Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the avail...Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator （CFTR） gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach： （i） first, a reverse dot-blot analysis was performed to detect mutations with regional impact; （ii） next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and （iii） finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.展开更多
Over the years,accumulating evidence has confirmed the crucial role of cystic fibrosis transmembrane conductance regulator(CFTR)mutations in male infertility caused by congenital bilateral absence of the vas deferens(...Over the years,accumulating evidence has confirmed the crucial role of cystic fibrosis transmembrane conductance regulator(CFTR)mutations in male infertility caused by congenital bilateral absence of the vas deferens(CBAVD),the most common cause of obstructive azoospermia(OA).1,2 The distribution and frequency of CFTR mutations in CBAVD patients vary considerably across countries and ethnic groups,and this suggests the need to develop regional variant panels to significantly improve diagnosis and management of infertile males.展开更多
Williams syndrome (WS) is a genetic disorder caused by a heterozygous contiguous gene deletion on chromosome 7q11.23. Clinical features of the disease include low IQ and deficit in some cog- nitive domains, and the pr...Williams syndrome (WS) is a genetic disorder caused by a heterozygous contiguous gene deletion on chromosome 7q11.23. Clinical features of the disease include low IQ and deficit in some cog- nitive domains, and the presence of relatively strong abilities in social drive, face processing, language, and musical skills. The presence of a strong predisposition to the development of musicality in individuals affected by WS leads us to suppose that some genes deleted in this syndrome are somehow involved in the evolution of this ability, and that these genes could act in normal conditions as “suppressors of music ability”. To test this hypothesis, we carried out an “in silico” analysis by using the Ingenuity Pathway Analysis (IPA) software to identify the interaction between genes mapped in the WS critical region and genes previously related to musical ability by literature data. This approach allowed us to identify 3 networks of interaction, involving AVPR1A, NCF1, UNC5C and LAT2 in the first network, STX1A and SLC6A4 in the second one and only WS related genes in the last one. Among these associations, the one involving STX1A and SLC6A4 suggested a possible mechanism of interaction was based on the influence played by STX1A deletion on the serotonin levels through a decrease of SLC6A4 activity.展开更多
文摘Congenital bilateral absence of vas deferens （CBAVD） is a manifestation of the mildest form of cystic fibrosis （CF） and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator （CFTR） gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach： （i） first, a reverse dot-blot analysis was performed to detect mutations with regional impact; （ii） next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and （iii） finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.
文摘Over the years,accumulating evidence has confirmed the crucial role of cystic fibrosis transmembrane conductance regulator(CFTR)mutations in male infertility caused by congenital bilateral absence of the vas deferens(CBAVD),the most common cause of obstructive azoospermia(OA).1,2 The distribution and frequency of CFTR mutations in CBAVD patients vary considerably across countries and ethnic groups,and this suggests the need to develop regional variant panels to significantly improve diagnosis and management of infertile males.
文摘Williams syndrome (WS) is a genetic disorder caused by a heterozygous contiguous gene deletion on chromosome 7q11.23. Clinical features of the disease include low IQ and deficit in some cog- nitive domains, and the presence of relatively strong abilities in social drive, face processing, language, and musical skills. The presence of a strong predisposition to the development of musicality in individuals affected by WS leads us to suppose that some genes deleted in this syndrome are somehow involved in the evolution of this ability, and that these genes could act in normal conditions as “suppressors of music ability”. To test this hypothesis, we carried out an “in silico” analysis by using the Ingenuity Pathway Analysis (IPA) software to identify the interaction between genes mapped in the WS critical region and genes previously related to musical ability by literature data. This approach allowed us to identify 3 networks of interaction, involving AVPR1A, NCF1, UNC5C and LAT2 in the first network, STX1A and SLC6A4 in the second one and only WS related genes in the last one. Among these associations, the one involving STX1A and SLC6A4 suggested a possible mechanism of interaction was based on the influence played by STX1A deletion on the serotonin levels through a decrease of SLC6A4 activity.
