ABSTRACT
Neurofibromatosis-Noonan syndrome (NFNS) is a clinical entity possessing traits of autosomal dominant disorders neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). Germline mutations that disrupt the RAS/MAPK pathway are involved in the pathogenesis of both NS and NF1. In light of a studied Greek family, a new theory for etiological pathogenesis of NFNS is suggested. The NFNS phenotype may be the final result of a combination of a genetic factor (a mutation in the NF1 gene) and an environmental factor with the epigenetic effects of muscle hypotonia (such as hydantoin in the reported Greek family), causing hypoplasia of the face and micrognathia.
Subject(s)
Epigenomics , Germ-Line Mutation , Neurofibromatoses/genetics , Noonan Syndrome/genetics , DNA Mutational Analysis , Family Health , Female , Genetic Predisposition to Disease/genetics , Humans , MAP Kinase Signaling System/genetics , Male , Mutation , Neurofibromin 1/genetics , Pedigree , Syndrome , ras Proteins/geneticsABSTRACT
BACKGROUND: Thrombophilia-related mutations, such as coagulation factor V Leiden and factor II (G20210A), have been associated with female infertility due to spontaneous abortions during pregnancy. The possible role of mutations of these two factors in male infertility has not been studied to date. MATERIALS AND METHODS: A total of 208 unrelated Greek men were investigated, including 108 infertile men with idiopathic oligozoospermia, azoospermia, and oligozoospermia of various etiologies, as well as 100 fertile male controls. DNA extracted from participants' sperm or blood was analyzed for factor V Leiden and factor II G20210A mutations. RESULTS: There were no significant differences in factor V and factor II genotypes between infertile men and normal controls. CONCLUSION: An association of the two common thrombophilia-related mutations with male infertility was not observed in this preliminary study.
Subject(s)
Factor V/genetics , Infertility, Male/genetics , Mutation , Prothrombin/genetics , Alleles , Azoospermia/blood , Azoospermia/genetics , Gene Frequency , Genotype , Greece , Humans , Infertility, Male/blood , Male , Oligospermia/blood , Oligospermia/geneticsABSTRACT
BACKGROUND/AIM: Neurofibromatosis 1-Noonan syndrome (NFNS) presents combined characteristics of both autosomal dominant disorders: NF1 and Noonan syndrome (NS). The genes causing NF1 and NS are located on different chromosomes, making it uncertain whether NFNS is a separate entity as previously suggested, or rather a clinical variation. PATIENTS AND METHODS: We present a four-membered Greek family. The father was diagnosed with familial NF1 and the mother with generalized epilepsy, being under hydantoin treatment since the age of 18 years. Their two male children exhibited NFNS characteristics. RESULTS: The father and his sons shared R1947X mutation in the NF1 gene. The two children with NFNS phenotype presented with NF1 signs inherited from their father and fetal hydantoin syndrome-like phenotype due to exposure to that anticonvulsant during fetal development. CONCLUSION: The NFNS phenotype may be the result of both a genetic factor (mutation in the NF1 gene) and an epigenetic/environmental factor (e.g. hydantoin).
