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Male-to-male Transmission (male-to-male + transmission)
Selected AbstractsOropharyngeal Skeletal Disease Accompanying High Bone Mass and Novel LRP5 Mutation,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005Michael R Rickels Abstract Gain-of-function mutation in the gene encoding LRP5 causes high bone mass. A 59-year-old woman carrying a novel LRP5 missense mutation, Arg154Met, manifested skeletal disease affecting her oropharynx as well as dense bones, showing that exuberant LRP5 effects are not always benign. Introduction: Gain-of-function mutation (Gly171Val) of LDL receptor-related protein 5 (LRP5) was discovered in 2002 in two American kindreds with high bone mass and benign phenotypes. In 2003, however, skeletal disease was reported for individuals from the Americas and Europe carrying any of six novel LRP5 missense mutations affecting the same LRP5 protein domain. Furthermore, in 2004, we described a patient with neurologic complications from dense bones and extensive oropharyngeal exostoses caused by the Gly171Val defect. Materials and Methods: A 59-year-old woman was referred for dense bones. Three years before, mandibular buccal and lingual exostoses (osseous "tori") were removed because of infections from food trapping between the teeth and exostoses. Maxillary buccal and palatal exostoses were asymptomatic. Radiographic skeletal survey showed marked thickening of the skull base and diaphyses of long bones (endosteal hyperostosis). BMD Z scores assessed by DXA were +8.5 and +8.7 in the total hip and L1 -L4 spine (both ,195% average control), respectively. LRP5 mutation analysis was carried out for the LRP5 domain known to cause high bone mass. Results: Biochemical evaluation excluded most secondary causes of dense bones, and male-to-male transmission in her family indicated autosomal dominant inheritance. PCR amplification and sequencing of LRP5 exons 2-4 and adjacent splice sites revealed heterozygosity for a new LRP5 missense mutation, Arg154Met. Conclusions: LRP5 Arg154Met is a novel defect that changes the same first ",-propeller" module as the eight previously reported LRP5 gain-of-function missense mutations. Arg154Met alters a region important for LRP5 antagonism by dickkopf (Dkk). Therefore, our patient's extensive oropharyngeal exostoses and endosteal hyperostosis likely reflect increased Wnt signaling and show that exuberant LRP5 effects are not always benign. [source] Mutational analysis of GJB1, MPZ, PMP22, EGR2, and LITAF/SIMPLE in Serbian Charcot-Marie-Tooth patientsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2009Milica Keckarevic-Markovic Abstract We report the results of mutational analysis in the following genes: GJB1, MPZ, PMP22, EGR2, and LITAF/SIMPLE in 57 Charcot-Marie-Tooth (CMT) patients of Serbian origin without the PMP22 duplication. We found 10 different mutations in 14 CMT patients: 6 mutations in GJB1, 3 in MPZ, and 1 in PMP22. Five of six GJB1 mutations are reported for the first time, and the most frequent one appears to be a founder mutation in the Serbian population. No mutations were found in EGR2 or LITAF. Thus, GJB1 mutation analysis should be done in patients without the PMP22 duplication and male-to-male transmission of CMT. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 76JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003D Pareyson The X-linked form of Charcot-Marie-Tooth disease (CMTX) is associated with mutations in the Connexin 32 gene (Cx32) and is the second most common CMT subtype after CMT1A, in which the 17p11.2 duplication is the underlying molecular defect. CMTX is characterized by no male-to-male transmission, intermediate motor conduction velocities (MCV), and more severe disease in males. In our series of CMT patients, we found 9 different Cx32 mutations in 11 families. Overall there were 26 patients, 13 males and 13 females, aged 11,76 yrs. Age at onset ranged considerably (1,60 yrs), but symptoms began earlier in males (mean 15.4 yrs, 77% within age 20) than in females (mean 25 yrs). All patients were autonomous, but disease severity was greater in males, while 4 female carriers were asymptomatic. Pain and tremor were frequent complaints. Two patients had Babinski sign and one had rest tremor. Nerve conduction studies were performed in 23 patients (13 males, 10 females). Upper limb motor conduction velocities (MCV) ranged between 25 and 57 m/s, and were slower in males (25,48 m/s) than in females (34,57 m/s). MCV were in the upper range of CMT1 (25,38 m/s) in 10/13 males but only in 3/10 females. In some cases, nerve conduction slowing was non-uniform within single nerves, and one female patient had a previous diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy. There was considerable asymmetry of involvement between different nerves. The median nerve was often more severely affected than the ulnar nerve, and not only in females, as previously reported, but also in males. Therefore, it appears unlikely that this asymmetry is accounted for by a Lyonization phenomenon. Subclinical abnormalities of central nervous system as revealed by multimodal evoked potential studies were found in 8/10 patients. Expression of Cx32 in the brain is the likely explanation of this finding that confirms previous non-systematic observations. We found seven missense and two nonsense mutations (one novel mutation). Two families presented distinct mutations at the same codon (Arg164), while the Arg22Stop and Arg220Stop mutations were each found in two unrelated cases. Partially supported by a grant from the Italian Ministry of Health to F.T and D.P. (Progetto Ricerca Finalizzata ICS 030.3/RF00.174). [source] Phenotypic characterization of DYT13 primary torsion dystonia,MOVEMENT DISORDERS, Issue 2 2004Anna Rita Bentivoglio MD Abstract We describe the phenotype of DYT13 primary torsion dystonia (PTD) in a family first examined in 1994. A complete neurological evaluation was performed on all available family members: 8 individuals were definitely affected by dystonia. The family was re-evaluated in March 2000: at that time, 3 more individuals had developed symptoms of dystonia. Inheritance of PTD was autosomal dominant, with affected individuals spanning three consecutive generations and male-to-male transmission. Age at onset ranged from 5 to 43 years. Onset occurred either in the craniocervical region or in upper limbs. Progression was mild, and the disease course was benign in most affected individuals; generalization occurred only in 2 cases. We did not find anticipation of age at onset or of disease severity through generations. Most subjects presented with jerky, myoclonic-like dystonic movements of the neck or shoulders. DYT13-PTD is an autosomal dominant disease, with incomplete penetrance (58%). Clinical presentation and age at onset were more variable than in DYT1-PTD, and the neck was involved in most of those affected. Moreover, the individuals with generalised dystonia were not severely disabled and were able to lead independent lives. To date, this is the only family with DYT13-PTD. © 2003 Movement Disorder Society [source] | ||||||||||