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Goldenberg A.,French Institute of Health and Medical Research | Riccardi F.,Hopital de la Timone EnfantAssistance publique hopitaux de MarseilleMarseilleFrance | Tessier A.,French Institute of Health and Medical Research | Pfundt R.,Afdeling GeneticaRadboud universitair medisch centrumNijmegen | And 31 more authors.
American Journal of Medical Genetics, Part A | Year: 2016

KBG syndrome, due to ANKRD11 alteration is characterized by developmental delay, short stature, dysmorphic facial features, and skeletal anomalies. We report a clinical and molecular study of 39 patients affected by KBG syndrome. Among them, 19 were diagnosed after the detection of a 16q24.3 deletion encompassing the ANKRD11 gene by array CGH. In the 20 remaining patients, the clinical suspicion was confirmed by the identification of an ANKRD11 mutation by direct sequencing. We present arguments to modulate the previously reported diagnostic criteria. Macrodontia should no longer be considered a mandatory feature. KBG syndrome is compatible with autonomous life in adulthood. Autism is less frequent than previously reported. We also describe new clinical findings with a potential impact on the follow-up of patients, such as precocious puberty and a case of malignancy. Most deletions remove the 5'end or the entire coding region but never extend toward 16q telomere suggesting that distal 16q deletion could be lethal. Although ANKRD11 appears to be a major gene associated with intellectual disability, KBG syndrome remains under-diagnosed. NGS-based approaches for sequencing will improve the detection of point mutations in this gene. Broad knowledge of the clinical phenotype is essential for a correct interpretation of the molecular results. © 2016 Wiley Periodicals, Inc.


Schaefer E.,Hopitaux Universitaires Of Strasbourg | Durand M.,Hopitaux Universitaires Of Strasbourg | Stoetzel C.,French Institute of Health and Medical Research | Doray B.,Hopitaux Universitaires Of Strasbourg | And 17 more authors.
European Journal of Medical Genetics | Year: 2011

Hydrometrocolpos and polydactyly diagnosed in the prenatal period or early childhood may raise diagnostic dilemmas especially in distinguishing McKusick-Kaufman syndrome (MKKS) and the Bardet-Biedl syndrome (BBS). These two conditions can initially overlap. With time, the additional features of BBS appearing in childhood, such as retinitis pigmentosa, obesity, learning disabilities and progressive renal dysfunction allow clear differentiation between BBS and MKKS. Genotype overlap also exists, as mutations in the MKKS-BBS6 gene are found in both syndromes. We report 7 patients diagnosed in the neonatal period with hydrometrocolpos and polydactyly who carry mutations in various BBS genes (BBS6, BBS2, BBS10, BBS8 and BBS12), stressing the importance of wide BBS genotyping in patients with this clinical association for diagnosis, prognosis and genetic counselling. © 2010 Elsevier Masson SAS.


Houeijeh A.,Service de Genetique clinique Guy Fontaine | Andrieux J.,Laboratoire Of Genetique | Saugier-Veber P.,University of Rouen | David A.,Nantes University Hospital Center | And 16 more authors.
European Journal of Medical Genetics | Year: 2011

Thrombocytopenia-absent radius Syndrome (TAR) is a rare congenital malformation syndrome of complicated transmission. 1q21.1 deletion is necessary but not sufficient for its expression. We report the result of a French multicentric clinical study, and we emphasized on the role of the associated 1q21.1 deletion in the diagnosis and the genetic counselling of our patients. We gathered information on 14 patients presenting with TAR syndrome and referred for genetic counselling in six different university hospitals (8 foetuses, 1 child and 5 adults). Clinical or pathology details, as well as skeletal X-rays were analyzed. Genetic studies were performed by Array-CGH, and Quantitative Multiplex PCR. We demonstrated the very variable phenotypes of TAR syndrome. Female:male ratio was ∼2:1. All patients presented with bilateral radial aplasia/hypoplasia with preserved thumbs. Phocomelia and lower limb anomalies were present in 28% of the cases. We reported the first case of cystic hygroma on affected foetus. 1q21.1 deletions ranging from 330 to 1100 kb were identified in all affected patients. Most of them were inherited from one healthy parent (80%). The identification of a 1q21.1 deletion allowed confirmation of TAR syndrome diagnosis, particularly in foetuses and in atypical phenotypes. Additionally, it allowed accurate genetic counselling, especially when it occurred de novo. These findings allowed discussing the diagnostic criteria and management towards TAR syndrome. © 2011 Elsevier Masson SAS.


PubMed | TU Dresden, Service de Genetique Clinique Guy Fontaine, Prof Dr Alex Obregia Clinical Hospital Of Psychiatry, Laboratoire Of Genetique Medicale and Victor Babes National Institute of Pathology
Type: Case Reports | Journal: European journal of medical genetics | Year: 2015

We report on the clinical data and molecular cytogenetic findings in three unrelated patients presenting with intellectual disability and behavior abnormalities. An overlapping microduplication involving 3p26.2-26.3 was identified in these patients. All three aberrations were confirmed and proven to be parentally inherited. The sizes of the duplications were different, with a common minimal region of 423,754bp containing two genes - TRNT1 and CRBN. Here, we hypothesize that the copy number gain of CRBN gene might be responsible for developmental delay/intellectual disability.


Papuc S.M.,Victor Babes National Institute of Pathology | Hackmann K.,TU Dresden | Andrieux J.,Laboratoire Of Genetique Medicale | Vincent-Delorme C.,Service de Genetique Clinique Guy Fontaine | And 6 more authors.
European Journal of Medical Genetics | Year: 2015

We report on the clinical data and molecular cytogenetic findings in three unrelated patients presenting with intellectual disability and behavior abnormalities. An overlapping microduplication involving 3p26.2-26.3 was identified in these patients. All three aberrations were confirmed and proven to be parentally inherited. The sizes of the duplications were different, with a common minimal region of 423,754bp containing two genes - TRNT1 and CRBN. Here, we hypothesize that the copy number gain of CRBN gene might be responsible for developmental delay/intellectual disability. © 2015 Elsevier Masson SAS.

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