53 research outputs found
Finger creases lend a hand in Kabuki syndrome.
International audienceKabuki syndrome (KS) is a rare syndrome associating malformations with intellectual deficiency and numerous visceral, orthopedic, endocrinological, immune and autoimmune complications. The early establishment of a diagnostic of KS leads to better care of the patients and therefore prevents complications such as perception deafness, severe complications of auto-immune diseases or obesity. However, the diagnosis of KS remains difficult because based on the appreciation of facial features combined with other highly variable features. We describe a novel sign, namely the attenuation and/or congenital absence of the IPD crease of the third and fourth fingers associated with limitation of flexion of the corresponding joints, which seems to be specific of KS and could help the clinician to diagnose KS
Fifteen years of research on oralâfacialâdigital syndromes: from 1 to 16 causal genes
Oralâfacialâdigital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in the OFD1 gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3, TMEM107, INTU, KIAA0753 and IFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42, TMEM138, TMEM231 and WDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype
Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing
A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing
Purpose
Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the âClinVar low-hanging fruitâ reanalysis, reasons for the failure of previous analyses, and lessons learned.
Methods
Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted.
Results
We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency).
Conclusion
The âClinVar low-hanging fruitâ analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock
EpidĂ©miologie, clinique, gĂ©nĂ©tique et prĂ©vention des malformations congĂ©nitales : registre des malformations congĂ©nitales dâAlsace 1995-2009
The Registry of congenital malformations of Alsace is one of the five registries of congenital malformations of metropolitan France. As a member of EUROCAT network, it provides a continuous registration for congenital malformations and chromosome abnormatities among the 23,000 annual births recorded in the two departments of Alsace (corresponding to approximately 3% of all births in France).This system is a crucial tool for clinical, epidemiological and public health studies.Our study concerns the 15-year period 1995-2009 period, marked by a major development of fetal medicine and prenatal diagnosis. The total prevalence of congenital malformations is 3.6%. The 6,845 registered cases are divided into 80.3% of livebirths, 18.7% terminations of pregnancy and 1% of stillbirths. The study emphasizes an increasing rate of prenatal diagnosis from 26.1% in 1995 to 46.5% in 2009. The study about orofacial clefts demonstrates these advances in prenatal diagnosis with increasing detection rates from 43% (1995-1999) to 53% (2000-2004) and 66% (2005-2009).This period is also marked by an important evolution in the field of medical practices, including the setting-up of multidisciplinar centres of prenatal diagnosis which contribute to an easier diffusion of knowledge between professionals.Le Registre de malformations congĂ©nitales dâAlsace constitue lâun des cinq registres de malformations congĂ©nitales de France mĂ©tropolitaine. Membre du rĂ©seau europĂ©en EUROCAT, il gĂ©nĂšre un enregistrement continu et exhaustif des malformations congĂ©nitales parmi les 23 000 naissances annuelles recensĂ©es dans les deux dĂ©partements dâAlsace (ce qui correspond Ă approximativement 3% de lâensemble des naissances en France). Ses objectifs sâinscrivent dans une triple dĂ©marche clinique, Ă©pidĂ©miologique et de santĂ© publique.Notre Ă©tude sâest intĂ©ressĂ©e Ă pĂ©riode 1995-2009, marquĂ©e par un dĂ©veloppement majeur de la mĂ©decine foetale et du diagnostic prĂ©natal. La prĂ©valence totale des malformations congĂ©nitales est de 3,6% des naissances. Les 6 845 cas enregistrĂ©s se rĂ©partissent en 80,3% dâenfants nĂ©s vivants, 18,7% dâinterruptions mĂ©dicales de grossesse (IMG) et 1% de morts foetales in utero. Les quinze annĂ©es de lâĂ©tude sont marquĂ©es par une augmentation progressive du taux global de diagnostic prĂ©natal, de 26,1% en 1995 Ă 46,5% en 2009. LâĂ©tude concernant les fentes oro-faciales le dĂ©montre avec un taux passant de 43% en 1995-1999, Ă 53% en 2000-2004 et 66% en 2005-2009. Cette pĂ©riode voit Ă©galement Ă©voluer les pratiques mĂ©dicales avec la crĂ©ation des centres pluridisciplinaires de diagnostic prĂ©natal dont la multidisciplinaritĂ© favorise la diffusion du savoir parmi les professionnels pour une meilleure prise en charge des grossesses
Epidemiology, genetics and prevention of congenital malformations : registry of congenital malformations of Alsace, France 1995-2009
Le Registre de malformations congĂ©nitales dâAlsace constitue lâun des cinq registres de malformations congĂ©nitales de France mĂ©tropolitaine. Membre du rĂ©seau europĂ©en EUROCAT, il gĂ©nĂšre un enregistrement continu et exhaustif des malformations congĂ©nitales parmi les 23 000 naissances annuelles recensĂ©es dans les deux dĂ©partements dâAlsace (ce qui correspond Ă approximativement 3% de lâensemble des naissances en France). Ses objectifs sâinscrivent dans une triple dĂ©marche clinique, Ă©pidĂ©miologique et de santĂ© publique.Notre Ă©tude sâest intĂ©ressĂ©e Ă pĂ©riode 1995-2009, marquĂ©e par un dĂ©veloppement majeur de la mĂ©decine foetale et du diagnostic prĂ©natal. La prĂ©valence totale des malformations congĂ©nitales est de 3,6% des naissances. Les 6 845 cas enregistrĂ©s se rĂ©partissent en 80,3% dâenfants nĂ©s vivants, 18,7% dâinterruptions mĂ©dicales de grossesse (IMG) et 1% de morts foetales in utero. Les quinze annĂ©es de lâĂ©tude sont marquĂ©es par une augmentation progressive du taux global de diagnostic prĂ©natal, de 26,1% en 1995 Ă 46,5% en 2009. LâĂ©tude concernant les fentes oro-faciales le dĂ©montre avec un taux passant de 43% en 1995-1999, Ă 53% en 2000-2004 et 66% en 2005-2009. Cette pĂ©riode voit Ă©galement Ă©voluer les pratiques mĂ©dicales avec la crĂ©ation des centres pluridisciplinaires de diagnostic prĂ©natal dont la multidisciplinaritĂ© favorise la diffusion du savoir parmi les professionnels pour une meilleure prise en charge des grossesses.The Registry of congenital malformations of Alsace is one of the five registries of congenital malformations of metropolitan France. As a member of EUROCAT network, it provides a continuous registration for congenital malformations and chromosome abnormatities among the 23,000 annual births recorded in the two departments of Alsace (corresponding to approximately 3% of all births in France).This system is a crucial tool for clinical, epidemiological and public health studies.Our study concerns the 15-year period 1995-2009 period, marked by a major development of fetal medicine and prenatal diagnosis. The total prevalence of congenital malformations is 3.6%. The 6,845 registered cases are divided into 80.3% of livebirths, 18.7% terminations of pregnancy and 1% of stillbirths. The study emphasizes an increasing rate of prenatal diagnosis from 26.1% in 1995 to 46.5% in 2009. The study about orofacial clefts demonstrates these advances in prenatal diagnosis with increasing detection rates from 43% (1995-1999) to 53% (2000-2004) and 66% (2005-2009).This period is also marked by an important evolution in the field of medical practices, including the setting-up of multidisciplinar centres of prenatal diagnosis which contribute to an easier diffusion of knowledge between professionals
Epidemiology, genetics and prevention of congenital malformations : registry of congenital malformations of Alsace, France 1995-2009
Le Registre de malformations congĂ©nitales dâAlsace constitue lâun des cinq registres de malformations congĂ©nitales de France mĂ©tropolitaine. Membre du rĂ©seau europĂ©en EUROCAT, il gĂ©nĂšre un enregistrement continu et exhaustif des malformations congĂ©nitales parmi les 23 000 naissances annuelles recensĂ©es dans les deux dĂ©partements dâAlsace (ce qui correspond Ă approximativement 3% de lâensemble des naissances en France). Ses objectifs sâinscrivent dans une triple dĂ©marche clinique, Ă©pidĂ©miologique et de santĂ© publique.Notre Ă©tude sâest intĂ©ressĂ©e Ă pĂ©riode 1995-2009, marquĂ©e par un dĂ©veloppement majeur de la mĂ©decine foetale et du diagnostic prĂ©natal. La prĂ©valence totale des malformations congĂ©nitales est de 3,6% des naissances. Les 6 845 cas enregistrĂ©s se rĂ©partissent en 80,3% dâenfants nĂ©s vivants, 18,7% dâinterruptions mĂ©dicales de grossesse (IMG) et 1% de morts foetales in utero. Les quinze annĂ©es de lâĂ©tude sont marquĂ©es par une augmentation progressive du taux global de diagnostic prĂ©natal, de 26,1% en 1995 Ă 46,5% en 2009. LâĂ©tude concernant les fentes oro-faciales le dĂ©montre avec un taux passant de 43% en 1995-1999, Ă 53% en 2000-2004 et 66% en 2005-2009. Cette pĂ©riode voit Ă©galement Ă©voluer les pratiques mĂ©dicales avec la crĂ©ation des centres pluridisciplinaires de diagnostic prĂ©natal dont la multidisciplinaritĂ© favorise la diffusion du savoir parmi les professionnels pour une meilleure prise en charge des grossesses.The Registry of congenital malformations of Alsace is one of the five registries of congenital malformations of metropolitan France. As a member of EUROCAT network, it provides a continuous registration for congenital malformations and chromosome abnormatities among the 23,000 annual births recorded in the two departments of Alsace (corresponding to approximately 3% of all births in France).This system is a crucial tool for clinical, epidemiological and public health studies.Our study concerns the 15-year period 1995-2009 period, marked by a major development of fetal medicine and prenatal diagnosis. The total prevalence of congenital malformations is 3.6%. The 6,845 registered cases are divided into 80.3% of livebirths, 18.7% terminations of pregnancy and 1% of stillbirths. The study emphasizes an increasing rate of prenatal diagnosis from 26.1% in 1995 to 46.5% in 2009. The study about orofacial clefts demonstrates these advances in prenatal diagnosis with increasing detection rates from 43% (1995-1999) to 53% (2000-2004) and 66% (2005-2009).This period is also marked by an important evolution in the field of medical practices, including the setting-up of multidisciplinar centres of prenatal diagnosis which contribute to an easier diffusion of knowledge between professionals
Surveillance des grossesses exposées aux médicaments en France : les registres de malformations congénitales
Les registres de malformations congénitales ont été mis en place dans de nombreux pays
industrialisés à la suite du drame de la thalidomide. La France compte actuellement sept
registres de malformations congénitales qui assurent la surveillance épidémiologique
systématique des issues de grossesse. Ils font partie de réseaux internationaux de
registres de malformations, en particulier European surveillance of congenital
anomalies (EUROCAT). Si le développement des mesures de prévention, et en
particulier le diagnostic prénatal, a progressivement conduit les registres à tenir un
rĂŽle primordial dâĂ©valuation en population de lâimpact des politiques de santĂ© publique
dans le domaine de la pĂ©rinatalitĂ©, lâun des rĂŽles majeurs des registres de population
reste la dĂ©tection prĂ©coce de clusters de malformations, secondaires Ă lâintroduction dâun
nouvel agent tĂ©ratogĂšne dans lâenvironnement
Syndrome de Raine (à propos d'une observation familiale non létale de dysplasie ostéosclérotique)
STRASBOURG-Medecine (674822101) / SudocSudocFranceF
Le syndrome de Sotos (Etude d'une cohorte strasbourgeoise et revue de la littérature : des histoires de grands...)
STRASBOURG-Medecine (674822101) / SudocSudocFranceF
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