Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation.
ABSTRACT Noonan syndrome (NS) is an autosomal dominant disorder comprising short stature, facial dysmorphism, short and/or webbed neck, heart defects, and cryptorchidism in males. The gene responsible for the disorder (PTPN11) was recently identified, and explains 30-50% of the cases clinically diagnosed as NS. Cardiofaciocutaneous (CFC) syndrome, a similar but distinct entity, is characterized by relative macrocephaly, characteristic facial appearance, ectodermal abnormalities (sparse and friable hair, sparse eyebrows, hyperkeratotic skin), congenital heart defects, and growth and mental retardation. We describe on a young woman who presents clinical features of NS (short stature, triangular facies, with downslanting palpebral fissures and apparent hypertelorism, webbed neck, pulmonary stenosis, bleeding diathesis, prominent corneal nerves), but with a more prominent ectodermal involvement (sparse and very coarse hair, sparse eyebrows and eyelashes) and developmental delay/mental retardation, which are characteristic of CFC patients. Sequencing of the PTPN11 gene showed a T411M substitution, not previously described in patients with NS. The same mutation was found in her mother and older sister, not initially considered to be affected by NS, but with very subtle clinical findings compatible with this diagnosis. Molecular dynamic studies indicate that this new mutation, similar to other previously described mutations, favors a more active protein conformation. However, the main disruptive effect is not directly in the catalytic domain, suggesting that the location of this mutation could make the protein more susceptible to gene-gene or gene-environment interactions. Atypical cases of NS should be screened for mutations in the PTPN11 gene and in the case of a positive result, first-degree relatives should also be tested for the specific mutation.
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ABSTRACT: The Anatomical collection of the Department of Anatomy and Cell Biology, Medical School of the University of Halle, Germany, comprises more than 8,000 specimens. Around 600 of them show congenital anomalies. The collection of abnormal human and animal fetuses began as the private collection of Johann Friedrich Meckel the Elder (1724-1774), his son Philipp Friedrich Theodor Meckel (1755-1803) and his grandson Johann Friedrich Meckel the Younger (1781-1833). Meckel the Younger founded the systematic science of developmental pathology. Radiographical techniques, computer tomographic (CT) methods, magnetic resonance imaging (MRI), and comparative genomic hybridization (CGH) were used to diagnose abnormal human fetuses in the Meckel-anatomical collections. Cystic hygroma colli was found in five of the human fetuses originally described by JF Meckel the Younger in 1826 and one of his students in 1819 [Hencke, 1819]. CGH analyses were used to test whether the observed cystic hygroma colli could be caused by chromosomal aneuploidies. CGH-ratio profiles of all chromosomes were apparently normal. PCR-based sex determination tests on ancient DNA were used to determine the fetal gonosomal constitution. It is likely that the Meckel specimens are among the oldest fetuses in which Ullrich-Turner "phenotype" has been diagnosed.American Journal of Medical Genetics Part A 01/2007; 143(2):119-28. DOI:10.1002/ajmg.a.31488 · 2.05 Impact Factor
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ABSTRACT: The concept of neuro-cardio-facio-cutaneous (NCFC) syndrome has recently been formulated in order to bring together a number of hereditary diseases that include a number of shared phenotypic features to differing degrees: (i) craniofacial dysmorphia; (ii) delayed growth; (iii) mental retardation or learning difficulties; (iv) cardiac malformations (most commonly pulmonary valve stenosis and hypertrophic cardiomyopathy); (v) cutaneous anomalies, and in some cases, predisposition to certain forms of malignant solid tumors and blood diseases, associated at the physiopathological level with deregulation of the Ras-MAP kinase cellular signaling pathways 1. NCFC subsumes neurofibromatosis type1, Legius syndrome, LEOPARD syndrome, Noonan syndrome, Costello syndrome and cardiofaciocutaneous (CFC) syndrome. While the majority of these diseases are readily distinguishable in clinical terms, with or without diagnostic criteria, none of them have any pathognomonic signs. Many cases attest to the strong clinical homologies and forms of overlapping between these different diseases. In recent years, the discovery of germinal mutations of these different diseases has in fact reinforced the unifying clinical and biochemical concept of NCFC syndrome.Annales de Dermatologie et de Vénéréologie 138(6-7):483-93. · 0.67 Impact Factor
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ABSTRACT: In this work a sliding mode controller solution is proposed for tracking problems associated to well known types of mobile robots. The robustness property of the sliding mode controller for the continuous-time systems can thus be extended to the discrete-time systems under others conditions for existence sliding modes. Simulation results are presented to illustrate the effectiveness of the approach in two cases continuous-time and discrete-time.Control, Communications and Signal Processing, 2004. First International Symposium on; 02/2004