Véronique David | University of Rennes (original) (raw)
Papers by Véronique David
Human Mutation, 2009
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Human Mutation, 2004
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Archives of General Psychiatry, 2009
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Human Molecular Genetics
We report on the prevalence of mutations in the zinc finger transcription factor gene, ZIC2, in a... more We report on the prevalence of mutations in the zinc finger transcription factor gene, ZIC2, in a group of 509 unrelated individuals with isolated holoprosencephaly (HPE) and normal chromosomes. Overall, we encountered 16 HPE patients (from 15 unrelated families) with ZIC2 mutations. Thus, ZIC2 mutation was the apparent cause of HPE in 3-4% of cases. Seven mutations were frameshifts that were predicted to result in loss of function, further supporting the idea that ZIC2 haploinsufficiency can result in HPE. One mutation, an alanine tract expansion which is caused by the expansion of an imperfect trinucleotide repeat, occurred in seven patients from six different families. In three of those families, the father was found to be apparently mosaic for the mutation. We hypothesize that this mutation can arise through errors in somatic recombination, an extremely unusual mutation mechanism. In addition, one mutation resulted in a single amino acid change and one mutation was an in-frame d...
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Nature genetics, 1999
1. Nat Genet. 1999 Nov;23(3):272. Polymorphism in intron 4 of HFE does not compromise haemochroma... more 1. Nat Genet. 1999 Nov;23(3):272. Polymorphism in intron 4 of HFE does not compromise haemochromatosis mutation results. Gomez PS, Parks S, Ries R, Tran TC, Gomez PF, Press RD. Comment on: Nat Genet. 1999 Aug;22(4):325-6. Nat Genet. 1996 Aug;13(4):399-408. ...
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La Presse Médicale, 2007
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PLOS ONE, 2015
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Human genetics, 2003
Holoprosencephaly (HPE) is the most common severe brain anomaly in humans, which results from inc... more Holoprosencephaly (HPE) is the most common severe brain anomaly in humans, which results from incomplete cleavage of the forebrain during early embryogenesis. The aetiology of HPE is very heterogeneous. Among the genetic factors, TGIF ( TG-interacting factor), which codes for a transcription factor modulating the signalling pathway of TGF-beta, was previously implicated. We investigated 127 HPE probands by sequencing their TGIF gene and identified the first nonsense mutation reported so far and also a novel missense mutation, in two families that presented a large range of disease severity. The low number of mutations in TGIF suggests that this gene has no major contribution to the aetiology of HPE and our study confirms the wide clinical heterogeneity of the disease.
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Journal de génétique humaine, 1989
The case of a 4 years old boy, hospitalized for an unexplained coma, is reported. He is the first... more The case of a 4 years old boy, hospitalized for an unexplained coma, is reported. He is the first child of a non-consanguin couple. The psychomotor development of this child was considered as normal up to the age of 18 months; then, a delay in language development, behaviour disorders with an important instability interrupted by episodes of somnolence, were observed. This child was treated for psychotic disorders. At the age of 3 and half, he had two episodes of seizures associated with fever. He was hospitalized for a 24 hours coma (4 years old). An hepatomegaly and a dry, brittle hair were then observed. Hyperammonemia was made obvious by a protein tolerance test. The diagnosis of argininosuccinate lyase (ASAL) deficiency was based on the increased levels of ASA in plasma and urine. The deficiency was proved by a fibroblast culture. With protein restriction, hepatomegaly disappeared, hair became normal, the behaviour disorders and the delay in language development was improved. Ho...
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Orphanet journal of rare diseases, 2007
Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the... more Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like...
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Presse médicale (Paris, France : 1983), 2007
Hereditary type 1 HFE hemochromatosis is associated with homozygosity for the p.Cys282Tyr mutatio... more Hereditary type 1 HFE hemochromatosis is associated with homozygosity for the p.Cys282Tyr mutation of the HFE gene (C282Y mutation). The p.Cys282Tyr mutation of the HFE gene leads to an abnormal reduction in hepatic expression of hepcidin, a protein that appears to control the release of iron from enterocytes and macrophages towards plasma. Abnormally low hepcidin levels promote an increase in the bioavailability of plasma iron, characterized by elevated transferrin saturation and the appearance of non transferrin bound iron. This nontransferrin-bound iron is avidly taken up by the liver, heart, and pancreas, the principal target organs for systemic iron overload. The variable penetrance of this disease is related to environmental and genetic factors. Among the genetic factors, mutations of some newly identified genes may aggravate the phenotype of iron overload associated with homozygosity for the p.Cys282Tyr mutation of the HFE gene; these new genes include those of hemojuvelin (H...
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Pediatric Pulmonology, 2003
Until the year 2000, systematic cystic fibrosis (CF) neonatal screening was only performed in a f... more Until the year 2000, systematic cystic fibrosis (CF) neonatal screening was only performed in a few regions of France. The Brittany region began in 1989, but not the neighboring region of Loire-Atlantique. The present study compares the clinical evolution of both affected populations 10 years after screening was started. Although the 77 screened and 36 nonscreened children were followed in different CF centers, they were included in similar care protocols. The clinical characteristics at diagnosis and their evolution over a 10-year period of all the children affected with CF and born between January 1, 1989 and December 31, 1998, excluding those with meconium ileus, were compared. There were no significant differences in sex ratio, gestational age, anthropometric data at birth, frequency of deltaF508 homozygotes, proportion of pancreatic-insufficient patients, and mean age between the two populations. Age at diagnosis was lower in the screened group (38 days vs. 472 days, P < 10(-7)), as was the delay in supplementation with pancreatic enzymes (1.7 months vs.15.9 months, P < 10(-7)). The proportion of children who were hospitalized at least once was higher among the nonscreened than the screened patients (86% vs. 49%, P < 10(-4)). Z-scores for weight and height were significantly better in the screened population, not only in the first years of life, but also at 5 years old for height and 8 years old for weight. The Shwachman and Brasfield scores were higher among the screened children during the whole period of follow-up. No significant differences in colonization by Pseudomonas aeruginosa nor in lung function were found. Given the homogeneity in the characteristics and the follow-up of both populations, the benefits in terms of nutrition and clinical well-being of neonatal screening appear to be clear, thus confirming the advantages of its general implementation.
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Orphanet Journal of Rare Diseases, 2011
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Nucleic Acids Research, 1990
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Nature Genetics, 1996
1. Nat Genet. 1996 Nov;14(3):251-2. Haemochromatosis and HLA-H. Jouanolle AM, Gandon G, Jézéquel ... more 1. Nat Genet. 1996 Nov;14(3):251-2. Haemochromatosis and HLA-H. Jouanolle AM, Gandon G, Jézéquel P, Blayau M, Campion ML, Yaouanq J, Mosser J, Fergelot P, Chauvel B, Bouric P, Carn G, Andrieux N, Gicquel I, Le Gall JY, David V. Comment on: Nat Genet. ...
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Molecular Human Reproduction, 2000
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Mechanisms of Development, 2009
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The Lancet, 2000
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Journal of Medical Genetics, 2010
Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved ... more Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation. Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH. 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.
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Human Mutation, 2009
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Human Mutation, 2004
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Archives of General Psychiatry, 2009
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Human Molecular Genetics
We report on the prevalence of mutations in the zinc finger transcription factor gene, ZIC2, in a... more We report on the prevalence of mutations in the zinc finger transcription factor gene, ZIC2, in a group of 509 unrelated individuals with isolated holoprosencephaly (HPE) and normal chromosomes. Overall, we encountered 16 HPE patients (from 15 unrelated families) with ZIC2 mutations. Thus, ZIC2 mutation was the apparent cause of HPE in 3-4% of cases. Seven mutations were frameshifts that were predicted to result in loss of function, further supporting the idea that ZIC2 haploinsufficiency can result in HPE. One mutation, an alanine tract expansion which is caused by the expansion of an imperfect trinucleotide repeat, occurred in seven patients from six different families. In three of those families, the father was found to be apparently mosaic for the mutation. We hypothesize that this mutation can arise through errors in somatic recombination, an extremely unusual mutation mechanism. In addition, one mutation resulted in a single amino acid change and one mutation was an in-frame d...
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Bookmarks Related papers MentionsView impact
Nature genetics, 1999
1. Nat Genet. 1999 Nov;23(3):272. Polymorphism in intron 4 of HFE does not compromise haemochroma... more 1. Nat Genet. 1999 Nov;23(3):272. Polymorphism in intron 4 of HFE does not compromise haemochromatosis mutation results. Gomez PS, Parks S, Ries R, Tran TC, Gomez PF, Press RD. Comment on: Nat Genet. 1999 Aug;22(4):325-6. Nat Genet. 1996 Aug;13(4):399-408. ...
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La Presse Médicale, 2007
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PLOS ONE, 2015
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Human genetics, 2003
Holoprosencephaly (HPE) is the most common severe brain anomaly in humans, which results from inc... more Holoprosencephaly (HPE) is the most common severe brain anomaly in humans, which results from incomplete cleavage of the forebrain during early embryogenesis. The aetiology of HPE is very heterogeneous. Among the genetic factors, TGIF ( TG-interacting factor), which codes for a transcription factor modulating the signalling pathway of TGF-beta, was previously implicated. We investigated 127 HPE probands by sequencing their TGIF gene and identified the first nonsense mutation reported so far and also a novel missense mutation, in two families that presented a large range of disease severity. The low number of mutations in TGIF suggests that this gene has no major contribution to the aetiology of HPE and our study confirms the wide clinical heterogeneity of the disease.
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Journal de génétique humaine, 1989
The case of a 4 years old boy, hospitalized for an unexplained coma, is reported. He is the first... more The case of a 4 years old boy, hospitalized for an unexplained coma, is reported. He is the first child of a non-consanguin couple. The psychomotor development of this child was considered as normal up to the age of 18 months; then, a delay in language development, behaviour disorders with an important instability interrupted by episodes of somnolence, were observed. This child was treated for psychotic disorders. At the age of 3 and half, he had two episodes of seizures associated with fever. He was hospitalized for a 24 hours coma (4 years old). An hepatomegaly and a dry, brittle hair were then observed. Hyperammonemia was made obvious by a protein tolerance test. The diagnosis of argininosuccinate lyase (ASAL) deficiency was based on the increased levels of ASA in plasma and urine. The deficiency was proved by a fibroblast culture. With protein restriction, hepatomegaly disappeared, hair became normal, the behaviour disorders and the delay in language development was improved. Ho...
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Orphanet journal of rare diseases, 2007
Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the... more Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like...
Bookmarks Related papers MentionsView impact
Presse médicale (Paris, France : 1983), 2007
Hereditary type 1 HFE hemochromatosis is associated with homozygosity for the p.Cys282Tyr mutatio... more Hereditary type 1 HFE hemochromatosis is associated with homozygosity for the p.Cys282Tyr mutation of the HFE gene (C282Y mutation). The p.Cys282Tyr mutation of the HFE gene leads to an abnormal reduction in hepatic expression of hepcidin, a protein that appears to control the release of iron from enterocytes and macrophages towards plasma. Abnormally low hepcidin levels promote an increase in the bioavailability of plasma iron, characterized by elevated transferrin saturation and the appearance of non transferrin bound iron. This nontransferrin-bound iron is avidly taken up by the liver, heart, and pancreas, the principal target organs for systemic iron overload. The variable penetrance of this disease is related to environmental and genetic factors. Among the genetic factors, mutations of some newly identified genes may aggravate the phenotype of iron overload associated with homozygosity for the p.Cys282Tyr mutation of the HFE gene; these new genes include those of hemojuvelin (H...
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Pediatric Pulmonology, 2003
Until the year 2000, systematic cystic fibrosis (CF) neonatal screening was only performed in a f... more Until the year 2000, systematic cystic fibrosis (CF) neonatal screening was only performed in a few regions of France. The Brittany region began in 1989, but not the neighboring region of Loire-Atlantique. The present study compares the clinical evolution of both affected populations 10 years after screening was started. Although the 77 screened and 36 nonscreened children were followed in different CF centers, they were included in similar care protocols. The clinical characteristics at diagnosis and their evolution over a 10-year period of all the children affected with CF and born between January 1, 1989 and December 31, 1998, excluding those with meconium ileus, were compared. There were no significant differences in sex ratio, gestational age, anthropometric data at birth, frequency of deltaF508 homozygotes, proportion of pancreatic-insufficient patients, and mean age between the two populations. Age at diagnosis was lower in the screened group (38 days vs. 472 days, P < 10(-7)), as was the delay in supplementation with pancreatic enzymes (1.7 months vs.15.9 months, P < 10(-7)). The proportion of children who were hospitalized at least once was higher among the nonscreened than the screened patients (86% vs. 49%, P < 10(-4)). Z-scores for weight and height were significantly better in the screened population, not only in the first years of life, but also at 5 years old for height and 8 years old for weight. The Shwachman and Brasfield scores were higher among the screened children during the whole period of follow-up. No significant differences in colonization by Pseudomonas aeruginosa nor in lung function were found. Given the homogeneity in the characteristics and the follow-up of both populations, the benefits in terms of nutrition and clinical well-being of neonatal screening appear to be clear, thus confirming the advantages of its general implementation.
Bookmarks Related papers MentionsView impact
Orphanet Journal of Rare Diseases, 2011
Bookmarks Related papers MentionsView impact
Nucleic Acids Research, 1990
Bookmarks Related papers MentionsView impact
Nature Genetics, 1996
1. Nat Genet. 1996 Nov;14(3):251-2. Haemochromatosis and HLA-H. Jouanolle AM, Gandon G, Jézéquel ... more 1. Nat Genet. 1996 Nov;14(3):251-2. Haemochromatosis and HLA-H. Jouanolle AM, Gandon G, Jézéquel P, Blayau M, Campion ML, Yaouanq J, Mosser J, Fergelot P, Chauvel B, Bouric P, Carn G, Andrieux N, Gicquel I, Le Gall JY, David V. Comment on: Nat Genet. ...
Bookmarks Related papers MentionsView impact
Molecular Human Reproduction, 2000
Bookmarks Related papers MentionsView impact
Mechanisms of Development, 2009
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The Lancet, 2000
Bookmarks Related papers MentionsView impact
Journal of Medical Genetics, 2010
Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved ... more Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation. Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH. 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.
Bookmarks Related papers MentionsView impact