutation was identified. In both breeds, the CC genotype showed the highest IMP, and IMP was the lowest in the TT genotype. In the 5ꞌ regulatory region of the LPL gene, a C293T mutation was identified. In both breeds, the CC genotype showed the lowest LPL and IMF, while IMF was the highest in the TT genotype. The percentages of individuals with the TT type in the ADSL (2015) gene, which was associated with the lowest IMP, were 16.0 and 52.0% in Guangxi chickens and ISA layers, respectively. The percentages of individuals with the CC type of the LPL gene, which was associated with the lowest LPL and IMF, were 28.0 and 44.0%, respectively. The ADSL and LPL gene mutations are correlated with differences in meat quality in different chicken breeds, and high-resolution melting curve is an effective prediction technology for these mutations.

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Spectrum ofPEX6mutations in Zellweger syndrome spectrum patients

Cited by 28 publications

References 8 publications

The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies

The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies

A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population

High-resolution melting curve analysis of the ADSL and LPL genes and their correlation with meat quality and blood parameters in chickens

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