Disorders of sex development (DSD) are a group of rare conditions characterized by discrepancy between chromosomal sex, gonads and external genitalia. Congenital abnormalities of the kidney and ...urinary tract are often associated with DSD, mostly in multiple malformation syndromes. We describe the case of an 11-year-old Caucasian boy, with right kidney hypoplasia and hypospadias. Genome-wide copy number variation (CNV) analysis revealed a unique duplication of about 550 kb on chromosome Xq27, and a 46,XX karyotype, consistent with a sex reversal phenotype. This region includes multiple genes, and, among these,
emerged as the main phenotypic driver. This is the fifth case reporting a genomic imbalance involving the
gene in a 46,XX SRY-negative male, and the first with associated renal malformations. Our data provide plausible links between
gene dosage and kidney malformations. It is noteworthy that the current and reported
gene duplications are below the detection threshold of standard karyotypes and were found only by analyzing CNVs using DNA microarrays. Therefore, all 46,XX SRY-negative males should be screened for
gene duplications with DNA microarrays.
Globozoospermia is a rare but severe teratozoospermia, characterized by ejaculates consisting completely of round-headed spermatozoa that lack an acrosome or, in partial globozoospermia, containing a ...variable proportion (20.0-90.0%) of acrosomeless spermatozoa. Men that are affected with total globozoospermia are infertile, and even the application of intracytoplasmic sperm injection (ICSI) has met with disappointingly low success rates. In humans, several case reports of globozoospermia have demonstrated that two or more siblings were affected in each family, which suggested a genetic component to this disease. Currently, three genes are known to be associated with total globozoospermia in humans, SPATA16 , PICK1 and DPY19L2 genes. Mutations in SPATA16 and PICK1 are rare causes of globozoospermia, found in only one patient each. Several studies have suggested that DPY19L2 mutations are the major cause of globozoospermia in patients from different ethnic origins and different geographic regions. The most common DPY19L2 mutation is the 200 kb deletion arising from a nonallelic homologous recombination (NAHR) between the flanking low copy repeats (LCRs). Here we describe the presence of a homozygous deletion of the DPY19L2 gene in two infertile Macedonian patients with 100.0% round headed spermatozoa, thus suggesting that this deletion represents a major cause of globozoospermia among Macedonian men.
Summary
The aim of this study was to examine whether there is an association among genetic variability in leptin (LEP) and leptin receptor (LEPR) genes and male infertility. We performed a ...case–control study and were searching for an association between polymorphisms of LEP and LEPR genes and male infertility. The study group consisted of 317 patients with idiopathic infertility and a control group of 241 fertile men from Slovenia. Four single nucleotide polymorphisms (SNPs) in LEP gene and four single nucleotide polymorphisms (SNPs) in LEPR gene were chosen and genotyped. Statistically significant SNP was further validated in additional 255 infertile patients and 168 controls from Serbia and Macedonia. In the Slovenian population, we found a statistically significant difference in genotype distribution for rs10244329 polymorphism in LEP gene (recessive genotype model, p value = 0.048). The trend toward statistically significant difference in genotype distribution for rs10244329 polymorphism was confirmed in the Serbian and Macedonian populations (p value = 0.07). Our data suggest that genetic variability in the LEP gene might be associated with male infertility warranting further confirmation and mechanistic investigations.
Cytochrome
(
) is an enzyme of great importance for the metabolism of clinically used drugs. More than 100 variants of the
gene have been identified so far. The aim of this study was to investigate ...the allele distribution of
gene variants in 100 individuals of each of the Macedonian, Albanian and Romany population, by genotyping using long range polymerase chain reaction (PCR) and a multiplex single base extension method. The most frequent variants and almost equally distributed in the three groups were the fully functional alleles
and
. The most common non functional allele in all groups was
that was found in 22.5% of the Albanians. The most common allele with decreased activity was
which was found in 23.0% of the Romany ethnic group, in 11.0% of the Macedonians and in 10.5% of the Albanians. Seven percent of the Albanians, 6.0% of the Romani and 4.0% of the Macedonians were poor metabolizers, while 5.0% of the Macedonians, 1.0% of Albanians and 1.0% of the Romanies were ultrarapid metabolizers. We concluded that the
gene locus is highly heterogeneous in these groups and that the prevalence of the
allele variants and genotypes in the Republic of Macedonia is in accordance with that of other European populations.
Molar pregnancy is a gestational trophoblastic disease that belongs to the category of precancerous lesions. On the other end of the spectrum are gestational trophoblastic neoplasms such as invasive ...mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor, which are considered malignant tumors. Based on defined histopathological criteria, molar pregnancy is divided into partial and complete hydatidiform mole. Especially in the case of early complete mole, the diagnosis can be quite challenging and often necessitates additional molecular or immunohistochemical methods. The aim of this study was to assess the importance of additional molecular and immunohistochemical methods to accurately diagnose complete hydatidiform mole and to stress the importance of correct diagnosis and close follow-up of these patients. A total of 367 consecutive cases of spontaneous abortion were analyzed in a 3-year period. Eight cases with histopathological diagnosis of complete molar pregnancy were selected for further analysis. Apart from standard microscopic analysis, additional molecular and immunohistochemical analyses were performed in all eight cases. Most of the histopathological characteristics of complete molar pregnancy were present in all cases, together with complete absence of positivity for the p57 immunohistochemical marker in the cytotrophoblasts and villous stromal cells. The molecular analysis revealed androgenetic diploidy in seven cases and biparental diploidy in one case with more than three consecutive complete molar pregnancies. Additional immunohistochemical and molecular methods can considerably aid in the correct diagnosis of molar pregnancy.
Hearing impairment is the most common sensory deficit in humans affecting 1 in 1000 newborns. When present in an infant, deafness may have dramatic effects on language acquisition, seriously ...compromising the quality of their life. Deafness is influenced by both genetic and environmental factors, with inherited causes as the most prominent etiological factor in deafness in developed countries. The genetic basis of hearing loss is complex with numerous loci and genes underlying hereditary sensoryneural non syndromic hearing loss (NSHL) in humans. Despite the wide functional heterogeneity of the genes, mutations in the GJB2 gene are found to be the most common cause of sporadic and recessive NSHL in many populations worldwide. Molecular characterization of deafness in the Republic of Macedonia was performed in 130 NSHL profoundly deaf children from different ethnic origins. Molecular studies included direct sequencing of the GJB2 gene and specific polymerase chain reaction (PCR) analyses for the del(GJB6- D13S1830) mutation. Five common mitochondrial DNA (mtDNA) mutations A1555G, 961delT+ C(n), T1095C, C1494T and A827G were also analyzed using the SNaPShot method. In preliminary studies, GJB2 gene mutations were found in 36.4% of analyzed patients, with predominance of 35delG in Macedonian and Albanian patients and W24X in Gypsy patients, respectively. No del(GJB6- D13S1830) mutation was found. None of the analyzed deafness-associated mutations in mtDNA were identified in the studied patients
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