Expanding the mutational spectrum of monogenic hypogonadotropic hypogonadism: novel mutations in ANOS1 and FGFR1 genes.

BACKGROUND: Congenital hypogonadotropic hypogonadism (CHH) is a rare disease, triggered by defective GnRH secretion, that is usually diagnosed in late adolescence or early adulthood due to the lack of spontaneous pubertal development. To date more than 30 genes have been associated with CHH pathogenesis with X-linked recessive, autosomal dominant, autosomal recessive and oligogenic modes of inheritance. Defective sense of smell is present in about 50-60% of CHH patients and called Kallmann syndrome (KS), in contrast to patients with normal sense of smell referred to as normosmic CHH. ANOS1 and FGFR1 genes are all well established in the pathogenesis of CHH and have been extensively studied in many reported cohorts. Due to rarity and heterogenicity of the condition the mutational spectrum, even in classical CHH genes, have yet to be fully characterized. METHODS: To address this issue we screened for ANOS1 and FGFR1 variants in a cohort of 47 unrelated CHH subjects using targeted panel sequencing. All potentially pathogenic variants have been validated with Sanger sequencing. RESULTS: Sequencing revealed two ANOS1 and four FGFR1 mutations in six subjects, of which five are novel and one had been previously reported in CHH. Novel variants include a single base pair deletion c.313delT in exon 3 of ANOS1, three missense variants of FGFR1 predicted to result in the single amino acid substitutions c.331C > T (p.R111C), c.1964 T > C (p.L655P) and c.2167G > A (p.E723K) and a 15 bp deletion c.374_388delTGCCCGCAGACTCCG in exon 4 of FGFR1. Based on ACMG-AMP criteria reported variants were assigned to class 5, pathogenic or class 4, likely pathogenic. Protein structural predictions, the rarity of novel variants and amino acid conservation in case of missense substitutions all provide strong evidence that these mutations are highly likely to be deleterious. CONCLUSIONS: Despite the fact that ANOS1 and FGFR1 are classical CHH genes and were thoroughly explored in several CHH cohorts we identified new, yet undescribed variants within their sequence. Our results support the genetic complexity of the disorder. The knowledge of the full genetic spectrum of CHH is increasingly important in order to be able to deliver the best personalised medical care to our patients.

Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome.

Hartsfield syndrome is a rare clinical entity characterized by holoprosencephaly and ectrodactyly with the variable feature of cleft lip/palate. In addition to these symptoms patients with Hartsfield syndrome can show developmental delay of variable severity, isolated hypogonadotropic hypogonadism, central diabetes insipidus, vertebral anomalies, eye anomalies, and cardiac malformations. Pathogenic variants in FGFR1 have been described to cause phenotypically different FGFR1-related disorders such as Hartsfield syndrome, hypogonadotropic hypogonadism with or without anosmia, Jackson-Weiss syndrome, osteoglophonic dysplasia, Pfeiffer syndrome, and trigonocephaly Type 1. Here, we report three patients with Hartsfield syndrome from two unrelated families. Exome sequencing revealed two siblings harboring a novel de novo heterozygous synonymous variant c.1029G>A, p.Ala343Ala causing a cryptic splice donor site in exon 8 of FGFR1 likely due to gonadal mosaicism in one parent. The third case was a sporadic patient with a novel de novo heterozygous missense variant c.1868A>G, p.(Asp623Gly).

The level of extracellular superoxide dismutase in the first week of life in very and extremely low birth weight infants and the risk of developing bronchopulmonary dysplasia.

Background Antioxidant enzymes may play a significant role in the development of bronchopulmonary dysplasia (BPD). The aim of the study was to assess the relationship between the level of extracellular superoxide dismutase (SOD3) in the serum at days 1 and 7 of life and the risk of developing BPD. Methods The study comprised 103 neonates born before 32 weeks' gestation with a birth weight of ≤1500 g. Results In the investigated group, the median serum SOD3 level at day 1 of life was 4.01 ng/mL [interquartile range (IQR) 2.59-5.09 ng/mL] and at day 7 of life 3.13 ng/mL (IQR 2.49-4.34 ng/mL). A statistically significant decrease in the serum SOD3 level was found in the first week of life, P < 0.0001. No correlation was found between the serum SOD3 level at day 1 of life and gestational age R = 0.07, P = 0.4543 and birth weight R = 0.10, P = 0.3083. No statistically significant correlation was found between the dynamics of change in the SOD3 level in serum at days 1 and 7 of life and the risk of BPD development for the definition of BPD at day 28 of life, P = 0.8764 nor at 36 weeks' postmenstrual age, P = 0.6598. Conclusion The study revealed a statistically significant decrease in the serum SOD3 level in the first week of life in very and extremely low birth weight infants born before 32 weeks of gestation. In the clinical setting, no relationship was observed between the level of SOD3 in serum and the risk of developing BPD.

Environmental exposure to parabens and sperm chromosome disomy.

Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, food and beverage processing due to their board spectrum of activity, inertness, and low cost. The study population consisted of 156 men under 45 years of age who attended the infertility clinic for diagnostic purposes with normal semen concentration of 15-300 mln/ml. Participants were interviewed and provided a semen sample. The parabens concentrations: ethyl paraben (EP), butyl paraben (BP), methyl paraben (MP), and iso-butyl paraben (iBuP) were analyzed in the urine using a validated gas chromatography ion-tap mass spectrometry method. The positive association was found between urinary level of BP and XY18 disomy (p = 0.045) and PP and disomy of chromosome 13 (p = 0.007). This is the first study to examine these relationships, and replication of our findings is needed before the association between parabens concentration in urine and aneuploidy can be fully defined. These findings may be of concern due to increased parabens use.

Human sperm aneuploidy after exposure to polycyclic aromatic hydrocarbons.

The purpose of this cross-sectional study was to investigate whether environmental exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with sperm aneuploidy. A sample of 181 men who attended an infertility clinic for diagnostic purposes and who had a normal semen concentration of 20-300×106 spermatozoa mL-1 or slight oligozoospermia (semen concentration of 15-20×106 spermatozoa mL-1;

New findings in oligogenic inheritance of congenital hypogonadotropic hypogonadism.

Introduction: Congenital hypogonadotropic hypogonadism results from a dysfunction of the hypothalamic-pituitary-gonadal axis, which is essential for the development and function of the reproductive system. It may be associated with anosmia, referred to as Kallmann syndrome, or a normal sense of smell. Numerous studies have proven that hypogonadotropic hypogonadism is not simply a monogenic Mendelian disease, but that more than one gene may be involved in its pathogenesis in a single patient. The oligogenic complex architecture underlying the disease is still largely unknown. Material and methods: Targeted next-generation sequencing (NGS) was used to screen for DNA variants in a cohort of 47 patients with congenital hypogonadotropic hypogonadism. The NGS panel consists of over 50 well-known and candidate genes, associated with hypogonadotropic state. Results: Here we report the identification of new oligogenic variants in SPRY4/SEMA3A, SRA1/SEMA7A, CHD7/SEMA7A, CCDC141/POLR3B/POLR3B, and PROKR2/SPRY4/NSMF. These genes are known to contribute to the phenotype of hypogonadotropic hypogonadism, yet our results point to potential new "partners" underlying digenic and trigenic patterns. Conclusions: The finding supports the importance of oligogenic inheritance and demonstrates the complexity of genetic architecture in hypogonadotropic hypogonadism. It also underlines the necessity for developing fine-tuned guidelines to provide a tool for adequate and precise sequence variant classification in non-Mendelian conditions.

Association between idiopathic recurrent pregnancy loss and genetic polymorphisms in cytokine and matrix metalloproteinase genes.

OBJECTIVES: Recurrent reproductive loss (RPL) is a global health issue affecting a significant number of women. Approximately half of miscarriages have an unexplained etiology. Familial aggregation and twins studies prove that some cases of the RPL could have a genetic background. Recent evidences suggest that cytokines (e.g. IL-6, TNF alpha or TGF beta) and matrix metalloproteinases (MMP) are important for maintenance of pregnancy. Single gene polymorphisms (SNP), affecting these proteins production or their function may predispose to the loss of the pregnancy. The aim of this study was to evaluate the association between the following polymorphisms of IL6 (rs1800795), TNF (rs1800629), TGFB1 (rs1800471), MMP1 (rs1799750), MMP2 (rs2285053 and rs243865), MMP3 (rs35068180), MMP9 (rs3918242) and the recurrent pregnancy loss in polish population. MATERIAL AND METHODS: Study subjects comprised of 67 patients with a history of recurrent pregnancy loss (≥ 2 miscarriages in history) and 75 controls. The distribution of genotypes for selected polymorphisms were determined by RFLP-PCR. RESULTS: Maternal genotypes GG TNF, or 5A/5A MMP3 may be associated with the recurrent pregnancy loss. No association between the IL6, TGFB1, MMP1, MMP2, or MMP9 studied polymorphisms and the predisposition to miscarriage was found. CONCLUSIONS: This study demonstrated a possible association between rs1800629 TNF, rs35068180 MMP3 polymorphisms and recurrent pregnancy loss.

Novel Mutations Within Collagen Alpha1(I) and Alpha2(I) Ligand-Binding Sites, Broadening the Spectrum of Osteogenesis Imperfecta - Current Insights Into Collagen Type I Lethal Regions.

Osteogenesis imperfecta (OI) is a rare genetic disorder demonstrating considerable phenotypic and genetic heterogeneity. The extensively studied genotype-phenotype correlation is a crucial issue for a reliable counseling, as the disease is recognized at increasingly earlier stages of life, including prenatal period. Based on population studies, clusters in COL1A1 and COL1A2 genes associated with the presence of glycine substitutions leading to fatal outcome have been distinguished and named as "lethal regions." Their localization corresponds to the ligand-binding sites responsible for extracellular interactions of collagen molecules, which could explain high mortality associated with mutations mapping to these regions. Although a number of non-lethal cases have been identified from the variants located in lethal clusters, the mortality rate of mutations has not been updated. An next generation sequencing analysis, using a custom gene panel of known and candidate OI genes, was performed on a group of 166 OI patients and revealed seven individuals with a causative mutations located in the lethal regions. Patients' age, ranging between 3 and 25 years, excluded the expected fatal outcome. The identification of non-lethal cases caused by mutations located in lethal domains prompted us to determine the actual mortality caused by glycine substitutions mapping to lethal clusters and evaluate the distribution of all lethal glycine mutations across collagen type I genes, based on records deposited in the OI Variant Database. Finally, we identified six glycine substitutions located in lethal regions of COL1A1 and COL1A2 genes, of which four are novel. The review of all mutations in the dedicated OI database, revealed 33 distinct glycine substitutions in two lethal domains of COL1A1, 26 of which have been associated with a fatal outcome. Similarly, 109 glycine substitutions have been identified in eight lethal clusters of COL1A2, of which 51 have been associated with a fatal manifestation. An analysis of all glycine substitutions leading to fatal phenotype, showed that their distribution along collagen type I genes is not regular, with 17% (26 out of 154) of mutations reported in COL1A1 and 64% (51 out of 80) in COL1A2 corresponding to localization of the lethal regions.

Severe neonatal spondylometaphyseal dysplasia in two siblings.

We report on two siblings with a severe neonatal form of spondylometaphyseal dysplasia (SMD). Similar cases have been reported in four publications. Analysis of pedigree data from the original and present families suggests an autosomal recessive mode of inheritance, although parental gonadal mosaicism is also possible. The similarities in the phenotype between our patients and spondyloepimetaphyseal dysplasia congenita (SEMDC) and spondyloepimetaphyseal dysplasia Strudwick (SEMDS) type, indicated that these patients could have a defect in the COL2A1 gene. Molecular analysis of genomic DNA of these patients excluded this gene. Another potential candidate gene PTHR1, was also analyzed in the selected regions and no mutation was found. This gene is probably causative in the Jansen type of SMD, which shares some phenotypic features with the siblings whom we documented. Our results indicate that a new candidate gene for the reported form of SMD should be sought.

Genetic counseling in Robertsonian translocations der(13;14): frequencies of reproductive outcomes and infertility in 101 pedigrees.

Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. However, most studies aimed at determining risk figures are more than 20 years old. Their results are often contradictory regarding important topics in genetic counseling such as infertility and unfavorable pregnancy outcomes. Here, we present a study on a sample of 101 previously unreported pedigrees of der(13;14)(q10;q10). In order to minimize problems of partial ascertainment, we included families with a wide range of reasons of ascertainment such as birth of a child with congenital anomalies, prenatal diagnosis due to maternal age, fertility problems and recurrent pregnancy loss. No evidence of increased infertility rates of female and male carriers was found. The detected miscarriage frequency of female carriers was higher than previously reported (27.6 +/- 4.0% of all spontaneous pregnancies). This may be explained by an over-correction of earlier studies, which excluded all unkaryotyped miscarriages. In three out of 42 amniocenteses, translocation trisomies 13 were diagnosed (7.1 +/- 4.0% of all amniocenteses). The frequency of stillbirths was 3.3 +/- 1.6% for female carriers and 1.4 +/- 1.4% for male carriers. A low risk for the live birth of translocation trisomy 13 children was confirmed since no live born children with trisomy 13 or Pätau syndrome were detected in the ascertainment-corrected sample.

Regulatory influence of melatonin on collagen accumulation in the infarcted heart scar.

The regulatory influence of the pineal gland on superficial wound healing and collagen content is documented. The aim of the present study was to determine whether the pineal gland and its secretory product melatonin regulate collagen accumulation in the scar of the infarcted heart and to explain the mechanisms of its action. To induce myocardial infarction in rats the left coronary artery was ligated. Metoprolol at the dose of 0.2 mg/100 g body weight (b.w.) was injected intraperitoneally to inhibit melatonin secretion. Pinealectomy was performed on some animals. For the in vitro study, cells were isolated from the heart scar and cultured in Dulbecco's modified Eagle medium with 3% fetal calf serum and antibiotics. Collagen content was evaluated as hydroxyproline content according to the Woessner method. Melatonin subcutaneously injected into the rats at the doses of 30 microg/100 g or 60 microg/100 g b.w. increased collagen accumulation in the heart scar. The doses of 3 microg/100 g b.w. and 300 microg/100 g b.w. were not effective. Surgical and pharmacological pinealectomies had opposite effects and reduced collagen content in the scar. However, melatonin administration (60 microg/100 g b.w.) to pinealectomized rats reversed the effect of pinealectomy and normalized collagen levels in heart after infarction. Cells isolated from the heart scar were identified as myofibroblasts. Melatonin (10(-7)-10(-8) m) increased collagen accumulation in the cultures. Collagen accumulation in the scar of the infarcted heart is regulated by melatonin and it exerts effects directly on the myofibroblasts of the infarcted area. Therefore, melatonin-induced collagen accumulation in the infarcted heart could be considered as the event improving the tensile strength of the scar and retarding the development of complications.

[Diaphragmatic hernia in reference hospital ICZMP--diagnostic problems and outcome]. / Problemy diagnostyczne i losy plodów z przepuklina przeponowa w osrodku referencyjnym ICZMP w latach 1994-2006.

OBJECTIVES: The aim of the study was to analyze US/ECHO examinations in fetuses with diaphragmatic hernia (DH) diagnosed and treated in our institution from 1994-2006, and their follow-up. MATERIAL AND METHODS: Retrospective analysis of the data base from Department for Diagnoses & Prevention of Fetal Malformations, Research Institute of the Polish Mother's Memorial Hospital: 14,481 fetal echo/ultrasound examinations in 10,077 fetuses have been analyzed to retrieve 115 fetuses with DH. RESULTS: The mean gestational age at the targeted US/ECHO examination was 30 wks. There were 8 terminations of pregnancies (at mean 21 wks), 6 intrauterine demises, 60 neonatal deaths after delivery (in 1-3rd day of postnatal life), 8 deaths after surgery, 19 neonates were discharged home and in 14 cases the follow-up could not be monitored. The most common anomalies accompanying DH have been central nervous system anomalies (20%), polyhydramnion (16%) and cong heart defects (10%). In this subgroup, there was 100% mortality. Isolated DH has been diagnosed in every third case. In this subgroup, 27 neonates had undergone surgery and the survival rate was 70%, however since 2004 there was not a single death on record. CONCLUSIONS: Late gestational age of US/ECHO examinations in our tertiary center suggests that DH has been relatively difficult to detect during ultrasound screening. DH and the other structural malformations have been a lethal disease in our series in 100%. Isolated DH was much less frequent and was present in every third case (29%), and in this group the survival rate was 70%, regardless of the way of the delivery (CS or Vaginal).

Air Pollution and Human Sperm Sex Ratio.

The present study was designed to address the hypothesis that exposure to specific air pollutants may impact human sperm Y:X chromosome ratio. The study population consisted of 195 men who were attending an infertility clinic for diagnostic purposes and who had normal semen concentration of 15-300 mln/ml (WHO, 2010). Participants represented a subset of men in a multicenter parent study conducted in Poland to evaluate environmental factors and male fertility. Participants were interviewed and provided a semen sample. The Y:X ratio was assessed by fluorescent in situ hybridization (FISH). Air quality data were obtained from the AirBase database. In multivariate analysis the significant reduction was observed in the proportion of Y/X chromosome bearing sperm and exposure to particulate matter >10 µm in aerodynamic diameter PM10 ( p = .009) and particulate matter <10 µm in aerodynamic diameter PM2.5 ( p = .023). The observed effects of a lower Y:X sperm chromosome ratio among men exposed to air pollution support the evidence that the trend of declining sex ratio in several societies over past decades has been due to exposure to air pollution; however due to limited data on this issue, the obtained results should be confirmed in longitudinal studies.

[High risk of atherosclerosis in men aged 20-39 from Lodz agglomeration]. / Wysokie ryzyko wystapienia miazdzycy u mezczyzn w wieku 20-39 lat z aglomeracji lódzkiej.

THE AIM OF THE STUDY: To estimate the incidence of atherosclerosis risk factors in young men of Lodz city because of the highest in Poland fatality rate of circulatory system diseases. MATERIAL AND METHODS: Anamnestic data on actual diseases, smoking, alcohol drinking and physical activity were achieved from 80 men, volunteers aged 20-39 years. Body weight and height, waist and hip circumference and arterial blood pressure were measured. Blood levels of lipids: total cholesterol (TCh), its fractions LDL, and HDL (LDL-Ch, HDL-Ch) ,and triglicerydes (TG), glucose, albumins, sex hormone binding globulin (SHBG), FSH, LH, total testosterone, dehydroepiandrosterone sulphate (DHEA-S) and estradiol were determined. Calculated were body mass index (BMI), waist to hip ratio (WHR), free testosterone index (FTI), free and bioactive testosterone. RESULTS: At least 3 atherosclerosis risk factors were simultaneously found in 33.7% of men, of which 22.7% were 20-29-year-old and 47.2% 30-39-year-old subjects. Elevated values of TG were found in 16.2% of men, TCh in 13.7%, LDL-Ch in 7.5% and decreased values of HDL-Ch in 6.2%. Positive significant correlations were found between WHR and TCh (R = 0.39; p = 0.01), LDL-Ch (R = 0.38; p = 0.02), TG (R = 0.41; p = 0.009). WHR negatively correlated with HDL-Ch (R = -0.31; p = 0.04). 50% of men had the excessive body weight. Obese men had abdominal type of obesity in 90%. As many as 62% of subjects had excessive systolic and 21% excessive diastolic arterial blood pressure. Blood pressure positively correlated with body weight (R = 0.51; p < 0.001), BMI (R = 0.51; p < 0.001), waist circumference (R = 0.55; p < 0.001) and WHR (R = 0.44; p < 0.001). In the whole group 35% of subjects led sitting life style and did not report any other physical activity. 57.5% of men were present or past smokers. 44% of men consumed alcohol everyday or almost everyday. FTI diminished with the advancing age, what was connected with the increase in SHBG blood concentration. There were no changes in total, free or bioactive testosterone, or LH and FSH concentrations with the age. Correlations between androgens and lipid profiles were not found. Estradiol blood levels negatively correlated with TG (R = -0.35; p = 0.03) and was significantly lower in 30-39-year-old men than in younger (20-29). CONCLUSION: The results indicate considerably higher incidence of atherosclerosis risk factors in young men, citizens of Lodz agglomeration, than it was found before for other regions of Poland. This phenomenon increases with the advancing age already between 20 and 39 years. Implementation of intensive prophylactic actions may prevent it.

Cell-free fetal DNA testing in prenatal diagnosis: Recommendations of the Polish Gynecological Society and the Polish Human Genetics Society.

This paper contains a joint position of the Polish Gynecological Society and Polish Human Genetics Society on the cell-free fetal DNA testing in prenatal diagnosis. We present situations where the cell-free fetal DNA testing should be applied and cases in which performing of the test is not useful. We indicate what diagnostic steps should be performed before the test and how the test results should be interpreted and followed.

[Nasal bone biometry in the second trimester of gestation]. / Biometria nosa plodu w drugim trymestrze ciazy.

OBJECTIVES: To determine physiological variability range of the analyzed biometrical parameters and to establish optimal circumstances for fetal nasal ultrasound biometry. To evaluate preliminarily the value of fetal nasal biometry in the screening for aneuploidy. DESIGN: Ultrasound measurement of nasal bones length and nasal width in healthy fetuses and in fetuses with common aneuploidies. MATERIALS AND METHODS: Measurements of the analyzed parameters were undertaken in 681 euploid fetuses and 9 fetuses with common aneuploidies. Nasal bones length was measured with accordance to the same set of rules as determined by Cicero et al. in their publication relating to the first trimester nasal bones assessment. Nasal width was measured in the coronal plane between the alae. RESULTS: Relationship between the examined parameters and gestational age was described. The normal variability range of the analyzed parameters was determined and percentile charts created. In three out of five examined fetuses with trisomy 21 the nasal bones length was below the 5th percentile. In one out of five trisomy 21 fetuses the nasal width was over the 95th percentile. Regrettably the paucity of data obtained from affected fetuses does not allow drawing statistically founded conclusions. CONCLUSIONS: Fetal nasal biometry seems to be a valuable screening marker of trisomy 21 in the second trimester, requiring further studies.

[Prenatal ultrasound findings in complete trisomy 9]. / Regularna trisomia 9 chromosomu--opis przypadku, przeglad pismiennictwa.

This case report describes a 40-year-old woman, primigravida. On 13,3 weeks of gestation we diagnosed an abnormal flow pattern in the umbilical artery and abnormal hyperechogenic structure in fetal abdomen. In next sonographic examination on 16 weeks of gestation we diagnosed ventriculomegaly and ahydramnion. We also observed spina bifida, hyperechogenic kidneys, abnormal flow pattern in the umbilical vein and pulmonary valve insufficiency. We performed genetic amniocentesis. We observed complete trisomy in cytogenetic examinations. The woman opted for an elective TOP according to the Polish Abortion Act on 20 weeks of gestation.

Folate status, regulatory T cells and MTHFR C677T polymorphism study in allergic children.

PURPOSE: This study aimed to investigate early-life folate serum concentrations in children with food, inhalant or mixed type allergy. The influence of folate levels on the FoxP3 expression in Treg (regulatory T) cells in the studied children, taking into account the MTHFR (5,10-methylenetetrahydrofolate reductase) genotypes was also analyzed. MATERIAL AND METHODS: The study was performed in 83 allergic children (study group) and 49 healthy children (control group), aged 2-72 months. Medical history of each child was obtained and laboratory tests (serum folic acid concentrations and MTHFR C677T polymorphism) were carried out. The percentage of Treg cells was evaluated in almost a half of the examined subjects (48.5%). RESULTS: Significantly higher serum folate levels in the group of children with food allergy than in those with inhalant allergy was confirmed (P=0.037). In the study group the TT homozygotes were characterized by significantly lower folate concentrations than CC homozygotes (P=0.045). A negative correlation was demonstrated between the FoxP3 expression in CD4+CD25highFoxP3+ peripheral blood lymphocytes and serum folic acid concentrations. The correlation was more pronounced in the group of allergic children and it was statistically significant (r=-0.339, P<0.05). CONCLUSIONS: The results of the study indicate a possibility of some effects of folate status on Treg cells, thus suggesting their potential role in the development and course of allergy in children.

Dietary Patterns and the Frequency of Disomy in Human Sperm.

OBJECTIVES: To determine whether dietary patterns are associated with the frequency of sperm aneuploidy in a human sperm. It was shown that the role of nutrition, especially dietary pattern, remains unexamined as a risk factor in sperm aneuploidy. In contrast to the traditional analytical approach used in nutritional epidemiology, dietary pattern analysis considers overall diet rather than individual nutrients or foods. METHODS: The study population consisted of 212 men who were attending an infertility clinic for diagnostic purposes and who had semen concentration of ≥15 (10(6)/ml) (World Health Organization, 2010). Sperm aneuploidy was assessed using multicolor fluorescent in situ hybridization (DNA probes specific for chromosomes 13, 18, 21, X, Y). Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Men were classified into 3 groups according to scores of each dietary pattern: Western, Mixed, Prudent. RESULTS: In multivariate analysis, Prudent dietary pattern characterized by high intakes of fish, chicken, fruit, cruciferous vegetables, tomatoes, leafy green vegetables, legumes, and whole grains decreases disomy of chromosomes XX and 21 (P = .01 and P = .005) compared with Western dietary pattern characterized by high intakes of red and processed meat, butter, high fat dairy, refined grains, pizza, snacks, high-energy drinks, and sweets. CONCLUSION: Higher consumption of Prudent dietary pattern was associated with decreased frequencies of sperm disomy. As this is the first study to analyze the relation of diet and the frequency of sperm aneuploidy, our findings merit further studies, in other populations.