Christine Francannet

University Hospital Estaing of Clermont-Ferrand, Clermont, Auvergne, France

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Publications (78)214.2 Total impact

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    ABSTRACT: The prognosis and early neonatal management of the VACTERL association depend mainly on the severity of malformations ascertained prenatally. Here we reviewed the spectrum of clinical features observed in cases of VACTERL association ascertained prenatally through ultrasound examination but examined at birth and compared them with cases ascertained postnatally. From 1995 to 2011, a total of 19 cases of VACTERL association were observed in our center; 10 were ascertained prenatally and confirmed after birth whereas 9 were ascertained only after birth. The types and frequencies of malformations observed prenatally were as follows: renal malformations (45%), tracheoesophageal fistula (44%), cardiac malformations (20%), vertebral (13%), and limb (11%) defects. Anal atresia was never detected using routine prenatal ultrasound examination. Further studies of fetuses with the VACTERL association are necessary to better delineate the malformations spectrum observed prenatally to improve the early recognition of the VACTERL association. Birth Defects Research (Part A), 2014. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 06/2015; DOI:10.1002/bdra.23346 · 2.21 Impact Factor
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    ABSTRACT: The dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene, located on chromosome 21q22.13 within the Down syndrome critical region, has been implicated in syndromic intellectual disability associated with Down syndrome and autism. DYRK1A has a critical role in brain growth and development primarily by regulating cell proliferation, neurogenesis, neuronal plasticity and survival. Several patients have been reported with chromosome 21 aberrations such as partial monosomy, involving multiple genes including DYRK1A. In addition, seven other individuals have been described with chromosomal rearrangements, intragenic deletions or truncating mutations that disrupt specifically DYRK1A. Most of these patients have microcephaly and all have significant intellectual disability. In the present study, we report 10 unrelated individuals with DYRK1A-associated intellectual disability (ID) who display a recurrent pattern of clinical manifestations including primary or acquired microcephaly, ID ranging from mild to severe, speech delay or absence, seizures, autism, motor delay, deep-set eyes, poor feeding and poor weight gain. We identified unique truncating and non-synonymous mutations (three nonsense, four frameshift and two missense) in DYRK1A in nine patients and a large chromosomal deletion that encompassed DYRK1A in one patient. On the basis of increasing identification of mutations in DYRK1A, we suggest that this gene be considered potentially causative in patients presenting with ID, primary or acquired microcephaly, feeding problems and absent or delayed speech with or without seizures.European Journal of Human Genetics advance online publication, 29 April 2015; doi:10.1038/ejhg.2015.29.
    European journal of human genetics: EJHG 04/2015; DOI:10.1038/ejhg.2015.29 · 4.23 Impact Factor
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    ABSTRACT: Microdeletions of 17q12 encompassing TCF2 are associated with maturity-onset of diabetes of the young type 5, cystic renal disease, pancreatic atrophy, Mullerian aplasia in females and variable cognitive impairment. We report on a patient with a de novo 17q12 microdeletion, 1.8 Mb in size, associated with congenital diaphragmatic hernia (CDH). The 5-year-old male patient presented multicystic renal dysplasia kidneys, minor facial dysmorphic features and skeletal anomalies, but neither developmental delay nor behavioral abnormalities. CDH has been previously associated with the 17q12 microdeletion syndrome only in one prenatal case. The present study reinforces the hypothesis that CDH is part of the phenotype for 17q12 microdeletion and that 17q12 encompasses candidate(s) gene(s) involved in diaphragm development. We suggest that PIGW, a gene involved in an early step of GPI biosynthesis, could be a strong candidate gene for CDH. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 01/2015; 167(1). DOI:10.1002/ajmg.a.36840 · 2.05 Impact Factor
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    ABSTRACT: High proportion of disease-associated copy number variant maps to chromosome 17. Genomic studies have provided an insight into its complex genomic structure such as relative abundance of segmental duplication and intercepted repetitive elements. 17q21.31, 17q11.2 and 17q12 loci are well known on this chromosome and are associated with microdeletion and microduplication syndrome. No syndrome associated with 17q21.33 locus have been described. We report clinical, cytogenetic and molecular investigations of a 13 years-old girl admitted for evaluation of microcephaly, scoliosis, skeletal defects and learning difficulties. We carried out detailed analysis of the clinical phenotype of this patient and investigated the genetic basis using Agilent 180K Array Comparative Genomic Hybridization. We identified a ∼ 0.9 Mb de novo microduplication on chromosome 17q21.33. Four genes, COL1A1, SGCA, PPP1R9B and CHAD located within the duplicated region are possible candidates for clinical features present in our patients. Gene expression studies by real-time RT-PCR assay only showed an overexpression of SGCA (P<0.01), a component of the dystrophin glycoprotein complex. Defect of SGCA was previously shown to lead to severe childhood autosomal recessive muscular dystrophy (LGMD2D) which result in progressive muscle weakness and can also be associated with hyperlordosis or scoliosis. Further cases with similar duplications are expected to be diagnosed. This will contribute to the delineation of this potential new microduplication syndrome and to improve genetic counseling.
    European Journal of Medical Genetics 10/2014; 57(10). DOI:10.1016/j.ejmg.2014.07.003 · 1.49 Impact Factor
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    ABSTRACT: BACKGROUND: Intellectual disability (ID) is characterised by an extreme genetic heterogeneity. Several hundred genes have been associated to monogenic forms of ID, considerably complicating molecular diagnostics. Trio-exome sequencing was recently proposed as a diagnostic approach, yet remains costly for a general implementation. METHODS: We report the alternative strategy of targeted high-throughput sequencing of 217 genes in which mutations had been reported in patients with ID or autism as the major clinical concern. We analysed 106 patients with ID of unknown aetiology following array-CGH analysis and other genetic investigations. Ninety per cent of these patients were males, and 75% sporadic cases. RESULTS: We identified 26 causative mutations: 16 in X-linked genes (ATRX, CUL4B, DMD, FMR1, HCFC1, IL1RAPL1, IQSEC2, KDM5C, MAOA, MECP2, SLC9A6, SLC16A2, PHF8) and 10 de novo in autosomal-dominant genes (DYRK1A, GRIN1, MED13L, TCF4, RAI1, SHANK3, SLC2A1, SYNGAP1). We also detected four possibly causative mutations (eg, in NLGN3) requiring further investigations. We present detailed reasoning for assigning causality for each mutation, and associated patients' clinical information. Some genes were hit more than once in our cohort, suggesting they correspond to more frequent ID-associated conditions (KDM5C, MECP2, DYRK1A, TCF4). We highlight some unexpected genotype to phenotype correlations, with causative mutations being identified in genes associated to defined syndromes in patients deviating from the classic phenotype (DMD, TCF4, MECP2). We also bring additional supportive (HCFC1, MED13L) or unsupportive (SHROOM4, SRPX2) evidences for the implication of previous candidate genes or mutations in cognitive disorders. CONCLUSIONS: With a diagnostic yield of 25% targeted sequencing appears relevant as a first intention test for the diagnosis of ID, but importantly will also contribute to a better understanding regarding the specific contribution of the many genes implicated in ID and autism.
    Journal of Medical Genetics 08/2014; DOI:10.1136/jmedgenet-2014-102554 · 5.64 Impact Factor
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    ABSTRACT: Overgrowth conditions are a heterogeneous group of disorders characterised by increased growth and variable features, including macrocephaly, distinctive facial appearance and various degrees of learning difficulties and intellectual disability. Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively. NSD1 and EZH2 are both histone-modifying enzymes. These two epigenetic writers catalyse two specific post-translational modifications of histones: methylation of histone 3 lysine 36 (H3K36) and lysine 27 (H3K27). We postulated that mutations in writers of these two chromatin marks could cause overgrowth conditions, resembling Sotos or Weaver syndromes, in patients with no NSD1 or EZH2 abnormalities.
    Journal of Medical Genetics 05/2014; 51(8). DOI:10.1136/jmedgenet-2014-102402 · 5.64 Impact Factor
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    ABSTRACT: Congenital malformations occur in 3-4% of live births. Their prenatal detection is performed by ultrasound screening. Any announcement about a suspected malformation is a source of stress for the parents, and misdiagnosis during ultrasound screening can lead to expensive and sometimes iatrogenic medical interventions. In this study, we aim to determine the false-positive rate, first overall and then by anatomical system, of ultrasound screening for congenital malformations in the second and third trimesters of pregnancy. Our sample includes all children born between 1 January, 2006, and 31 December, 2009, in the French region of Auvergne, whose mother had a prenatal ultrasound diagnosis of a congenital malformation during the second or third trimester of pregnancy confirmed by a follow-up ultrasound examination by an expert consultant ultrasonographer. The study included 526 fetuses, divided in 3 groups: false positives, diagnostic misclassifications, and true positives. The rates of false positives and diagnostic misclassifications were calculated for the sample as a whole and then by anatomical system. Overall, the false-positive rate was 8.8% and the rate of diagnostic misclassification 9.2%. The highest false-positive rates were found for renal and gastrointestinal tract malformations, and the highest diagnostic misclassification rates for cerebral and cardiac malformations. The diagnostic misclassification rate was significantly higher than the false-positive rate for cardiac malformations. The false-positive rate during prenatal ultrasound is not insignificant; these misdiagnoses cause psychological stress for the parents and overmedicalisation of the pregnancy and the child.
    BMC Pregnancy and Childbirth 03/2014; 14(1):112. DOI:10.1186/1471-2393-14-112 · 2.15 Impact Factor
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    ABSTRACT: Three overlapping conditions, namely Rothmund-Thomson (RTS), Baller-Gerold (BGS) and RAPADILINO syndromes, have been attributed to RECQL4 mutations. Differential diagnoses depend on the clinical presentation, but the number of known genes remains low, leading to the widespread prescription of RECQL4 sequencing. The aim of our study was therefore to determine the best clinical indicators for the presence of RECQL4 mutations in a series of 39 patients referred for RECQL4 molecular analysis and belonging to the RTS (27 cases) and BGS (12 cases) spectrum. One or two deleterious RECQL4 mutations were found in 10/27 patients referred for RTS diagnosis. Clinical and molecular reevaluation led to a different diagnosis in 7/17 negative cases, including Clericuzio-type Poikiloderma with Neutropenia, hereditary sclerosing poikiloderma, and Craniosynostosis/anal anomalies/porokeratosis. No RECQL4 mutations were found in the BGS group without poikiloderma, confirming that RECQL4 sequencing was not indicated in this phenotype. One chromosomal abnormality and one TWIST mutation was found in this cohort. This study highlights the search for differential diagnoses before the prescription of RECQL4 sequencing in this clinically heterogeneous group. The combination of clinically-defined subgroups and next-generation sequencing will hopefully bring to light new molecular bases of syndromes with poikiloderma, as well as BGS without poikiloderma.
    Clinical Genetics 02/2014; DOI:10.1111/cge.12361 · 3.65 Impact Factor
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    ABSTRACT: Interstitial duplication within the long arm of chromosome 20 is an uncommon chromosome structural abnormality. We report here the clinical and molecular characterization associated with pure 20q13.2 duplication in three unrelated patients. The most frequent clinical features were developmental delay, facial dysmorphism, cardiac malformation and skeletal anomalies. All DNA gains occurred de novo, ranging from 1.1 Mb to 11.5 Mb. Compared with previously reported conventional cytogenetic analyses, oligonucleotides array CGH allowed us to refine breakpoints and determine the genes of interest in the region. Involvement of SALL4 in cardiac malformations and NFATC2 gene disruption in both cardiac and skeletal anomalies are discussed.
    European journal of medical genetics 01/2014; 57(4). DOI:10.1016/j.ejmg.2013.12.013 · 1.49 Impact Factor
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    ABSTRACT: Non-syndromic arthrogryposis multiplex congenita (AMC) is characterized by multiple congenital contractures resulting from reduced fetal mobility. Genetic mapping and whole exome sequencing were performed in 31 multiplex and/or consanguineous undiagnosed AMC families. Although this approach identified known AMC genes, we here report pathogenic mutations in two new genes. Homozygous frameshift mutations in CNTNAP1 were found in four unrelated families. Patients showed a marked reduction in motor nerve conduction velocity (<10 m/sec) and transmission electron microscopy (TEM) of sciatic nerve in the index cases revealed severe abnormalities of both nodes of Ranvier width and myelinated axons. CNTNAP1 encodes CASPR, an essential component of node of Ranvier domains which underly saltatory conduction of action potentials along myelinated axons, an important process for neuronal function. A homozygous missense mutation in Adenylate Cyclase 6 gene (ADCY6) was found in another family characterized by a lack of myelin in the Peripheral Nervous System (PNS) as determined by TEM. Morpholino knockdown of the zebrafish orthologs led to severe and specific defects in peripheral myelin in spite of the presence of Schwann cells. ADCY6 encodes a protein that belongs to adenylate cyclase family responsible for the synthesis of cAMP. Elevation of cAMP can mimic axonal contact in vitro and upregulates myelinating signals. Our data indicate an essential and so far unknown role of ADCY6 in PNS myelination likely through the cAMP pathway. Mutations of genes encoding proteins of Ranvier domains or involved in myelination of Schwann cells are responsible for novel and severe human axoglial diseases.
    Human Molecular Genetics 12/2013; DOI:10.1093/hmg/ddt618 · 6.68 Impact Factor
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    ABSTRACT: Wolf-Hirschhorn syndrome (WHS) is associated with facial dysmorphism including high forehead, high nasal bridge, hypertelorism and severe mental retardation. WHS results from a 4p16.3 deletion. Only a small number of reports have been made on the prenatal ultrasound findings observed in WHS. Here we report our experience on 10 cases of WHS ascertained prenatally between 1983 and 2009 through the CEMC-Auvergne registry of congenital malformations. The assumption that a "Greek warrior helmet" facies is pathognomonic of WHS could lead to misdiagnosis. Other clinical findings such as severe and early onset intrauterine growth retardation, facial dysmorphism (high forehead, high nasal bridge, low-set ears, micrognathia, hypertelorism), atrial or ventricular septal defect, and renal dysplasia should help obstetricians to suspect the diagnosis of WHS prenatally. Birth Defects Research (Part A), 97:806-811, 2013. © 2013 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 12/2013; 97(12):806-11. DOI:10.1002/bdra.23194 · 2.21 Impact Factor
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    ABSTRACT: Anophthalmia and/or microphthalmia, pulmonary hypoplasia, diaphragmatic hernia, and cardiac defects are the main features of PDAC syndrome. Recessive mutations in STRA6, encoding a membrane receptor for the retinol-binding protein, have been identified in some cases with PDAC syndrome, although many cases have remained unexplained. Using whole-exome sequencing, we found that two PDAC-syndrome-affected siblings, but not their unaffected sibling, were compound heterozygous for nonsense (c.355C>T [p.Arg119(∗)]) and frameshift (c.1201_1202insCT [p.Ile403Serfs(∗)15]) mutations in retinoic acid receptor beta (RARB). Transfection studies showed that p.Arg119(∗) and p.Ile403Serfs(∗)15 altered RARB had no transcriptional activity in response to ligands, confirming that the mutations induced a loss of function. We then sequenced RARB in 15 subjects with anophthalmia and/or microphthalmia and at least one other feature of PDAC syndrome. Surprisingly, three unrelated subjects with microphthalmia and diaphragmatic hernia showed de novo missense mutations affecting the same codon; two of the subjects had the c.1159C>T (Arg387Cys) mutation, whereas the other one carried the c.1159C>A (p.Arg387Ser) mutation. We found that compared to the wild-type receptor, p.Arg387Ser and p.Arg387Cys altered RARB induced a 2- to 3-fold increase in transcriptional activity in response to retinoic acid ligands, suggesting a gain-of-function mechanism. Our study thus suggests that both recessive and dominant mutations in RARB cause anophthalmia and/or microphthalmia and diaphragmatic hernia, providing further evidence of the crucial role of the retinoic acid pathway during eye development and organogenesis.
    The American Journal of Human Genetics 09/2013; DOI:10.1016/j.ajhg.2013.08.014 · 10.99 Impact Factor
  • Annales d Endocrinologie 09/2013; 74(4):281. DOI:10.1016/j.ando.2013.07.131 · 0.66 Impact Factor
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    ABSTRACT: With the introduction of array comparative genomic hybridization (aCGH) techniques in the diagnostic setting of patients with developmental delay and congenital malformations, many new microdeletion syndromes have been recognized. One of these recently recognized microdeletion syndromes is the 16p11.2 deletion syndrome, associated with variable clinical outcomes including developmental delay, autism spectrum disorder, epilepsy, and obesity, but also apparently normal phenotype. We report on a 16-year-old patient with developmental delay, exhibiting retinis pigmentosa with progressive visual failure from the age of 9 years, ataxia, and peripheral neuropathy. Chromosomal microarray analysis identified a 1.7-Mb 16p11.2 deletion encompassing the 593-kb common deletion (∼29.5 to ∼30.1 Mb; Hg18) and the 220-kb distal deletion (∼28.74 to ∼28.95 Mb; Hg18) that partially included the CLN3 gene. As the patient's clinical findings were different from usual 16p11.2 microdeletion phenotypes and showed some features reminiscent of juvenile neuronal ceroid-lipofuscinosis (JNCL, Batten disease, OMIM 204200), we suspected and confirmed a mutation of the remaining CLN3 allele. This case further illustrates that unmasking of hemizygous recessive mutations by chromosomal deletion represents one explanation for the phenotypic variability observed in chromosomal deletion disorders.European Journal of Human Genetics advance online publication, 17 July 2013; doi:10.1038/ejhg.2013.141.
    European journal of human genetics: EJHG 07/2013; 22(3). DOI:10.1038/ejhg.2013.141 · 4.23 Impact Factor
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    ABSTRACT: X-linked agammaglobulinemia (XLA) or Bruton disease is a relatively rare constitutionally immune disorder due to a genetic mutation of BTK (Bruton Tyrosin Kinase) gene which encodes for BTK protein. BTK is a signal-transducing protein expressed in hematopoietic lineages. The genetic disorder is responsible of B cells lymphocytes maturation arrest. The humoral immunodeficiency caused by BTK mutation is linked with recurrent bacterial and viral infections. Genetic investigations of prepositus as well as the other members of the family are necessary to characterize a mutation in BTK gene to confirm the diagnosis and reveal a hereditary transmission or de novo mutation. Authors propose and comment a case report of an 8 month aged child who suffers of Bruton disease. Initial presentation was neutropenia, genetic investigation has revealed a previously non-reported mutation in the BTK gene. The same mutation was found in the mother with low expression of BTK in monocytes and normal in B-cells suggesting a lineage specific extinction of BTK which has never been reported before.
    Gene 06/2013; 527(1). DOI:10.1016/j.gene.2013.05.070 · 2.08 Impact Factor
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    ABSTRACT: Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS). KS is defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Mutations in any of the nine genes identified to date account for only 30% of the KS cases. KS can be either isolated or associated with a variety of other symptoms, including deafness. This study reports SOX10 loss-of-function mutations in approximately one-third of KS individuals with deafness, indicating a substantial involvement in this clinical condition. Study of SOX10-null mutant mice revealed a developmental role of SOX10 in a subpopulation of glial cells called olfactory ensheathing cells. These mice indeed showed an almost complete absence of these cells along the olfactory nerve pathway, as well as defasciculation and misrouting of the nerve fibers, impaired migration of GnRH cells, and disorganization of the olfactory nerve layer of the olfactory bulbs.
    The American Journal of Human Genetics 05/2013; 92(5):707-24. DOI:10.1016/j.ajhg.2013.03.024 · 10.99 Impact Factor
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    ABSTRACT: The association of marfanoid habitus (MH) and intellectual disability (ID) has been reported in the literature, with overlapping presentations and genetic heterogeneity. A hundred patients (71 males and 29 females) with a MH and ID were recruited. Custom-designed 244K array-CGH (Agilent®; Agilent Technologies Inc., Santa Clara, CA) and MED12, ZDHHC9, UPF3B, FBN1, TGFBR1 and TGFBR2 sequencing analyses were performed. Eighty patients could be classified as isolated MH and ID: 12 chromosomal imbalances, 1 FBN1 mutation and 1 possibly pathogenic MED12 mutation were found (17%). Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%). These results suggest either that there are more loci with genes yet to be discovered or that MH can also be a relatively non-specific feature of patients with ID. The search for aortic complications is mandatory even if MH is associated with ID since FBN1 mutations or rearrangements were found in some patients. The excess of males is in favour of the involvement of other X-linked genes. Although it was impossible to make a diagnosis in 80% of patients, these results will improve genetic counselling in families.
    Clinical Genetics 03/2013; DOI:10.1111/cge.12094 · 3.65 Impact Factor
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    ABSTRACT: Asphyxiating Thoracic Dysplasia (ATD) belongs to the short rib polydactyly group and is characterized by a narrow thorax, short long bones and trident acetabular roof. Other reported features include polydactyly, renal, liver and retinal involvement. To date, mutations in IFT80, DYNC2H1, TTC21B and WDR19 have been reported in ATD. The clinical and molecular heterogeneity leads to difficulties in the evaluation of the long-term prognosis. We investigated 53 ATD cases (23 living cases and 30 fetuses) from 39 families. They benefited from a combined approach of deep phenotyping and IFT80 and DYNC2H1 molecular screening. Among the 23 postnatal cases, pulmonary insufficiency was noted in 60% of cases, with tracheotomy requirement in five cases. Renal and liver diseases occurred respectively in 17% and 22% of cases, whereas retinal alteration was present in 50% of cases aged more than 5 years. We identified DYNC2H1 mutations in 23 families (59%) and IFT80 mutations in two families (5%). However, in six families, only one heterozygote mutation in either IFT80 or DYNC2H1 was identified. Finally, the two genes were excluded in 14 families (36%). We conclude that DYNC2H1 is a major gene responsible for ATD, while IFT80 is rarely involved. The presence of only one mutation in six families and the exclusion of the two genes in 14 families support the involvement of other causal cilia genes. The long-term follow up emphasizes that the pulmonary prognosis is probably less pejorative and retinal involvement more frequent than previously thought.
    Journal of Medical Genetics 02/2013; 50(2):91-8. DOI:10.1136/jmedgenet-2012-101282 · 5.64 Impact Factor
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    ABSTRACT: Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia and Rad3-related (ATR) kinases are two key regulators of DNA-damage responses (DDR) that are mainly activated in response to DNA double-strand breaks and single-stranded DNA damages, respectively. Seckel Syndrome, a rare genetic disorder characterized by a microcephaly and a markedly reduced body size, has been associated with defective ATR-dependent DNA damage signalling. However, the only human genetic ATR defect reported so far is a hypomorphic splicing mutation identified in five related individuals with Seckel syndrome. Here, we report the first case of primary microcephaly with compound heterozygous mutations in ATR: a 540kb genomic deletion on one allele and a missense mutation leading to splice dysregulation on the other which ultimately lead to a sharp decrease in ATR expression. DNA combing technology revealed a profound spontaneous alteration of several DNA replication parameters in patient's cells and FISH analyses highlighted the genomic instability caused by ATR deficiency. Collectively, our results emphasize the crucial role for ATR in the control of DNA replication, and reinforce the complementary and non redundant contributions of ATM and ATR in human cells to face DNA damages and warrant genome integrity.
    Human Mutation 02/2013; 34(2). DOI:10.1002/humu.22245 · 5.05 Impact Factor
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    ABSTRACT: Microdeletions of 8q21.3-8q22.1 have been identified in all patients with Nablus mask-like facial syndrome (NMLFS). A recent report of a patient without this specific phenotype presented a 1.6 Mb deletion in this region that partially overlapped with previously reported 8q21.3 microdeletions, thus restricting critical region for this syndrome. We report on another case of an 8q21.3 deletion revealed by array comparative genome hybridization (aCGH) in a 4-year-old child with global developmental delay, autism, microcephaly, but without Nablus phenotype. The size of the interstitial deletion was estimated to span 5.2 Mb. By combining the data from previous reports on 8q21.3-8q22.1 deletions and our case, we were able to narrow the critical region of Nablus syndrome to 0.5 Mb. The deleted region includes FAM92A1, which seems to be a potential candidate gene in NMLFS. © 2012 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 01/2013; 161A(1). DOI:10.1002/ajmg.a.35614 · 2.05 Impact Factor

Publication Stats

1k Citations
214.20 Total Impact Points

Institutions

  • 2013–2015
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France
  • 1999–2014
    • Centre Hospitalier Universitaire de Clermont-Ferrand
      • Pôle Gynécologie obstétrique et reproduction humaine (GORH)
      Clermont, Auvergne, France
  • 2008–2009
    • Académie de Clermont-Ferrand
      Clermont, Picardie, France
  • 2006
    • Université de Rennes 1
      Roazhon, Brittany, France
    • University of Auvergne
      Clermont, Auvergne, France
  • 2005–2006
    • Université de Rennes 2
      Roazhon, Brittany, France
  • 2004–2005
    • Polytech Clermont-Ferrand
      Auvergne, France