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

Background Zellweger 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. Methods We identified 5 ZS patients fro...
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Autor*in:	Levesque, Sebastien [verfasserIn] Morin, Charles Guay, Simon-Pierre Villeneuve, Josee Marquis, Pascale Yik, Wing Yan Jiralerspong, Sarn Bouchard, Luigi Steinberg, Steven Hacia, Joseph G Dewar, Ken Braverman, Nancy E

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2012

Schlagwörter:	Zellweger syndrome Founder effect Peroxisome biogenesis disorders Next generation sequencing

Anmerkung:	© Levesque et al.; licensee BioMed Central Ltd. 2012

Übergeordnetes Werk:	Enthalten in: BMC medical genetics - London : BioMed Central, 2000, 13(2012), 1 vom: 15. Aug.
Übergeordnetes Werk:	volume:13 ; year:2012 ; number:1 ; day:15 ; month:08

Links:	Volltext

DOI / URN:	10.1186/1471-2350-13-72

Katalog-ID:	SPR027490734

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245	1	2	\|a A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population
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520			\|a Background Zellweger 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. Methods We 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. Results A 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. Conclusion We 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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allfields	10.1186/1471-2350-13-72 doi (DE-627)SPR027490734 (SPR)1471-2350-13-72-e DE-627 ger DE-627 rakwb eng Levesque, Sebastien verfasserin aut A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Levesque et al.; licensee BioMed Central Ltd. 2012 Background Zellweger 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. Methods We 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. Results A 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. Conclusion We 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. Zellweger syndrome (dpeaa)DE-He213 Founder effect (dpeaa)DE-He213 Peroxisome biogenesis disorders (dpeaa)DE-He213 Next generation sequencing (dpeaa)DE-He213 Morin, Charles aut Guay, Simon-Pierre aut Villeneuve, Josee aut Marquis, Pascale aut Yik, Wing Yan aut Jiralerspong, Sarn aut Bouchard, Luigi aut Steinberg, Steven aut Hacia, Joseph G aut Dewar, Ken aut Braverman, Nancy E aut Enthalten in BMC medical genetics London : BioMed Central, 2000 13(2012), 1 vom: 15. Aug. (DE-627)326643788 (DE-600)2041359-2 1471-2350 nnns volume:13 year:2012 number:1 day:15 month:08 https://dx.doi.org/10.1186/1471-2350-13-72 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2012 1 15 08
spelling	10.1186/1471-2350-13-72 doi (DE-627)SPR027490734 (SPR)1471-2350-13-72-e DE-627 ger DE-627 rakwb eng Levesque, Sebastien verfasserin aut A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Levesque et al.; licensee BioMed Central Ltd. 2012 Background Zellweger 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. Methods We 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. Results A 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. Conclusion We 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. Zellweger syndrome (dpeaa)DE-He213 Founder effect (dpeaa)DE-He213 Peroxisome biogenesis disorders (dpeaa)DE-He213 Next generation sequencing (dpeaa)DE-He213 Morin, Charles aut Guay, Simon-Pierre aut Villeneuve, Josee aut Marquis, Pascale aut Yik, Wing Yan aut Jiralerspong, Sarn aut Bouchard, Luigi aut Steinberg, Steven aut Hacia, Joseph G aut Dewar, Ken aut Braverman, Nancy E aut Enthalten in BMC medical genetics London : BioMed Central, 2000 13(2012), 1 vom: 15. Aug. (DE-627)326643788 (DE-600)2041359-2 1471-2350 nnns volume:13 year:2012 number:1 day:15 month:08 https://dx.doi.org/10.1186/1471-2350-13-72 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2012 1 15 08
allfields_unstemmed	10.1186/1471-2350-13-72 doi (DE-627)SPR027490734 (SPR)1471-2350-13-72-e DE-627 ger DE-627 rakwb eng Levesque, Sebastien verfasserin aut A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Levesque et al.; licensee BioMed Central Ltd. 2012 Background Zellweger 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. Methods We 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. Results A 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. Conclusion We 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. Zellweger syndrome (dpeaa)DE-He213 Founder effect (dpeaa)DE-He213 Peroxisome biogenesis disorders (dpeaa)DE-He213 Next generation sequencing (dpeaa)DE-He213 Morin, Charles aut Guay, Simon-Pierre aut Villeneuve, Josee aut Marquis, Pascale aut Yik, Wing Yan aut Jiralerspong, Sarn aut Bouchard, Luigi aut Steinberg, Steven aut Hacia, Joseph G aut Dewar, Ken aut Braverman, Nancy E aut Enthalten in BMC medical genetics London : BioMed Central, 2000 13(2012), 1 vom: 15. Aug. (DE-627)326643788 (DE-600)2041359-2 1471-2350 nnns volume:13 year:2012 number:1 day:15 month:08 https://dx.doi.org/10.1186/1471-2350-13-72 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2012 1 15 08
allfieldsGer	10.1186/1471-2350-13-72 doi (DE-627)SPR027490734 (SPR)1471-2350-13-72-e DE-627 ger DE-627 rakwb eng Levesque, Sebastien verfasserin aut A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Levesque et al.; licensee BioMed Central Ltd. 2012 Background Zellweger 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. Methods We 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. Results A 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. Conclusion We 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. Zellweger syndrome (dpeaa)DE-He213 Founder effect (dpeaa)DE-He213 Peroxisome biogenesis disorders (dpeaa)DE-He213 Next generation sequencing (dpeaa)DE-He213 Morin, Charles aut Guay, Simon-Pierre aut Villeneuve, Josee aut Marquis, Pascale aut Yik, Wing Yan aut Jiralerspong, Sarn aut Bouchard, Luigi aut Steinberg, Steven aut Hacia, Joseph G aut Dewar, Ken aut Braverman, Nancy E aut Enthalten in BMC medical genetics London : BioMed Central, 2000 13(2012), 1 vom: 15. Aug. (DE-627)326643788 (DE-600)2041359-2 1471-2350 nnns volume:13 year:2012 number:1 day:15 month:08 https://dx.doi.org/10.1186/1471-2350-13-72 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2012 1 15 08
allfieldsSound	10.1186/1471-2350-13-72 doi (DE-627)SPR027490734 (SPR)1471-2350-13-72-e DE-627 ger DE-627 rakwb eng Levesque, Sebastien verfasserin aut A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Levesque et al.; licensee BioMed Central Ltd. 2012 Background Zellweger 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. Methods We 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. Results A 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. Conclusion We 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. Zellweger syndrome (dpeaa)DE-He213 Founder effect (dpeaa)DE-He213 Peroxisome biogenesis disorders (dpeaa)DE-He213 Next generation sequencing (dpeaa)DE-He213 Morin, Charles aut Guay, Simon-Pierre aut Villeneuve, Josee aut Marquis, Pascale aut Yik, Wing Yan aut Jiralerspong, Sarn aut Bouchard, Luigi aut Steinberg, Steven aut Hacia, Joseph G aut Dewar, Ken aut Braverman, Nancy E aut Enthalten in BMC medical genetics London : BioMed Central, 2000 13(2012), 1 vom: 15. Aug. (DE-627)326643788 (DE-600)2041359-2 1471-2350 nnns volume:13 year:2012 number:1 day:15 month:08 https://dx.doi.org/10.1186/1471-2350-13-72 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2012 1 15 08
language	English
source	Enthalten in BMC medical genetics 13(2012), 1 vom: 15. Aug. volume:13 year:2012 number:1 day:15 month:08
sourceStr	Enthalten in BMC medical genetics 13(2012), 1 vom: 15. Aug. volume:13 year:2012 number:1 day:15 month:08
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Zellweger syndrome Founder effect Peroxisome biogenesis disorders Next generation sequencing
isfreeaccess_bool	true
container_title	BMC medical genetics
authorswithroles_txt_mv	Levesque, Sebastien @@aut@@ Morin, Charles @@aut@@ Guay, Simon-Pierre @@aut@@ Villeneuve, Josee @@aut@@ Marquis, Pascale @@aut@@ Yik, Wing Yan @@aut@@ Jiralerspong, Sarn @@aut@@ Bouchard, Luigi @@aut@@ Steinberg, Steven @@aut@@ Hacia, Joseph G @@aut@@ Dewar, Ken @@aut@@ Braverman, Nancy E @@aut@@
publishDateDaySort_date	2012-08-15T00:00:00Z
hierarchy_top_id	326643788
id	SPR027490734
language_de	englisch
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Increased incidence of ZS has been suspected in French-Canadians of the Saguenay-Lac-St-Jean region (SLSJ) of Quebec, but this remains unsolved. Methods We 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. Results A 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. Conclusion We 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. 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author	Levesque, Sebastien
spellingShingle	Levesque, Sebastien misc Zellweger syndrome misc Founder effect misc Peroxisome biogenesis disorders misc Next generation sequencing A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population
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topic_title	A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population Zellweger syndrome (dpeaa)DE-He213 Founder effect (dpeaa)DE-He213 Peroxisome biogenesis disorders (dpeaa)DE-He213 Next generation sequencing (dpeaa)DE-He213
topic	misc Zellweger syndrome misc Founder effect misc Peroxisome biogenesis disorders misc Next generation sequencing
topic_unstemmed	misc Zellweger syndrome misc Founder effect misc Peroxisome biogenesis disorders misc Next generation sequencing
topic_browse	misc Zellweger syndrome misc Founder effect misc Peroxisome biogenesis disorders misc Next generation sequencing
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title	A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population
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title_full	A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population
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author_browse	Levesque, Sebastien Morin, Charles Guay, Simon-Pierre Villeneuve, Josee Marquis, Pascale Yik, Wing Yan Jiralerspong, Sarn Bouchard, Luigi Steinberg, Steven Hacia, Joseph G Dewar, Ken Braverman, Nancy E
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doi_str_mv	10.1186/1471-2350-13-72
title_sort	founder mutation in the pex6 gene is responsible for increased incidence of zellweger syndrome in a french canadian population
title_auth	A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population
abstract	Background Zellweger 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. Methods We 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. Results A 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. Conclusion We 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. © Levesque et al.; licensee BioMed Central Ltd. 2012
abstractGer	Background Zellweger 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. Methods We 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. Results A 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. Conclusion We 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. © Levesque et al.; licensee BioMed Central Ltd. 2012
abstract_unstemmed	Background Zellweger 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. Methods We 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. Results A 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. Conclusion We 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. © Levesque et al.; licensee BioMed Central Ltd. 2012
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title_short	A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population
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A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population

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