Hadj Salem I.,Laboratoire Of Genetique Moleculaire Humaine |
Kamoun F.,Service de Neuro pediatrie |
Louhichi N.,Laboratoire Of Genetique Moleculaire Humaine |
Mziou M.,Service de Neuro pediatrie |
And 4 more authors.
Bioscience Reports | Year: 2011
LGMD (limb-girdle muscular dystrophy) and CMD (congenital muscular dystrophy) are two common forms of neuromuscular disorders which are distinguishable by their age of onset but with probably a similar underlying pathway. In the present study, we report immunohistochemical, Western-blot and genetic analyses in a large consanguineous Tunisian family with two branches, including seven patients sharing similar LGMD2 phenotype in one branch and one CMD patient in the other branch. Linkage analyses were compatible with the LGMD2A locus in one branch and the MDC1A (muscular dystrophy congenital type 1A) locus in the other branch. This result was supported by deficiency in merosin and calpain3 in the CMD patient and LGMD patients respectively. Mutation analysis revealed two distinct mutations: a c.8005delT frameshift deletion in exon 56 of the LAMA2 (laminin-α2) gene (MDC1A) was found in the CMD patient and a new homozygous mutation C.1536+1G>T in the donor splice site of intron 12 of the CAPN3 (calpain3) gene (LGMD2A) was found in the LGMD patients. RT-PCR (reverse transcription-PCR) performed on total RNA from a LGMD2A patient's muscle biopsy showed complete retention of intron 12 in CAPN3 cDNA, generating a PTC (premature termination codon) that potentially elicits degradation of the nonsense mRNA by NMD (nonsense-mediated mRNA decay). Our results indicate that mRNA analysis is necessary to clarify the primary effect of genomic mutations on splicing efficiency that alters mRNA processing and expression level. ©The Authors Journal compilation ©2011 Biochemical Society.
Becker K.,TU Dresden |
Di Donato N.,TU Dresden |
Holder-Espinasse M.,Service de Genetique Clinique |
Andrieux J.,Institute Of Genetique Medicale |
And 12 more authors.
European Journal of Medical Genetics | Year: 2012
Interstitial 6q deletions can cause a variable phenotype depending on the size and location of the deletion. 6q14 deletions have been associated with intellectual disability and a distinct pattern of minor anomalies, including upslanted palpebral fissures with epicanthal folds, a short nose with broad nasal tip, anteverted nares, long philtrum, and thin upper lip. In this study we describe two patients with overlapping 6q14 deletions presenting with developmental delay and characteristic dysmorphism. Molecular karyotyping using array CGH analysis revealed a de novo 8.9 Mb deletion at 6q14.1-q14.3 and a de novo 11.3 Mb deletion at 6q12.1-6q14.1, respectively. We provide a review of the clinical features of twelve other patients with 6q14 deletions detected by array CGH analysis. By assessing all reported data we could not identify a single common region of deletion. Possible candidate genes in 6q14 for intellectual disability might be FILIP1, MYO6, HTR1B, and SNX14. © 2012 Elsevier Masson SAS.
Chouery E.,Saint - Joseph University |
Delague V.,French Institute of Health and Medical Research |
Jalkh N.,Saint - Joseph University |
Salem N.,Saint - Joseph University |
And 9 more authors.
Neurogenetics | Year: 2011
Dentoleukoencephalopathies with autosomal recessive inheritance are very rare. Recently, a large inbred Syrian pedigree was reported with oligodontia in association with a degenerative neurologic condition characterized by progressive ataxia and pyramidal syndrome and abnormalities in the white matter and cortical atrophy. A whole-genome screening of this family using 382 microsatellite markers was completed, but no evidence was found of linkage to any chromosomal region. A genome-wide linkage analysis using the 260K single nucleotide polymorphism Affymetrix array was then undertaken and a maximum multipoint logarithm of the odds score of 5.66 (NPL score∈=∈7.65) was detected on chromosome 10q22 region. This genomic interval contains 95 known genes including the Prosaposin gene (PSAP) responsible for metachromatic leukodystrophy, which was excluded. Seventeen additional candidate genes were tested and excluded. Sequencing of the whole candidate locus is in progress and should allow the identification of the causative gene in this rare disease, thereby improving the understanding of the physiopathology of this disease. © 2010 Springer-Verlag.
Besnard M.,Center Hospitalier Of Polynesie Francaise Chpf |
Eyrolle-Guignot D.,Service d'obstetrique |
Guillemette-Artur P.,Service de radiologie |
Lastere S.,Laboratoire Of Biologie Medicale |
And 9 more authors.
Eurosurveillance | Year: 2016
We detected an unusual increase in congenital cerebral malformations and dysfunction in fetuses and newborns in French Polynesia, following an epidemic of Zika virus (ZIKV), from October 2013 to March 2014. A retrospective review identified 19 cases, including eight with major brain lesions and severe microcephaly, six with severe cerebral lesions without microcephaly and five with brainstem dysfunction without visible malformations. Imaging revealed profound neurological lesions (septal and callosal disruption, ventriculomegaly, abnormal neuronal migration, cerebellar hypoplasia, occipital pseudocysts, brain calcifications). Amniotic fluid was drawn from seven cases at gestation weeks 20 to 29. ZIKV RNA was detected by RT-PCR and infectious ZIKV isolates were obtained in four of five microcephalic, but not in two non-microcephalic cases with severe brain lesions. Medical termination of pregnancy was performed in eleven cases; two cases with brainstem dysfunction died in the first months of life; six cases are alive, with severe neurological impairment. The results show that four of seven tested fetuses with major neurological injuries were infected with ZIKV in utero. For other non-microcephalic, congenital abnormalities we were not able to prove or exclude ZIKV infection retrospectively. The unusual occurrence of brain malformations or dysfunction without microcephaly following a ZIKV outbreak needs further studies. © 2016, European Centre for Disease Prevention and Control (ECDC). All Rights Reserved.
Roques G.,Service dHemato Oncologie Pediatrique |
Roques G.,Reims University Hospital Center |
Munzer M.,Reims University Hospital Center |
Barthez M.-A.C.,Service de Neuro pediatrie |
And 6 more authors.
Pediatric Blood and Cancer | Year: 2014
Objectives: To describe the clinical profile and the prevalence of severe congenital neutropenia (SCN) and HAX1 mutations, so-called Kostmann syndrome, in France. Study Design: Two pedigrees were identified from the French registry. Results: The study included five subjects (three males), which represent 0.7% of the 759 SCN cases registered in France. The age at diagnosis was 0.3 years (range: 0.1-1.2 years) and the median age at the last follow-up was 7.3 years (range: 1.2-17.8 years). A novel large homozygous deletion of the HAX1 gene (exons 2-5) was found in one pedigree; while, a homozygous frameshift mutation was identified in exon 3 (c.430dupG, p.Val144fs) in the second pedigree. Severe bacterial infections were observed in four patients, including two cases of sepsis, one case of pancolitis, a lung abscess, and recurrent cellulitis and stomatitis. During routine follow-up, the median neutrophil value was 0.16×109/L, associated with monocytosis (2×109/L). Bone marrow (BM) smears revealed a decrease of the granulocytic lineage with no mature myeloid cells above the myelocytes. One patient died at age 2 from neurological complications, while two other patients, including one who underwent a hematopoietic stem cell transplantation (HSCT) at age 5, are living with very severe neurological retardation. Conclusions: SCN with HAX1 mutations, is a rare sub type of congenital neutropenia, mostly observed in population from Sweden and Asia minor, associating frequently neurological retardation, when the mutations involved the B isoform of the protein. Pediatr Blood Cancer 2014;61:1041-1048. © 2014 Wiley Periodicals, Inc.
Megarbane A.,Saint - Joseph University |
Megarbane A.,Institute Jerome Lejeune |
Dorison N.,Institute Jerome Lejeune |
Rodriguez D.,Service de Neuro Pediatrie |
And 2 more authors.
American Journal of Medical Genetics, Part A | Year: 2010
We report on two sibs with an elongated face with reduced expression, microcephaly, strabismus, wide philtrum, mild joint laxity, thumbsign, bilateral foot drop, and fixed pes cavus, absent tendinous reflexes, an unsteady gait, quick fatigue, slightly diminished limb muscle strength more pronounced distally, abnormalities of cranial nerves III, IV, VII, and most probably VI, and slowness in ideation. Previously unknown findings referred to as the "fork sign" at the pontine level and the "bracket sign" at the mesencephalic level were documented by magnetic resonance imaging. Differential diagnoses and the possibility of a hitherto unreported syndrome are discussed. © 2010 Wiley-Liss, Inc.
Ben Abdallah Chabchoub R.,Service Route |
Riquet A.,Service Route |
Ramdane A.,Service Route |
Vallee L.,Service de neuro pediatrie |
Raccoussot S.,Service Route
Archives de Pediatrie | Year: 2015
Classical Lemierre syndrome is a rare and severe disease with thrombosis of the internal jugular vein and metastatic infections. We report on a case of Lemierre-like syndrome secondary to mastoiditis, with a favorable outcome, in a healthy infant presenting with torticollis. Early diagnosis and treatment with antibiotics are necessary to decrease mortality. © 2015 Elsevier Masson SAS.
PubMed | Service Route and Service de neuro pediatrie
Type: Case Reports | Journal: Archives de pediatrie : organe officiel de la Societe francaise de pediatrie | Year: 2015
Classical Lemierre syndrome is a rare and severe disease with thrombosis of the internal jugular vein and metastatic infections. We report on a case of Lemierre-like syndrome secondary to mastoiditis, with a favorable outcome, in a healthy infant presenting with torticollis. Early diagnosis and treatment with antibiotics are necessary to decrease mortality.