Genetic and biologic risk factors associated with hernia formation: A review.

BACKGROUND: This systematic review aims to identify genetic and biologic markers associated with abdominal hernia formation. METHODS: Following PRIMSA-guidelines, we searched PubMed, MEDLINE, Embase, Scopus, and COCHRANE databases. RESULTS: Of 5946 studies, 65 were selected, excluding parastomal hernias due to insufficient data. For inguinal hernias, five studies unveiled 92 susceptible loci across 66 genes, predominantly linked to immune responses. Eleven studies observed elevated MMP-2 levels, with seven highlighting greater MMP-2 in direct compared to indirect inguinal hernias. One incisional hernia study identified unique gene-expression profiles in 174 genes associated with inflammation and cell-adhesion. In hiatal hernias, several genetic risk loci were identified. For all hernia categories, type I/III collagen ratios diminished. CONCLUSIONS: Biological markers in inguinal hernias appears consistent. Yet, the genetic predisposition in incisional hernias remains elusive. Further research to elucidate these genetic and biological intricacies can pave the way for more individualized patient care.

Sex-based differences in inguinal hernia factors.

BACKGROUND: Much of our knowledge about inguinal hernias is based on males. Meanwhile, it is established that women have worse outcomes after inguinal hernia repair, with more chronic pain and higher recurrences. Pediatric literature shows inguinal hernias in females are more likely to be bilateral, incarcerated, and carry a stronger genetic predisposition than males. We aimed to evaluate sex-based differences in inguinal hernia factors in adults, to help supplement the paucity of literature in the adult population. METHODS: An institutional database of patients undergoing repair of primary inguinal hernias was queried with focus on preoperative risk factors and operative characteristics. Multivariate analysis was performed looking for independent variables associated with a greater number of hernia defects found intraoperatively. RESULTS: Among 494 patients, 202 (40.9%) were female. Number of risk factors among females was significantly higher than males (1.53 vs 1.2, p = 0.003). Females had significantly more constipation, GERD, and asthma and lower BMI than males. Family history of hernias was similar between both sexes. As expected, females had significantly less direct hernias (12.9% vs 32.9%, p < 0.001) and more femoral hernias (38.5% vs 12.2%, p < 0.001) than males. Bilaterality was similar. Females undergoing inguinal hernia repair averaged 1.23 prior deliveries. Regression analysis showed age, sex, BMI, and number of deliveries were not correlated with the number of defects. CONCLUSIONS: Females undergoing primary inguinal hernia repair had more preoperative risk factors for inguinal hernia than males. In our population, there was no higher incidence of bilaterality or significant genetic predisposition in females as noted by family history of hernias. Age, sex, BMI and number of deliveries did not correlate with the number of hernia defects found. Our study promotes awareness of inguinal hernias in females and presents new data to quantify sex-based differences and predispositions to inguinal hernias.

Sex-specific genetic variants associated with adult-onset inguinal hernia in a Taiwanese population.

Introduction: Inguinal hernia repair is one of the most common surgeries worldwide. However, there is limited information on its underlying genetic mechanism. Studies on the genetic factors related to inguinal hernia in Han Chinese are lacking. Therefore, we aimed to conduct a hospital-based study to assess the genetic factors and comorbidities underlying inguinal hernia in Taiwan. Materials and Methods: This was a retrospective case-control study. Utilizing data from the Taiwan Precision Medicine Initiative, we identified 1000 patients with inguinal hernia and 10,021 matched controls without inguinal hernia between June 2019 and June 2020. Four susceptibility loci (rs2009262, rs13091322, rs6991952, and rs3809060) associated with inguinal hernia were genotyped by the Taiwan Biobank version 2 (TWBv2) array. Inguinal hernia, surgery types, and comorbidities were obtained from the electronic health records of Taichung Veterans General Hospital. Results: Adult-onset inguinal hernia was associated with WT1 rs3809060 GT/TT genotype in males and EFEMP1 rs2009262 TC/CC genotype in females. In addition, we identified sex-specific risk factors associated with inguinal hernia; benign prostatic hyperplasia in males (OR: 3.19, 95% CI: 2.73 - 3.73, p< 0.001), chronic obstructive pulmonary disease in females (OR: 2.34, 95% CI: 1.33 - 4.11, p = 0.003) and overweight, defined by body mass index ≧24 kg/m2 (OR: 0.75, 95% CI: 0.65 - 0.86, p<0.001 in males, and OR: 0.60, 95% CI:0.37 - 0.98, p = 0.042 in females), were inversely associated with inguinal hernia. After stratifying BMI, overweight males with EFEMP1 rs2009262 TC/CC genotype exhibited a higher risk of inguinal hernia (OR: 1.31, 95% CI: 1.07 - 1.61, p = 0.01). Additionally, rs3809060 was specifically associated with male patients with direct-type inguinal hernia (OR: 1.62, 95% CI: 1.19 - 2.22, p = 0.002). Conclusion: Genetic susceptibility appears to participate in the pathogenesis of inguinal hernia in the Taiwanese population in a sex-specific manner. Future studies are needed to illuminate the complex interplay between heredity and comorbidities.

The inheritance of groin hernias: an updated systematic review with meta-analyses.

PURPOSE: The aim of this systematic review was to assess the inheritance of groin hernias. METHODS: The primary outcome was to assess the inheritance based on the family history of groin hernias. We included studies that reported family history in patients with groin hernias, assessed the development of groin hernias in patients with a positive family history, or assessed the development of groin hernias in twins. Searches were conducted in PubMed, EMBASE, and Cochrane CENTRAL in November 2021. Results were synthesized narratively and with meta-analyses. RESULTS: Twenty-two studies with unique participants were included. While two twin studies did not show convincing results of a genetic origin in children, database studies with low risk of bias showed that a positive history in parents or siblings increased the risk of inguinal hernia in children, and the risk was highest between mothers and daughters and between sisters. In adults, patients with inguinal hernia had higher odds of having a positive family history compared with patients without groin hernia (odds ratio 5.3, 95% confidence interval 3.3-8.7), and a nationwide study found the highest risk of inguinal hernia repair when a sister had been repaired compared with a brother. This study also found that having a sibling repaired for a groin hernia increased the risk of femoral hernia repair. CONCLUSION: Despite studies being heterogeneous, there is overwhelming evidence that a positive family history is a risk factor for developing inguinal hernia in both children and adults, seemingly with a pronounced female-female inheritance pattern.

Genetic Analysis Reveals Complete Androgen Insensitivity Syndrome in Female Children Surgically Treated for Inguinal Hernia.

Background: Complete androgen insensitivity syndrome (CAIS) is a congenital condition caused by genetic defects in the androgen receptor (AR) gene located on the X chromosome, which lead to a phenotypical female individual with a 46, XY karyotype. Early diagnosis of CAIS is essential for proper clinical management, allows assessment of familial risk and contributes to healthcare decisions. However, diagnosis of CAIS can be overlooked in girls with inguinal hernia, resulting in inappropriate management. Methods: Five female patients from three unrelated families presented to our genetic clinic with primary amenorrhea. Each patient had been diagnosed with inguinal hernia in childhood and had undergone hernia repair without further investigation into what was contained in the hernial sac. We carried out physical examination, cytogenetic studies, hormonal evaluation, and molecular analysis to establish a comprehensive diagnosis. Family history and pedigree were collated to identify at-risk family members. Results: All patients presented with female external genitalia. Cytogenetic studies revealed a 46, XY karyotype and hormonal analysis suggested a diagnosis of CAIS. Sequencing of the AR gene in all patients and suspected family members revealed pathogenic variants in the AR gene and confirmed the molecular diagnosis of CAIS. Conclusions: We report the delayed diagnosis of CAIS in female Indonesian patients with a history of inguinal hernia in childhood. An early diagnosis of CAIS is essential for appropriate clinical management, as well as assessing familial risk. Increasing awareness among clinicians is paramount, and we encourage a CAIS diagnosis to be considered in any patient presenting with female appearance and inguinal hernia.

Matrix Metalloproteinases (MMP-2) and Tissue Inhibitors of Metalloproteinases (TIMP-2) in Patients with Inguinal Hernias.

BACKGROUND: The development of inguinal hernia might be related with collagen metabolism, which was regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The aim of this study was to evaluate the mRNA and protein expression levels of MMP-2 and TIMP-2 in anterior rectus sheath fascia to investigate the function of them in inguinal hernia formation. METHODS: The study enrolled 48 primary inguinal hernia patients: 32 participants had indirect inguinal hernia and 16 patients suffered direct inguinal hernia. Specimens were taken from the anterior rectus sheath fascia. The amounts of MMP-2 mRNA and TIMP-2 mRNA were evaluated by real-time fluorescence quantitative polymerase chain reaction (RT-PCR), and immunohistochemistry was performed to assess the protein expression of them. RESULTS: The mRNA and protein expression levels of MMP-2 in direct group were significantly higher than those of control group (P < 0.05) and indirect group (P < 0.05), while the expression levels of TIMP-2 in direct group were significantly lower than those of control group (P < 0.05) and indirect group (P < 0.05). The ratio of MMP-2 mRNA/TIMP-2 mRNA in direct group was significantly higher than that of control group (P < 0.05) and indirect group (P < 0.05), and the ratio of indirect group was significantly higher than that of control group (P < 0.05). According to receiver operating characteristic (ROC) curve, MMP-2/TIMP-2 can diagnose direct hernia from controls with area under the curve (AUC) of 0.950 and indirect hernia with AUC of 0.730 effectively. CONCLUSIONS: Elevated level of MMP-2 and decreased level of TIMP-2 may play a role in direct inguinal hernia development. The ratio of MMP-2/TIMP-2 may be useful in identification of direct hernia.

Comprehensive analysis reveals a six-gene signature and associated drugs in mimic inguinal hernia model.

PURPOSE: Inguinal hernia often occurs in elderly men, and more than one in five men will undergo inguinal hernia repair during their lifetime. Nevertheless, the underlying molecular mechanisms of the pathogenesis behind hernia formation is still unclear. The aims in this study are finding out the potential gene markers and available drugs. METHODS: Firstly, we re-analyzed the GSE92748 datasets, including four high and four low expressions of humanized aromatase transgenic mice, which refers to mimic humanized hernia, to identify differentially expressed genes (DEGs) in AromhumH group compared with AromhumL group by the criteria: fold change ≥ 1.4 and adjust P value < 0.05. Secondly, the gene ontology and signaling pathway enrichment analyses of these DEGs were performed through online databases. In addition to the protein and protein interaction networks among these DEGs were constructed and the significant gene modules were chosen for further gene-drug interaction analysis. Lastly, the existing drugs target to these module genes were screen to explore the therapeutic effect for treatment of hernia. RESULTS: We have identified 64 DEGs, which were associated with muscle system process, actomyosin structure organization etc. Moreover, the significant module genes in PPI networks were Cmya1, Casq2, Cmya5, Ttn, Csrp3 and Actc1, and one existing drug, DEXAMETHASONE, have targeted to Actc1 gene. CONCLUSIONS: In the paper, we identified 6 potential genes and one existing drug for inguinal hernia, which might be used as targets and drugs for the study of inguinal hernia.

Whole-exome sequencing identifies a potential TTN mutation in a multiplex family with inguinal hernia.

PURPOSE: Inguinal hernia repair is one of the most common procedures in general surgery. Males are seven times more likely than females to develop a hernia and have a 27 % lifetime 'risk' of inguinal hernia repair. Several studies have demonstrated that a positive family history is an important risk factor for the development of primary inguinal hernia, which indicates that genetic factors may play important roles in the etiology of the disease. So far, the contribution of genetic factors and underlying mechanisms for inguinal hernia remain largely unknown. The aim of this study was to investigate a multiplex Estonian family with inguinal hernia across four generations. METHODS: The whole-exome sequencing was carried out in three affected family members and subsequent mutation screening using Sanger sequencing was performed in ten family members (six affected and four unaffected). RESULTS: Whole-exome sequencing in three affected family members revealed a heterozygous missense mutation c.88880A>C (p.Lys29627Thr; RefSeq NM_001256850.1) in the highly conserved myosin-binding A-band of the TTN gene. Sanger sequencing demonstrated that this mutation cosegregated with the disease in this family and was not present in ethnically matched control subjects. CONCLUSION: We report that missense variant in the A-band of TTN is the strongest candidate mutation for autosomal-dominant inguinal hernia with incomplete penetrance.

Effects of the SLCO1B1 *1 and SLCO1B1 *5 polymorphisms on IL-6 and IL-10 levels in patients under pravastatin treatment prior to inguinal hernia repair.

BACKGROUND: Different genetic variants in the SLCO1B1 gene have been shown to have functional importance in individual variability in pravastatin pharmacokinetics, resulting in different inflammatory responses to surgical inguinal hernia repair. The aim of this study was to determine IL-6 and IL-10 serum concentrations in the presence and absence of the SLCO1B1*1 and SLCO1B1*5 polymorphisms in patients under pravastatin treatment that underwent inguinal hernia repair. METHODS: The study included 26 subjects that were under pravastatin treatment (40 mg/day) at least 1 month prior to inguinal hernia repair open technique. All the subjects were genotyped for the SLCO1B1*1 and SLCO1B1*5 polymorphisms through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and their preoperative and postoperative serum IL-6 and IL-10 levels were quantified through the ELISA technique. The IL-6 and IL-10 levels were analyzed in the presence or absence of the mutated polymorphism for SLCO1B1*1 and SLCO1B1*5. RESULTS: The SLCO1B1*1 polymorphism had a frequency of 38.5% and the SLCO1B1*5 polymorphism had a frequency of 19.2%. The preoperative and postoperative serum concentrations of IL-6 were 0.252 pg/ml ± 0.19 and 0.206 pg/ml ± 0.20, respectively, with a p = 0.525, whereas the preoperative and postoperative serum concentrations for IL-10 were 4.943 pg/ml ± 3.13 and 4.611 pg/ml ± 3.01, respectively, with a p = 0.004. CONCLUSIONS: The patients under pravastatin treatment presented with lower postoperative IL-10 levels with respect to the baseline concentration (p = 0.004), regardless of the presence or absence of the two polymorphisms.

Genetic analysis of the TBX2 gene promoter in indirect inguinal hernia.

PURPOSE: Inguinal hernia is a common disease, majority of which are indirect inguinal hernia (IIH). A positive family history indicates that genetic factors play important roles in the IIH development. To date, genetic causes for IIH remain unknown. T-box transcription factor 2 (TBX2) is a major regulator in the morphogenesis and organogenesis. The human TBX2 gene is widely expressed in fetal and adult tissues, including muscle and connective tissues. Therefore, we speculated that altered TBX2 gene expression may be involved in the IIH formation. METHODS: IIH patients (n = 129) and ethnic-matched healthy subjects (n = 198) were recruited for this study. The human TBX2 gene promoters were generated with PCR and directly sequenced to identify DNA sequence variants (DSVs). Furthermore, biological functions of the DSVs were examined with reporter gene constructs in cultured cells. RESULTS: Total six DSVs within the TBX2 gene promoter were identified. A heterozygous DSV (g.59476307G>C) was identified in an IIH patient, but in none of controls, which significantly decreased the TBX2 gene promoter activities. Another heterozygous DSV (g.59476704G>C) was only found in one control, which did not affect TBX2 gene promoter activities. Four DSVs, g.59476316C>A (rs73991913), g.59476415T>C (rs1476781), g.59476510G>C (rs4455026) and g.59476892C>T (rs2286524), all of which were single nucleotide polymorphisms, were found in both IIH patients and controls with similar frequencies. CONCLUSIONS: Our data suggested that the DSV within the TBX2 gene promoter was implicated in the IIH development as a rare cause.

Association of collagen type I alpha 1 gene polymorphism with inguinal hernia.

PURPOSE: A positive family history is an important risk factor for inguinal hernia development, suggesting a genetic trait for hernia disease. However, gene mutations responsible for abdominal wall hernia formation in humans have not yet been studied. We aimed to evaluate whether the functional Sp1 binding site polymorphism within intron 1 of the collagen type I, alpha 1 (COL1A1) gene was associated specifically with inguinal hernia disease. METHODS: 85 participants with surgically diagnosed inguinal hernia disease, and 82 physically active controls without any history of connective tissue disease and hernia were recruited for this case-control genetic association study. Polymerase chain reaction and restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to detect these polymorphisms. RESULTS: Significantly, more patients gave a positive family history for an inguinal hernia compared to healthy controls (OR 3.646, 95 % CI 1.375-9.670, P = 0.006). COL1A1 Sp1 SNP (rs 1800012) was identified. Results demostrated statistically significant deviation from HWE for cases (P = 0.007), but not for the controls (P = 0.276). Our results revealed an increased frequency of COL1A1 Sp1 Ss genotype in inguinal hernia patients (OR 3.593, 95 % CI 1.867-6.915, P = 0.000). CONCLUSIONS: This results suggest that polymorphism of the COL1A1 Sp1 binding site is associated with an increased risk for developing inguinal hernias. So, rs 1800012 locus is a potential candidate region for susceptibility in molecular mechanism of inguinal hernia pathophysiology.

A case of 46, XY DSD presenting as a crossed ectopic gonad with a contralateral sliding inguinal hernia.

A three-month-old boy was referred to our facility for the treatment of a right impalpable testis, left inguinal hernia, and penoscrotal hypospadias with asymmetric external genitalia. The left gonad was palpated in the left scrotum. The chromosomal study revealed a normal male 46, XY karyotype. Operative findings showed that the right streak gonad, uterus, and fallopian tubes were in the wall of the left hernia sac, forming a sliding hernia. Laparoscopy confirmed that the right gonadal vessels had crossed to the left internal inguinal ring. Herniorrhaphy was done and the right streak gonad, uterus, and fallopian tubes were excised. An exploration of the left gonad revealed an ovotestis. The ovary was removed, and a left testicular biopsy was simultaneously performed. A one-stage hypospadias repair using Koyanagi procedure was also performed. The pathological findings showed an ovarian stroma in the right gonad and left ovary. Only Sertoli cells were detected in the biopsied specimen from the left testis.

Transverse testicular ectopia with abnormal karyotype - a case report.

OBJECTIVES: Growth disturbances and developmental malformations of external genitalia, such as hypospadias, bifid scrotum and micropenis, coexisting with non-palpable testes, may develop as a result of primary endocrinological dysfunctions as well as an effect secondary to chromosomal aberrations. Therefore, patients with these symptoms require specific diagnostic and therapeutic approaches. DESIGN AND METHODS: We present an example of TTE as a presentation of karyotype abnormalities. Clinical presentation - 9.5 year old boy presented with hypospadias, bilateral cryptorchidism and right inguinal hernia and short stature. RESULTS: Endocrine test showed low testosterone levels with adequate gonadal response. Laparoscopy was performed and revealed the presence of TTE. CONCLUSIONS: The presence of mosaic karyotype with abnormal Y chromosome does not exclude a possibility of testis migration disorders, including TTE, caused by other (possibly genetic) factors. Laparoscopy is a technique of choice for diagnosis and treatment in cases of cryptorchidism.

The International Testicular Cancer Linkage Consortium: a clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred.

OBJECTIVES: Familial aggregation of testicular germ cell tumor (TGCT) has been reported, but it is unclear if familial TGCT represents a unique entity with distinct clinicopathologic characteristics. Here we describe a collection of familial TGCT cases from an international consortium, in an effort to elucidate any clinical characteristics that are specific to this population. MATERIALS AND METHODS: Families with >or=2 cases of TGCT enrolled at 18 of the sites participating in the International Testicular Cancer Linkage Consortium were included. We analyzed clinicopathologic characteristics of 985 cases from 461 families. RESULTS: A majority (88.5%) of families had only 2 cases of TGCT. Men with seminoma (50% of cases) had an older mean age at diagnosis than nonseminoma cases (P = 0.001). Among individuals with a history of cryptorchidism, TGCT was more likely to occur in the ipsilateral testis (kappa = 0.65). Cousin pairs appeared to represent a unique group, with younger age at diagnosis and a higher prevalence of cryptorchidism than other families. CONCLUSIONS: Clinicopathologic characteristics in these familial TGCT cases were similar to those generally described for nonfamilial cases. However, we observed a unique presentation of familial TGCT among cousin pairs. Additional studies are needed to further explore this observation.

Risk factors for early recurrence after inguinal hernia repair.

BACKGROUND: Family history, male gender and age are significant risk factors for inguinal hernia disease. Family history provides evidence for a genetic trait and could explain early recurrence after inguinal hernia repair despite technical advance at least in a subgroup of patients. This study evaluates if age and family history can be identified as risk factors for early recurrence after primary hernia repair. METHODS: We performed an observational cohort study for 75 patients having at least two recurrent hernias. The impact of age, gender and family history on the onset of primary hernias, age at first recurrence and recurrence rates was investigated. RESULTS: 44% (33/75) of recurrent hernia patients had a family history and primary as well as recurrent hernias occurred significantly earlier in this group (p = 0.04). The older the patients were at onset the earlier they got a recurrent hernia. Smoking could be identified as on additional risk factor for early onset of hernia disease but not for hernia recurrence. CONCLUSION: Our data reveal an increased incidence of family history for recurrent hernia patients when compared with primary hernia patients. Patients with a family history have their primary hernias as well as their recurrence at younger age then patients without a family history. Though recurrent hernia has to be regarded as a disease caused by multiple factors, a family history may be considered as a criterion to identify the risk for recurrence before the primary operation.

Looking past the lump: genetic aspects of inguinal hernia in children.

Inguinal hernia is associated with a multitude of genetic syndromes. Disorders of the microfibril, elastin, collagen, and the glycosaminoglycan component of the extracellular matrix can result in an increase in the likelihood of inguinal hernia. In addition, inguinal hernia may be the presenting feature of disorders of sexual differentiation. Inguinal hernia of unknown etiology also occurs more commonly in several other groups of genetic diseases including chromosomal disorders, microdeletion disorders such as 22q11.2 microdeletion, and in single gene disorders. We review the genetics of connective tissue formation and focus on a series of genetic conditions that may present with or are characterized by a higher risk of inguinal hernia. A comprehensive review of the literature aims to provide a diagnostic framework to aid in the identification of patients with inguinal hernia as part of underlying genetic disease.

Association and haplotype analyses of positional candidate genes in five genomic regions linked to scrotal hernia in commercial pig lines.

Scrotal hernia in pigs is a complex trait likely affected by genetic and environmental factors. A large-scale association analysis of positional and functional candidate genes was conducted in four previously identified genomic regions linked to hernia susceptibility on Sus scrofa chromosomes 2 and 12, as well as the fifth region around 67 cM on chromosome 2, respectively. In total, 151 out of 416 SNPs discovered were genotyped successfully. Using a family-based analysis we found that four regions surrounding ELF5, KIF18A, COL23A1 on chromosome 2, and NPTX1 on chromosome 12, respectively, may contain the genetic variants important for the development of the scrotal hernia in pigs. These findings were replicated in another case-control dataset. The SNPs around the ELF5 region were in high linkage disequilibrium with each other, and a haplotype containing SNPs from ELF5 and CAT was highly significantly associated with hernia development. Extensive re-sequencing work focused on the KIF18A gene did not detect any further SNPs with extensive association signals. These genes may be involved in the estrogen receptor signaling pathway (KIF18A and NPTX1), the epithelial-mesenchymal transition (ELF5) and the collagen metabolism pathway (COL23A1), which are associated with the important molecular characteristics of hernia pathophysiology. Further investigation on the molecular mechanisms of these genes may provide more molecular clues on hernia development in pigs.

USP26 gene variations in fertile and infertile men.

BACKGROUND: The human X chromosome is enriched with testis-specific genes that may be crucial for male fertility. One is the ubiquitin-specific protease 26 (USP26). Five frequent mutations have been identified: 1737G>A, 1090C > T, 370-371insACA, 494T > C and 1423C>T (with the latter three usually detected in a cluster). Their role in infertility is still controversial. This study assesses the association of the most frequent USP26 mutations with male infertility and male infertility etiology factors. METHODS: The study included 300 infertile and 287 fertile men. Data were collected on ethnicity (according to maternal origin) and family history of reproduction. Clinical records from 235 infertile and 62 fertile (sperm bank donors) men were available and summarized. The five mutations were investigated by bioinformatic tools and their frequencies were assessed by restriction analysis. The results were correlated with clinical findings. Segregation of the mutations in four families was analyzed. RESULTS: The five analyzed mutations were detected in 44 men from both fertile and infertile groups. The cluster and the 1090C>T mutations showed the highest frequency among Arabs and Sephardic Jews of the infertile group, respectively. Inheritance studies showed that mutations were not always associated with the infertility trait. Mutations 1090C>T and 1737G>A were significantly associated with a history of inguinal hernia (P = 0.007 and P = 0.043, respectively). The prevalence of inguinal hernia among men with the 1090C > T mutation was 33.3% (5/15 men), higher than that reported in infertile men (6.7%). CONCLUSIONS: Mutation 1090C > T may be a new genetic risk factor for developing inguinal hernia which may be associated with impaired male fertility.

Three novel AMH gene mutations in a patient with persistent mullerian duct syndrome and normal AMH serum dosage.

BACKGROUND: Persistentmullerian duct syndrome (PMDS) is characterized by the presence of uterus, fallopian tubes and the upper part of the vagina in 46,XY patients with perfectly virilized external genitalia. It is mostly caused by mutations of the AMH or AMH type 2 receptor (AMHR2) gene. The AMH serum level is very often low or undetectable in the AMH gene defect and normal in the AMHR2 gene defect. AIM: We investigate an Italian patient, genotypically and phenotypically male, observed at 1 month of age for a right inguinal hernia that at surgery showed the presence of both testes in the same hernial sac and uterus and fallopian tubes in the abdomen. RESULTS: Genetic tests first showed the absence of the common 27-bp deletion in the AMHR2 gene, then the presence of three new sequence variations in the AMH geneleading to the following variants: the p.A405P carried by the paternal allele; the p.G326V plus the p.V508A carried by the maternal allele. CONCLUSIONS: The determination of serum AMH, performed after the genetic analysis, showed a normal level for age, suggesting that these mutations may affect the function and the bioactivity of the hormone and not the secretion rate.