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Papers by savina dipresa

Research paper thumbnail of Molecular Bases of Sperm Thermotaxis: Old and New Knowledges

Protein & Peptide Letters, 2018

Research paper thumbnail of New Markers for Predicting Fertility of the Male Gametes in the Post Genomic Era

Protein & Peptide Letters, 2018

Research paper thumbnail of Sperm Count and Hypogonadism as Markers of General Male Health

European Urology Focus, 2019

Background: Some evidence suggests that infertile men, who are at increased risk for hypogonadism... more Background: Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive. Objective: We tested whether semen quality and reproductive function could represent a marker of general male health. Design, setting, and participants: A retrospective study of 5177 individuals from a prospectively collected database of 11 516 males of infertile couples who had semen analysis in a tertiary university center. Outcome measurements and statistical analysis: Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone <10.5 nmol/l and/or luteinizing hormone >9.4 IU/l. Individuals with a total sperm count of <10 million had genetic testing (karyotype, Y chromosome microdeletions, and CFTR gene mutations) and those with hypogonadism underwent dual-energy x-ray absorptiometry for bone mineral density. Descriptive statistics and odds ratio (OR) calculation were used. Results and limitations: Men with a low sperm count (<39 million/ejaculate) are at a high risk of hypogonadism (OR 12.2, 95% confidence interval [CI] 10.2-14.6) and have higher body mass index, waist circumference, systolic pressure, low-density lipoprotein cholesterol, triglycerides, and homeostatic model assessment (HOMA) index; lower high-density lipoprotein cholesterol; and a higher prevalence of metabolic syndrome (OR 1.246, 95 CI 1.005-1.545). All data are worse in men with hypogonadism, but a low sperm count per se is associated with a poor metabolic parameter. Men with hypogonadism have lower bone mineral density and 51% prevalence of osteoporosis/osteopenia. Longitudinal studies are necessary to support these data. Conclusions: This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health.

Research paper thumbnail of Epigenetica e spermatogenesi

L'Endocrinologo, 2019

SommarioAl momento della fecondazione il corredo genetico spermatico non è costituito esclusivame... more SommarioAl momento della fecondazione il corredo genetico spermatico non è costituito esclusivamente dalla sequenza aploide del DNA, ma comprende anche complesse informazioni epigenetiche capaci di influenzare l’espressione genica, con ripercussioni sulla funzionalità degli stessi gameti, sullo sviluppo embrionale e diversi aspetti della vita postnatale. Numerosi fattori ambientali possono indurre cambiamenti dell’epigenoma spermatico che, oltre a influenzare la capacità fertile dell’individuo, possono essere trasmessi transgenerazionalmente avendo un profondo impatto sullo sviluppo della prole.

Research paper thumbnail of Contemporary genetics-based diagnostics of male infertility

Expert Review of Molecular Diagnostics, 2019

Introduction Thousands of genes are implicated in spermatogenesis, testicular development and end... more Introduction Thousands of genes are implicated in spermatogenesis, testicular development and endocrine regulation of testicular function. The genetic contribution to male infertility is therefore considerable, and basic and clinical research in last years found a number of genes that could potentially be used in clinical practice. Research has also been pushed by new technologies for genetic analysis. However, genetic analyses currently recommended in standard clinical practice are still relatively few. Areas covered We review the genetic causes of male infertility, distinguishing those already approved for routine clinical application from those that are still not supported by adequate clinical studies or those responsible for very rare cause of male infertility. Genetic causes of male infertility vary from chromosomal abnormalities to copy number variations (CNVs), to single-gene mutations. Expert opinion Clinically, the most important aspect is related to the correct identification of subjects to be tested and the right application of genetic tests based on clear clinical data. A correct application of available genetic tests in the different forms of male infertility allows receiving a better and defined diagnosis, has important role in clinical decision (treatment, prognosis), and allows appropriate genetic counselling especially in cases that should undergo assisted reproduction techniques.

Research paper thumbnail of Is there any clinical relevant difference between non mosaic Klinefelter Syndrome patients with or without Androgen Receptor variations?

Research paper thumbnail of Next generation sequencing in nonsyndromic intellectual disability: From a negative molecular karyotype to a possible causative mutation detection

American Journal of Medical Genetics Part A, 2013

The identification of causes underlying intellectual disability (ID) is one of the most demanding... more The identification of causes underlying intellectual disability (ID) is one of the most demanding challenges for clinical Geneticists and Researchers. Despite molecular diagnostics improvements, the vast majority of patients still remain without genetic diagnosis. Here, we report the results obtained using Whole Exome and Target Sequencing on nine patients affected by isolated ID without pathological copy number variations, which were accurately selected from an initial cohort of 236 patients. Three patterns of inheritance were used to search for: (1) de novo, (2) X-linked, and (3) autosomal recessive variants. In three of the nine proband-parent trios analyzed, we identified and validated two de novo and one X-linked potentially causative mutations located in three ID-related genes. We proposed three genes as ID candidate, carrying one de novo and three X-linked mutations. Overall, this systematic proband-parent trio approach using next generation sequencing could explain a consistent percentage of patients with isolated ID, thus increasing our knowledge on the molecular bases of this disease and opening new perspectives for a better diagnosis, counseling, and treatment.

Research paper thumbnail of Refining the mutational spectrum and gene–phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study

Journal of Medical Genetics

BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorde... more BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.MethodsWe performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.ResultsA genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which account...

Research paper thumbnail of Lactase non-persistent genotype distribution in Italy

Minerva gastroenterologica e dietologica, 2017

BACKGROUND Adult-type hypolactasia is a frequent condition of lactose malabsorption; in Europe th... more BACKGROUND Adult-type hypolactasia is a frequent condition of lactose malabsorption; in Europe the distribution of adult-type hypolactasia have been shown to display a North-South gradient. Genotyping for LCT-13910 C>T polymorphism has been proposed as a useful diagnostic marker of adult-type hypolactasia. Data concerning lactase non-persistent genotype distribution in Italy are confused and not well characterized. The aim of this study was to determine the prevalence of CC-genotype corresponding to lactase non-persistence in Italian population. METHODS We genotyped 1312 adult Italian subjects for LCT-13910 C>T polymorphism by KASPar chemistry (KBioscience Ltd., Hoddesdon, England, UK). RESULTS The frequency of the lactase non-persistence genotype of our sample was 62.3% that was higher than the values published for adult hypolactasia in Italy. In our study a frequency of 58.6%, 74.1% and 67.1% was detected in the three main macro-regions of Italy (North, Center, and South), r...

Research paper thumbnail of Causes of Extra Chromosome(s)

Under normal conditions, men have 46 chromosomes, including 44 numbered chromosomes (two copies o... more Under normal conditions, men have 46 chromosomes, including 44 numbered chromosomes (two copies of each chromosome numbered 1 to 22) and two sex chromosomes, one X and one Y. Men with Klinefelter syndrome have an arrangement with an extra sex chromosome: 47,XXY instead of the usual 46,XY (Bock, Understanding Klinefelter syndrome: a guide for XXY males and their families, su NIH Pub. No. 93–3202, Office of Research Reporting, NICHD, agosto 1993).

Research paper thumbnail of Genetics of hearing loss (from congenital forms to presbycusis)

Research paper thumbnail of Refining the mutational spectrum and gene–phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study

Journal of Medical Genetics

BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorde... more BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.MethodsWe performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.ResultsA genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which account...

Research paper thumbnail of Genetic testing in male infertility

Infertility is a major health problem which affects approximately 22% of married couples in repro... more Infertility is a major health problem which affects approximately 22% of married couples in reproductive age. The apparent increased incidence of male infertility, in parallel with the widespread use of in vitro fertilization (IVF), raises concern as to the impact of advanced assisted conception techniques in transmitting genetic anomalies to the offspring. Recent research has widely focused on genetic factors underlying male infertility and several genetic tests are now clinically available. Genetic testing plays an important role not only to identify the etiology of male infertility but also aids in counseling as well as in the prevention of the transmission of genetic defects to the offspring via assisted reproduction. This review is focused on the syndromic and non-syndromic causes of male infertility and the diagnostic tests use in their evaluation.

Research paper thumbnail of A new case of TAR syndrome confirms the importance of noncoding variants in the etiopathogenesis of the disease

Research paper thumbnail of Molecular Bases of Sperm Thermotaxis: Old and New Knowledges

Protein & Peptide Letters, 2018

Research paper thumbnail of New Markers for Predicting Fertility of the Male Gametes in the Post Genomic Era

Protein & Peptide Letters, 2018

Research paper thumbnail of Sperm Count and Hypogonadism as Markers of General Male Health

European Urology Focus, 2019

Background: Some evidence suggests that infertile men, who are at increased risk for hypogonadism... more Background: Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive. Objective: We tested whether semen quality and reproductive function could represent a marker of general male health. Design, setting, and participants: A retrospective study of 5177 individuals from a prospectively collected database of 11 516 males of infertile couples who had semen analysis in a tertiary university center. Outcome measurements and statistical analysis: Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone <10.5 nmol/l and/or luteinizing hormone >9.4 IU/l. Individuals with a total sperm count of <10 million had genetic testing (karyotype, Y chromosome microdeletions, and CFTR gene mutations) and those with hypogonadism underwent dual-energy x-ray absorptiometry for bone mineral density. Descriptive statistics and odds ratio (OR) calculation were used. Results and limitations: Men with a low sperm count (<39 million/ejaculate) are at a high risk of hypogonadism (OR 12.2, 95% confidence interval [CI] 10.2-14.6) and have higher body mass index, waist circumference, systolic pressure, low-density lipoprotein cholesterol, triglycerides, and homeostatic model assessment (HOMA) index; lower high-density lipoprotein cholesterol; and a higher prevalence of metabolic syndrome (OR 1.246, 95 CI 1.005-1.545). All data are worse in men with hypogonadism, but a low sperm count per se is associated with a poor metabolic parameter. Men with hypogonadism have lower bone mineral density and 51% prevalence of osteoporosis/osteopenia. Longitudinal studies are necessary to support these data. Conclusions: This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health.

Research paper thumbnail of Epigenetica e spermatogenesi

L'Endocrinologo, 2019

SommarioAl momento della fecondazione il corredo genetico spermatico non è costituito esclusivame... more SommarioAl momento della fecondazione il corredo genetico spermatico non è costituito esclusivamente dalla sequenza aploide del DNA, ma comprende anche complesse informazioni epigenetiche capaci di influenzare l’espressione genica, con ripercussioni sulla funzionalità degli stessi gameti, sullo sviluppo embrionale e diversi aspetti della vita postnatale. Numerosi fattori ambientali possono indurre cambiamenti dell’epigenoma spermatico che, oltre a influenzare la capacità fertile dell’individuo, possono essere trasmessi transgenerazionalmente avendo un profondo impatto sullo sviluppo della prole.

Research paper thumbnail of Contemporary genetics-based diagnostics of male infertility

Expert Review of Molecular Diagnostics, 2019

Introduction Thousands of genes are implicated in spermatogenesis, testicular development and end... more Introduction Thousands of genes are implicated in spermatogenesis, testicular development and endocrine regulation of testicular function. The genetic contribution to male infertility is therefore considerable, and basic and clinical research in last years found a number of genes that could potentially be used in clinical practice. Research has also been pushed by new technologies for genetic analysis. However, genetic analyses currently recommended in standard clinical practice are still relatively few. Areas covered We review the genetic causes of male infertility, distinguishing those already approved for routine clinical application from those that are still not supported by adequate clinical studies or those responsible for very rare cause of male infertility. Genetic causes of male infertility vary from chromosomal abnormalities to copy number variations (CNVs), to single-gene mutations. Expert opinion Clinically, the most important aspect is related to the correct identification of subjects to be tested and the right application of genetic tests based on clear clinical data. A correct application of available genetic tests in the different forms of male infertility allows receiving a better and defined diagnosis, has important role in clinical decision (treatment, prognosis), and allows appropriate genetic counselling especially in cases that should undergo assisted reproduction techniques.

Research paper thumbnail of Is there any clinical relevant difference between non mosaic Klinefelter Syndrome patients with or without Androgen Receptor variations?

Research paper thumbnail of Next generation sequencing in nonsyndromic intellectual disability: From a negative molecular karyotype to a possible causative mutation detection

American Journal of Medical Genetics Part A, 2013

The identification of causes underlying intellectual disability (ID) is one of the most demanding... more The identification of causes underlying intellectual disability (ID) is one of the most demanding challenges for clinical Geneticists and Researchers. Despite molecular diagnostics improvements, the vast majority of patients still remain without genetic diagnosis. Here, we report the results obtained using Whole Exome and Target Sequencing on nine patients affected by isolated ID without pathological copy number variations, which were accurately selected from an initial cohort of 236 patients. Three patterns of inheritance were used to search for: (1) de novo, (2) X-linked, and (3) autosomal recessive variants. In three of the nine proband-parent trios analyzed, we identified and validated two de novo and one X-linked potentially causative mutations located in three ID-related genes. We proposed three genes as ID candidate, carrying one de novo and three X-linked mutations. Overall, this systematic proband-parent trio approach using next generation sequencing could explain a consistent percentage of patients with isolated ID, thus increasing our knowledge on the molecular bases of this disease and opening new perspectives for a better diagnosis, counseling, and treatment.

Research paper thumbnail of Refining the mutational spectrum and gene–phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study

Journal of Medical Genetics

BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorde... more BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.MethodsWe performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.ResultsA genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which account...

Research paper thumbnail of Lactase non-persistent genotype distribution in Italy

Minerva gastroenterologica e dietologica, 2017

BACKGROUND Adult-type hypolactasia is a frequent condition of lactose malabsorption; in Europe th... more BACKGROUND Adult-type hypolactasia is a frequent condition of lactose malabsorption; in Europe the distribution of adult-type hypolactasia have been shown to display a North-South gradient. Genotyping for LCT-13910 C>T polymorphism has been proposed as a useful diagnostic marker of adult-type hypolactasia. Data concerning lactase non-persistent genotype distribution in Italy are confused and not well characterized. The aim of this study was to determine the prevalence of CC-genotype corresponding to lactase non-persistence in Italian population. METHODS We genotyped 1312 adult Italian subjects for LCT-13910 C>T polymorphism by KASPar chemistry (KBioscience Ltd., Hoddesdon, England, UK). RESULTS The frequency of the lactase non-persistence genotype of our sample was 62.3% that was higher than the values published for adult hypolactasia in Italy. In our study a frequency of 58.6%, 74.1% and 67.1% was detected in the three main macro-regions of Italy (North, Center, and South), r...

Research paper thumbnail of Causes of Extra Chromosome(s)

Under normal conditions, men have 46 chromosomes, including 44 numbered chromosomes (two copies o... more Under normal conditions, men have 46 chromosomes, including 44 numbered chromosomes (two copies of each chromosome numbered 1 to 22) and two sex chromosomes, one X and one Y. Men with Klinefelter syndrome have an arrangement with an extra sex chromosome: 47,XXY instead of the usual 46,XY (Bock, Understanding Klinefelter syndrome: a guide for XXY males and their families, su NIH Pub. No. 93–3202, Office of Research Reporting, NICHD, agosto 1993).

Research paper thumbnail of Genetics of hearing loss (from congenital forms to presbycusis)

Research paper thumbnail of Refining the mutational spectrum and gene–phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study

Journal of Medical Genetics

BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorde... more BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.MethodsWe performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.ResultsA genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which account...

Research paper thumbnail of Genetic testing in male infertility

Infertility is a major health problem which affects approximately 22% of married couples in repro... more Infertility is a major health problem which affects approximately 22% of married couples in reproductive age. The apparent increased incidence of male infertility, in parallel with the widespread use of in vitro fertilization (IVF), raises concern as to the impact of advanced assisted conception techniques in transmitting genetic anomalies to the offspring. Recent research has widely focused on genetic factors underlying male infertility and several genetic tests are now clinically available. Genetic testing plays an important role not only to identify the etiology of male infertility but also aids in counseling as well as in the prevention of the transmission of genetic defects to the offspring via assisted reproduction. This review is focused on the syndromic and non-syndromic causes of male infertility and the diagnostic tests use in their evaluation.

Research paper thumbnail of A new case of TAR syndrome confirms the importance of noncoding variants in the etiopathogenesis of the disease