Wells C.,Service dhistologie |
Loundon N.,Service dORL |
Garabedian N.,Service dORL |
Wiener-Vacher S.,Service dORL |
And 5 more authors.
European Journal of Medical Genetics | Year: 2016
CHARGE syndrome (MIM#. 214800) (Coloboma, Heart defect, Atresia of choanae, Retarded growth and development, Genital hypoplasia, Ear abnormalities/deafness) is caused by heterozygous mutation of CHD7 transmitted in an autosomal dominant manner. In this report, we describe a patient with bilateral hearing impairment, unusually-shaped ears, no intellectual disability and a patent ductus arteriosus. Further investigation showed abnormal semicircular canals and the presence of olfactory bulbs. He does not fulfill the Blake or the Verloes criteria for CHARGE. A de novo mutation at the donor splice site of intron 33 was identified (c.7164 + 1G > A). It is of importance to diagnose mildly affected patients for appropriate genetic counselling and to better understand the mild end of the phenotypic spectrum of CHARGE syndrome. © 2016 Elsevier Masson SAS.
Dupont C.,Unite de Cytogenetique |
Grati F.R.,TOMA Advanced Biomedical Assays S.p.A. |
Choy K.W.,Chinese University of Hong Kong |
Jaillard S.,Hopital University Of Pontchaillou |
And 18 more authors.
Prenatal Diagnosis | Year: 2015
What's already known about this topic?Fluorescence in situ hybridization analysis of the 22q11.2 region in a large cohort of children referred for DiGeorge syndrome/velocardiofacial syndrome led to the identification of a new chromosomal syndrome:microduplication 22q11.2. This syndrome has a highly variable clinical phenotype. What does this study add?This study is the first prenatal series about the 22q11.2 microduplication syndrome (24 cases). We searched for possible correlations between fetal phenotypes, indications for invasive prenatal diagnosis, inheritance, pregnancy outcomes, and presence of others copy number variations. Objective: Microduplication 22q11.2 is primarily characterized by a highly variable clinical phenotype, which ranges from apparently normal or slightly dysmorphic features (in the presence or absence of learning disorders) to severe malformations with profound mental retardation. Hence, genetic counseling is particularly challenging when microduplication 22q11.2 is identified in a prenatal diagnosis. Here, we report on 24 prenatal cases of microduplication 22q11.2. Methods: Seventeen of the cases were also reanalyzed by microarray analysis, in order to determine copy number variations (CNVs, which are thought to influence expressivity). We also searched for possible correlations between fetal phenotypes, indications for invasive prenatal diagnosis, inheritance, and pregnancy outcomes. Results: Of the 24 cases, 15 were inherited, six occurred de novo, and three were of unknown origin. Termination of pregnancy occurred in seven cases and was mainly decided on the basis of ultrasound findings. Moreover, additional CNVs were found in some patients and we try to make a genotype-phenotype correlation. Conclusion: We discuss the complexity of genetic counseling for microduplication 22q11.2 and comment on possible explanations for the clinical heterogeneity of this syndrome. In particular, we assessed the co-existence of additional CNVs and their contribution to phenotypic variations in chromosome 22q11.2 microduplication syndrome. © 2014 John Wiley & Sons, Ltd.
Castronovo P.,University of Milan |
Delahaye-Duriez A.,Service dhistologie |
Delahaye-Duriez A.,University of Paris 13 |
Gervasini C.,University of Milan |
And 8 more authors.
Clinical Genetics | Year: 2010
Castronovo P, Delahaye-Duriez A, Gervasini C, Azzollini J, Minier F, Russo S, Masciadri M, Selicorni A, Verloes A, Larizza L. Somatic mosaicism in Cornelia de Lange syndrome: a further contributor to the wide clinical expressivity?Cornelia de Lange syndrome (CdLS) is a rare, congenital syndrome characterized by growth retardation, dysmorphic face, mental retardation and limb reduction defects. Clinical manifestations of CdLS can be extremely variable. Mutations in NIPBL, SMC1A and SMC3 genes, encoding for a regulator and two subunits of the cohesin complex, respectively, are found in 60-65% of CdLS patients. We report on a male with CdLS who is mosaic for the c.2827delA mutation in the NIPBL gene. Allele quantitation by pyrosequencing showed the presence of the mutation in about 10% and 33% of DNA samples from peripheral blood and buccal smears, respectively. The patient shows a complex phenotype: growth and psychomotor retardation are characteristic of the severe forms of CdLS, while the absence of severe limb reduction defects and major malformations are typical of the mild phenotype. He also has depigmentation areas following Blashko lines, an unusual finding in CdLS, which has been associated with mosaicism in other genetic conditions. This case represents the first evidence of somatic mosaicism in CdLS and explains the mild phenotype in the patient as compared to that predicted by a truncating mutation. Besides confirming the clinical and genetic heterogeneity of CdLS, this case also raises the likely underestimated mutation rate of known genes and points to the complexity of addressing genotype-phenotype correlations. © 2010 John Wiley & Sons A/S.
Benammar A.,Service dhistologie |
Sermondade N.,Service dhistologie |
Sermondade N.,University of Paris 13 |
Faure C.,Service dhistologie |
And 9 more authors.
Gynecologie Obstetrique Fertilite | Year: 2012
Miscarriage concerns approximately 15% of pregnancies and recurrent fetal loss (RFL) constitute a particular situation concerning approximately 1% of women. The etiologic inquiry is often disappointing. Nutritional factors represent a promising aspect, insufficiently investigated even if numerous studies underline their impact on fertility, gametogenesis, embryonic development and pregnancies outcome. Obesity is considered as an independent risk factor for miscarriage, involved in oocyte and embryo quality, but also in endometrial receptivity. The male part involved in miscarriage was for a long time underestimated, neglecting the role of sperm in embryo development. If conventional sperm analysis remains essential, new investigations have to be considered such as sperm DNA or oxidant stress evaluation. It is particularly important to take into account nutritional factors as favoring miscarriage because they represent a flexible factor on which intervention is possible to improve pregnancy outcome, with toxics eviction and recommendations for diversified and well-balanced food. At last, effects of nutritional complements for miscarriage prevention remain controversial. © 2011 Elsevier Masson SAS. All rights reserved.