HUM-MOLGEN archive: DIAG: 8 messages/1 PT req./2 replies

************************************************************** HUM-MOLGEN DIAGnostics/Clinical Research ************************************************************** This DIAG message contains 8 submessage(s): 1) 23 mo little girl with a karyotype 46,XX,del(14)(q11.2 q13) 2) Mandibulo-Facial Dysostosis 3) Reply to Ricky Lewis: inv7 and OI 4) Lipodystrophy and OI II and III 5) familial myoclonus/ PT REQUEST 6) Gene therapy research for Fragile X syndrome 7) 12,4 translocation patient/reply to Eileen B 8) A-T study; req. for collaboration from Germany Carlo Gambacorti MD, Editor, Human Molecular Genetics network Diagnostics/Clinical Research Section ************************************************************** I am taking care of a 23 mo little girl with a karyotype 46,XX,del(14)(q11.2 q13). I would like to share information on this case with whomever has followed patients showing rearrangements within the same chromosomal region. Romeo Carrozzo, M.D. Servizio di Genetica Medica Ospedale San Raffaele c/o TIGEM Via Olgettina 58 20132 Milano Italy Tel +39 2 26437329 Fax +39 2 21560220 e-mail: carrozzo@tigem.it ************************************************************** Good Morning, I have seen a newborn white male with macrostomia, and bilateral preauricular tags appearing almost like inverse duplicated pinnae. His external auditory canals are present but small, particularly at the outer opening. His ear pinnae are normal otherwise. His palpebral fissures downslant slightly. His zygomatic arches are intact. His lid margins are normal and he has no extension of hair onto his face. He is normal below the neck. He is a behaviorally normal infant, but is not yet a month old. His mother is caucasian. Paternity is disputed, but the father may be of caucasian/asian mix. In a literature search, I have come across an article by Hunt and Smith from the early 1950's entitled 'Mandibulo-Facial Dysostosis'. The pictures in this article describe my patient exactly. Subsequent to that article, all references equate MFD with Treacher Collins Sydrome. Neither my patient nor the patient in the Hunt and Smith article has Treacher Collins syndrome. I would be grateful for any input that anyone might have on this apparent contridiction. Angela E. Scheuerle, M.D. Assistant Professor Division of Medical Genetics Department of Pediatrics UT Health Science Center - Houston 6431 Fannin, MSB 3.144 Houston TX 77030 ascheuer@ped1.med.uth.tmc.edu ************************************************************** In reply to Rick Lewis' request on the risk of OI or EDS VII in a carrier of 46 XY inv(7)q21-q22 , I can offer the following comments: 1. It is correct that COL1A2 maps in that area. 2. If the gene were interrupted by the inversion, you might expect a mild or even asymptomatic form of OI, as truncated chains would most probably NOT participate in collagen trimer formation ( = null allele of COL1A2 has no or minimal clinical consequences). 3. If I remember well (but I have no time to check the paper - was it a Alex Knisely case?), the reported case of severe OI with such an inversion had to be explained as "that inversion PLUS a structural mutation on the other chromosome". I would check for that. 4. EDS type VIIB is equally highly unlikely. That is caused by exon 6 skipping mutations only, not likely to be produced by a break through the gene. 5. IF the COL1A2 gene were indeed interrupted by the inversion, the proband would have to rely on an intact gene on the other chromosome. A mutation in the other gene might indeed be deleterious. 6. I would not worry with OI - especially if good ultrasound (at what gestational week?) is normal. 7. Perhaps one should worry about other consequences - often, inversions which appear to be balanced do have clinical consequences - mental retardation or so. Check the parents, it would be very nice to find the same in one parent. Good luck and best regards. Please do let us know the outcome. PD Dr. A. Superti-Furga Division of Metabolic and Molecular Diseases Department of Pediatrics University of Zurich CH-8032 Zurich, Switzerland Phone +41-1-266-7722 FAX +41-1-266-7167 Email asuperti@kispi.unizh.ch ************************************************************** We are interested in information about groups that study Lipodystrophy and molecular aspects of Osteogenesis Imperfecta types II and III.You can write direct to the email vferraz@usp.br or to HUM-MOLGEN list. Thanks. ******************************************************************* ########## Victor E. de Faria Ferraz || Dep. Genetica-FMRP-USP ########## ### Email: vferraz@usp.br || Rib. Preto-SP-Brasil ### ********************************************************* I am in my last year of undergraduate study and am currently working at the neurogenetics lab at the Kennedy Krieger Institute of Johns Hopkins University. I am performing biochemical genetic research on certain metabolic diseases and would like to find some information on one which affects my family. My family has what is known as familial myoclonus, but it is unlike any other strain of the disease. Baltic myoclonus and epileptic myoclonus have been ruled out. It is an autosomal dominant disease which was passed on by my father and exists in 2 of the 4 children in my family, my younger brother and sister. We have hit a dead end though, there is no more information which can be given to us by the doctors we have seen. Could anyone doing research or with any knowledge of the disorder please send me some information or a place where I could find it. The disease only seems to affect the motor cortex functions and causes sudden jerks. It however does not cause seizures or any mental abnormalities. My e-mail address is Hlubbs@erols.com, please direct any comments to Chris. My sincere thanks, Apparent patient location: Maryland, US PLEASE REPLY DIRECTLY TO HUMAN MOLECULAR GENETICS NETWORK ************************************************************** I am interested in persuing the use of the adeno-associated virus as a vector to introduce the normal FMR-1 gene into the brains of the Fragile X "knockout mouse" model. I am a family physician with a full time medical practice in Toronto,Ontario, Canada. In July of 1995 my wife and I learned that two of our three young sons had inherited the Fragile X syndrome. They were 3 years old and 18 months old respectively. I was very surprised to learn how little the general medical profession knew about the condition , and even more distressed when I learned how low a research priority it was in the academic community. I wanted to use my scientific and medical background to take things into my own hands, so that a treatment could be found in time to benefit my own children. Consequently, I began reading every scientific paper written on the subject. I believe that the tremendous advances that have occurred in molecular genetics over the past five years have set the stage for animal trials and ultimately some form of gene therapy for the Fragile X syndrome in humans in the next 5 to 10 years. My delemma is that I have been trained as a clinician and have no research experience and no formal university affiliation. I understand the theory involved but know nothing of the practical aspects, such as the equipment and materials required for molecular modeling, recombinant DNA cloning, sequencing and expression etc. This is only my second step of the proverbial "thousand mile journey", and I need this information when I approach the various labs in the area to negotiate the use of their equipment for this research. Thank you once again for your kind attention and cooperation in this matter. I hope you find this information helpful in defining my position and goals, and look forward to hearing from you in the near future. Carlo Paribello M.D. Toronto, Ont. Canada paribel@IBM.NET ************************************************************** With regard to the 12,4 translocation patient, we have some experience with chr12 abnormalities. I would be happy to provide info to thi s patient, but would need more information regarding the details of the cytogenetic localization of the breakpoints, i.e. what giemsa band. Craig T. Basson M.D, Ph.D. Cardiovascular Genetics Center Brigham and Women's Hospital Boston, MA Pager (617)732-6987, #4133 Email Basson@rascal.med.harvard.edu ************************************************************** Hi, My name is Markus Stumm, I am a biologist and I am the leader of the cytogenetic lab in the institute of human genetics Magdeburg. Our institute is part of the university hospital Magdeburg. In our lab we are performing prenatal and postnatal routine diagnosis. We are offering special diagnostic for AT, AT-V, ICFS and for patients who react hypersensitiv to irradiation (e. g. X-ray, gamma-ray). My main topics in science are chromosomal instability syndromes and radiosensitivity. I have performed cell fusion studies in ICFS (Schuffenhauer et al., Human Genet. 1995) and AT-V (NBS)(submitted). Also, I have performed linkage analysis of AT-V patients (Stumm et al., AJHG 1995). For further cell fusion studies (testing for heterogeneity) and linkage analysis (are soon in progress for AT-V) it it is necessary to collect more patients suffering from these rare diseases. Only an optimal number of exactly diagnosed patients, can lead to the isolation of genes responsible for these diseases. I have good connections to other labs working in this field (e.g. the german AT-consortium). Therefore, I you have any patients with clinical hallmarks of AT, AT-V or ICF please contact me for cytogenetic diagnosis. Furthermore, if you have radiosensitive tumor-patients please contact me to create a project. ************************************************************** **************************************************************