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author:("route, moelle")
1.  Early-Onset Osteoarthritis, Charcot-Marie-Tooth Like Neuropathy, Autoimmune Features, Multiple Arterial Aneurysms and Dissections: An Unrecognized and Life Threatening Condition 
PLoS ONE  2014;9(5):e96387.
Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined.
All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases.
Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren’s disease, rheumatoid arthritis, Hashimoto’s disease, or isolated autoantibodies- were found in 36% of patients.
SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.
PMCID: PMC4012990  PMID: 24804794
2.  Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes 
Nature genetics  2010;42(7):619-625.
Joubert syndrome (JBTS), related disorders (JSRD) and Meckel syndrome (MKS) are ciliopathies. We now report that MKS2 and JBTS2 loci are allelic and due to mutations in TMEM216, encoding an uncharacterized tetraspan transmembrane protein. JBTS2 patients displayed frequent nephronophthisis and polydactytly, and two cases conformed to the Oro-Facio-Digital type VI phenotype, whereas skeletal dysplasia was common in MKS fetuses. A single p.R73L mutation was identified in all patients of Ashkenazi Jewish descent (n=10). TMEM216 localized to the base of primary cilia, and loss of TMEM216 in patient fibroblasts or following siRNA knockdown caused defective ciliogenesis and centrosomal docking, with concomitant hyperactivation of RhoA and Dishevelled. TMEM216 complexed with Meckelin, encoded by a gene also mutated in JSRD and MKS. Abrogation of tmem216 expression in zebrafish led to gastrulation defects that overlap with other ciliary morphants. The data implicate a new family of proteins in the ciliopathies, and further support allelism between ciliopathy disorders.
PMCID: PMC2894012  PMID: 20512146
3.  Long-term outcome of children born after a first-trimester measurement of nuchal translucency at the 99th percentile or greater with normal karyotype: a prospective study 
To assess the long term outcome of children born following a first trimester measurement of nuchal translucency (NT) ≥ 99th centile during routine first trimester screening in an unselected population.
Study design
162 infants were born alive. Clinical examination as well as a questionnaire to the parents (Ages and Stages Questionnaires (ASQ)) at the age of 2 were obtained in 160 children. Our study population was compared to an external control group made of the 370 full-term control children.
The prevalence of abnormal clinical pediatric examination and ASQ results at 2 years were not associated with NT thickness. Comparison with an external control group did not demonstrate an increased incidence of developmental delay.
Parents should be informed that when the fetus is shown to be normal by ultrasound at 22–24 weeks of gestation the risk of adverse neonatal outcome or developmental delay in early childhood is not increased.
PMCID: PMC1933588  PMID: 17240232
Child, Preschool; Cohort Studies; Developmental Disabilities; epidemiology; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Karyotyping; Nuchal Translucency Measurement; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Questionnaires; Time Factors; Unselected population; First trimester screening; Nuchal translucency; Normal karyotype; Long term follow-up

Results 1-3 (3)