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PubMed1999

1p microdeletion in sibs with minimal phenotypic manifestations.

We report on two sibs with a paracentric inversion of chromosome 1 [inv(1)(p22.3p34.1)] and a small deletion of the same chromosome (p34.1-->p34.3). They presented with learning disabilities and disturbed conduct but lacked the more severe manifestations usually associated with autosomal chromosome deletion. Born to an alcoholic mother and later placed in foster care because of abuse and neglect, the behavior abnormalities they present are likely to be associated with their traumatic postnatal experience. Microscopic deletions without significant morphological phenotypic expression have been described but are rarely reported. Most reported cases of interstitial deletion of 1p had associated malformations and psychomotor retardation. These sibs may represent the first evidence that deletion of 1p34.1-->1p34.3 may have little impact on the phenotype.

Adolescent↗
PubMed2001

Prognostic value of Y deletion analysis. The role of current methods.

Y chromosome microdeletions represent the most frequent genetic alteration in azoospermic and severely oligozoospermic men, and screening for microdeletions in AZFa, b and c are routinely performed in the major andrology and infertility centres. Since patients with Y microdeletions often require intracytoplasmic sperm injection (ICSI), the question of whether the type of the microdeletion present could have prognostic value for the presence of spermatozoa in the ejaculate or in the testes [by testicular sperm extraction (TESE)] is an interesting one. The review of the literature on this topic showed that there is still no clear genotype--phenotype relationship, i.e. similar testicular alterations may be caused by different types of microdeletions, and apparently identical microdeletions may be associated with diverse tubular damage. Even in azoospermic men, the localization of the microdeletion cannot be used as a valid prognostic parameter before TESE--ICSI to identify patients with spermatozoa in their testes. The only finding with absolute negative prognostic value is the presence of complete AZFa--c deletions, which are invariably associated with an absence of spermatozoa. Microdeletions in AZFa or AZFb seem to have promising prognostic value, but more data and gene-specific deletions have to be provided to draw clear conclusions. The absence of a clear genotype--phenotype relationship, and therefore of a prognostic value of Y deletion analysis, is probably due to the current methods used for the screening of the microdeletions. In fact, to date most centres do not use gene-specific markers but instead use anonymous primers that contribute little information to the pathogenic role of the microdeletions.

Gene Deletion↗
PubMed2005

A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS.

A unique heterozygous 3-kb microdeletion within STX16, a closely linked gene centromeric of GNAS, was previously identified in multiple unrelated kindreds as a cause of autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib). We now report a novel heterozygous 4.4-kb microdeletion in a large kindred with AD-PHP-Ib. Affected individuals from this kindred share an epigenetic defect that is indistinguishable from that observed in patients with AD-PHP-Ib who carry the 3-kb microdeletion in the STX16 region (i.e., an isolated loss of methylation at GNAS exon A/B). The novel 4.4-kb microdeletion overlaps with the previously identified deletion by 1,286 bp and, similar to the latter deletion, removes several exons of STX16 (encoding syntaxin-16). Because these microdeletions lead to AD-PHP-Ib only after maternal transmission, we analyzed expression of this gene in lymphoblastoid cells of affected individuals with the 3-kb or the 4.4-kb microdeletion, an individual with a NESP55 deletion, and a healthy control. We found that STX16 mRNA was expressed in all cases from both parental alleles. Thus, STX16 is apparently not imprinted, and a loss-of-function mutation in one allele is therefore unlikely to be responsible for this disorder. Instead, the region of overlap between the two microdeletions likely harbors a cis-acting imprinting control element that is necessary for establishing and/or maintaining methylation at GNAS exon A/B, thus allowing normal G alpha(s) expression in the proximal renal tubules. In the presence of either of the two microdeletions, parathyroid hormone resistance appears to develop over time, as documented in an affected individual who was diagnosed at birth with the 4.4-kb deletion of STX16 and who had normal serum parathyroid hormone levels until the age of 21 mo.

Chromogranins↗
PubMed1995

Use of fluorescence in situ hybridization (FISH) in the diagnosis of DiGeorge sequence and related diseases.

The proximal portion of human chromosome 22q has been implicated in the pathogenesis of a clinically diverse group of conditions including DiGeorge sequence (DGS), velocardiofacial syndrome, and CHARGE association as well as isolated conotruncal heart anomalies. Frequently, overlap in the clinical presentation of these syndromes occurs and, recently, the presence of microdeletions on chromosome 22q11.2 with varying frequencies has been demonstrated in these syndromes. Using fluorescence in situ hybridization (FISH), we assessed 20 consecutive patients who were cytogenetically and clinically evaluated for a suspected syndrome that could be due to a microdeletion of chromosome 22q11.2. After cytogenetic testing and full clinical evaluation, we compared the results by FISH with the final clinical diagnosis and karyotype results. We found that microdeletions of 22q11.2 were detected in three of the five patients who were evaluated for DGS. The three cases with microdeletions appeared clinically to have DGS while the two negative cases were more atypical. High-resolution banding techniques did not detect a microdeletion in any of the cases; however, one of the 20 patients had a translocation between chromosomes 13 and 22. This patient also had a microdeletion of 22q11.2 detected by FISH and clinical features of DGS. None of the patients who were evaluated for disorders related to DGS showed microdeletions. We conclude that FISH is a useful, easily applied technique for the diagnosis of 22q11.2 microdeletion syndromes, particularly DGS. This test may also be useful in genetic counseling and in both prenatal and postnatal diagnoses.

Abnormalities, Multiple↗
PubMed2001

Prognostic value of Y deletion analysis: How reliable is the outcome of Y deletion analysis in providing a sound prognosis?

Y chromosomal microdeletions at the azoospermia factor (AZF) locus have been implicated as one of the major causes of idiopathic male infertility. The availability of intracytoplasmic sperm injection (ICSI) in treating a variety of male infertility has raised the risk of the transmission of Y microdeletions from father to son. In many IVF centres, Y microdeletion analysis has been used as a diagnostic tool for genetic counselling of infertile couples. Presently, the only prognosis that can be derived from Y microdeletion analysis is that the affected male offspring would benefit from proper clinical management of their infertility. Prognoses based on the pattern of Y microdeletions in relation to phenotype are rather subjective and inconclusive because of insufficient data to derive a definitive correlation whose significance can be determined by statistical analysis. Standardization of the number and choice of sequence-tagged sites (STS), whose deletions result in defective spermatogenesis, for the polymerase chain reaction (PCR) analysis of Y microdeletions would enhance its reliability in the interpretation of the results which is crucial for therapeutic decision-making. Furthermore, in-depth understanding of the gene functions in male infertility, especially at the AZF locus, would contribute greatly to the quality of the prognostic value of Y microdeletion analysis.

Chromosome Deletion↗
PubMed2003

[Y chromosome micro-deletion identification in infertile males].

UNLABELLED: Identifying the genetic causes of male infertility is very important, considering they account for 30-50% of reproductive problems among couples. Genetic abnormalities, among which Y chromosome microdeletions are found, are commonly detected in patients with non-obstructive azoospermia (0-4.3%). Most of these patients are eligible for intracytoplasmic sperm injection (ICSI) and this genetic defect can be inherited by male children. OBJECTIVE: Determining the prevalence of microdeletions in the Y chromosome in a group of Mexican patients presenting azoospermia and oligospermia, under treatment in the Infertility Clinics. MATERIALS AND METHODS: This study included 52 infertile men (cases): 36 with non-obstructive azoospermia, and 16 with oligospermia; and 50 men (controls) whose fertility had been validated. The genomic DNA of each individual was obtained from his EDTA and heparin treated blood, and the corresponding karyotype determined. The karyotype was analyzed using G banding techniques. Eighteen markers (STS) corresponding to the chromosome Y long arm (AZFa, b, c, and d zones) were amplified in each DNA sample in all cases--azoospermic, oligospermic and controls--using the PCR method. RESULTS: No chromosomal alterations were detected in the patients, and no Y chromosome microdeletions were detected in control cases. Five azoospermic patients (13.9%) presented microdeletions corresponding to the AZFb, c, and d zones, while no microdeletions were found in oligospermic patients. The frequency of microdeletions found in this study is very similar to that reported for other populations. CONCLUSIONS: This research not only reports the frequency of microdeletions in the Y chromosome in our population, but also contributes to the integration of a DNA bank for patients with idiopathic male infertility, which will be of great use in the search for the causes of this affection.

Adult↗
PubMed2003

Lack of association between Y chromosome haplogroups and male infertility in Japanese men.

The Y chromosome carries several genes involved in spermatogenesis, which are distributed in three regions in the euchromatic part of the long arm, called AZFa (azoospermia factor a), AZFb, and AZFc. Microdeletions in these regions have been seen in 10-15% of sterile males with azoospermia or severe oligozoospermia. The relatively high de novo occurrence of these microdeletion events might be due to particular chromosome arrangements associated with certain Y chromosome haplogroups. To test whether there is any association between Y chromosome types and male infertility, we studied a sample of 84 Japanese oligozoospermic or azoospermic males. The patients were analyzed for the presence of Yq microdeletions and also typed with a battery of unique event polymorphisms (UEPs) to define their Y haplogroups. Six of the infertile patients presented likely pathological microdeletions detectable with the sequence tagged sites (STS) markers used. There was no significant association between Y chromosome haplogroups and the microdeletions. We also compared the Y haplogroup frequencies in our subset sample of 51 idiopathic azoospermia patients with 57 fertile control Japanese males, and did not observe any significant differences. Contrary to previous reports, our data suggest that Y microdeletions and other molecular events causally associated with male infertility in Japan occur independently of the Y chromosome background.

Chromosome Deletion↗
PubMed2001

Screening for deletions in interval D16-22 of the Y chromosome in azoospermic and oligozoospermic Japanese men.

The genetic basis of infertility remains unclear in a majority of infertile men. In this study, the Y chromosome long arm involving the DAZ (deleted in azoospermia) gene was screened in order to evaluate the occurrence of microdeletion in Japanese infertile men. One hundred and fifty-seven infertile Japanese men with azoospermia and oligozoospermia were analyzed for microdeletions in interval D16-22 of the Y chromosome, using polymerase chain reaction with sequence-tagged site markers. Sixteen sets of oligonucleotide primers were synthesized for the polymerase chain reaction, and Southern blot analysis was also performed. The men were divided into five categories on the basis of sperm concentration: functional azoospermia (A; n = 24), azoospermia caused by obstruction (AO; n = 20), oligozoospermia I (OI, sperm concentration less than I x 10(5)/ml; n = 33), oligozoospermia II (OII, sperm concentration less than 1 x 10(6)/ml; n = 30), and oligozoospermia III (OIII, sperm concentration less than 1 x 10(7)/ml; n = 50). Thirty fertile men with a sperm concentration of more than 2 x 10(7)/ml were also analyzed as controls. Microdeletions were identified, in 12 (7.6%) of the 157 infertile men, as follows: 1 man in category A, 1 in category AO, 5 in category OI, 4 in category OII, and 1 in category OIII. No deletion was identified in the fertile men. One common region around sY240 was identified in 11 of the infertile men with microdeletions. This locus may contain specific genes for spermatogenesis. The sperm concentration in the ten oligozoospermic men with microdeletions was below 1 x 10(6)/ml. There were no correlations between the severity of spermatogenic defects and the extent of the microdeletions. These results suggested that genes in the interval D16-22 of the Y chromosome might have important roles in spermatogenesis.

Base Sequence↗
PubMed2003

Cytogenetic and molecular analysis of the Y chromosome: absence of a significant relationship between CAG repeat length in exon 1 of the androgen receptor gene and infertility in Indian men.

The genetic basis of male infertility remains unclear in the majority of cases. Recent studies have indicated an association between microdeletions of the azoospermia factor a (AZFa)-AZFc regions of Yq and severe oligospermia or azoospermia. Increased (CAG)n repeat lengths in the androgen receptor (AR) gene have also been reported in infertile men. Therefore, in order to assess the prevalence of these genetic defects to male infertility, 183 men with non-obstructive azoospermia (n = 70), obstructive azoospermia (n = 33), severe oligospermia (n = 80) and 59 fertile men were examined cytogenetically and at molecular level for Yq deletions, microdeletions, and AR-CAG repeat lengths along with hormonal profiles [luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T)]. We used high resolution cytogenetics to detect chromosome deletions and multiplex polymerase chain reaction (PCR) involving 27 sequence-tagged site (STS) markers on Yq to determine the rate and extent of Yq microdeletions. PCR amplification with primers flanking exon 1 of AR gene was used to determine the AR-(CAG)n repeat lengths. Hormonal profiles (LH, FSH and T levels) were also analysed in infertile and fertile men. Testicular biopsies showed Sertoli cell only (SCO) morphology, maturation arrests (MA) and hypospermatogenesis. No chromosome aberrations were found in infertile men but there was a significant increase (p < 0.001) in the association of acrocentric chromosomes including the Y chromosome. Yq microdeletions were found in 16 non-obstructive azoospermic men (16 of 70; 22%) and seven severe oligospermic individuals (seven of 80; 8.7%) and most of them had deletions in the sY240 locus. No Yq microdeletions were detected in patients with obstructive azoospermia. No statistically significant difference in the mean length of CAG repeats in AR gene was observed between infertile and fertile men (22.2 +/- 1.5 and 21.5 +/- 1.4 respectively). No significant increase or decrease in levels of LH, FSH and T was observed in infertile and fertile men. In some infertile men, significantly elevated levels of FSH alone or in combination with LH were found to be indicative of failure of spermatogenesis and/or suggestive of testicular failure. Y-chromosome microdeletions contribute to infertility in some patients but no relationship could be established with the (CAG)n repeat lengths in exon 1 of the AR gene in infertile Indian men.

Adenine↗
PubMed2005

Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.

We identified 266 individuals with intragenic NSD1 mutations or 5q35 microdeletions encompassing NSD1 (referred to as "NSD1-positive individuals"), through analyses of 530 subjects with diverse phenotypes. Truncating NSD1 mutations occurred throughout the gene, but pathogenic missense mutations occurred only in functional domains (P < 2 x 10(-16)). Sotos syndrome was clinically diagnosed in 99% of NSD1-positive individuals, independent of the molecular analyses, indicating that NSD1 aberrations are essentially specific to this condition. Furthermore, our data suggest that 93% of patients who have been clinically diagnosed with Sotos syndrome have identifiable NSD1 abnormalities, of which 83% are intragenic mutations and 10% are 5q35 microdeletions. We reviewed the clinical phenotypes of 239 NSD1-positive individuals. Facial dysmorphism, learning disability, and childhood overgrowth were present in 90% of the individuals. However, both the height and head circumference of 10% of the individuals were within the normal range, indicating that overgrowth is not obligatory for the diagnosis of Sotos syndrome. A broad spectrum of associated clinical features was also present, the occurrence of which was largely independent of genotype, since individuals with identical mutations had different phenotypes. We compared the phenotypes of patients with intragenic NSD1 mutations with those of patients with 5q35 microdeletions. Patients with microdeletions had less-prominent overgrowth (P = .0003) and more-severe learning disability (P = 3 x 10(-9)) than patients with mutations. However, all features present in patients with microdeletions were also observed in patients with mutations, and there was no correlation between deletion size and the clinical phenotype, suggesting that the deletion of additional genes in patients with 5q35 microdeletions has little specific effect on phenotype. We identified only 13 familial cases. The reasons for the low vertical transmission rate are unclear, although familial cases were more likely than nonfamilial cases (P = .005) to carry missense mutations, suggesting that the underlying NSD1 mutational mechanism in Sotos syndrome may influence reproductive fitness.

Amino Acid Sequence↗
PubMed2007

Clinical correlation of chromosome 22q11.2 fluorescent in situ hybridization analysis and velocardiofacial syndrome.

OBJECTIVE: To identify characteristics associated with microdeletions of chromosome 22q11.2 ascertained by fluorescent in situ hybridization (FISH) analysis in patients with velopharyngeal insufficiency (VPI), cleft palate, or other clinical features of velocardiofacial syndrome (VCFS). DESIGN/SETTING: Retrospective review of all patients entered at one tertiary-level multidisciplinary cleft lip and palate and craniofacial anomalies panel from January 2000 to December 2003. PATIENTS: The study consisted of 115 patients. The presence or absence of the following clinical features was documented: cleft palate (submucous and overt), VPI, cardiac anomalies, renal anomalies, small stature, characteristic facies, developmental delay, psychiatric dysfunction, and family history. MAIN OUTCOME MEASURE: Correlation between presence or absence of clinical features of VCFS and presence or absence of 22q11.2 microdeletion by FISH analysis. RESULTS: Of the 16 patients (13.9%) who demonstrated 22q11.2 microdeletion by FISH analysis, 16 had VPI (100%), 16 had small stature (100%), 14 had cleft palate (88%), and 13 had characteristic facies (81%). Developmental delay was also present in 13 of these patients (81%), and seven had cardiac anomalies (44%). Multiple regression analysis revealed that the presence of characteristic facies and small stature statistically correlated with microdeletions of chromosome 22q11.2 by FISH studies (p < .05). CONCLUSIONS: Patients with microdeletions of chromosome 22q11.2 as demonstrated by FISH analysis were more likely to have VPI, small stature, cleft palate, characteristic facies, and developmental delay, in descending order. Statistical analysis showed that only characteristic facies and small stature correlated with 22q11.2 microdeletions.

Adolescent↗
PubMed2005

Mutation rates in the dystrophin gene: a hotspot of mutation at a CpG dinucleotide.

An analysis of mutations was performed in 141 Duchenne muscular dystrophy (DMD) patients previously found to be negative for large deletions by standard multiplex PCR assays. Comprehensive mutation scanning of all coding exons, adjacent intronic splice regions, and promoter sequences was performed by DOVAM-S, a robotically enhanced, high throughput method that detects essentially all point mutations. Samples negative for point mutations were further analyzed for duplications by multiplex amplifiable probe hybridization (MAPH). Presumptive causative mutations were detected in 90% of the patients (70% protein truncating point mutations, 13% duplications, and 7% deletions not detected by the standard multiplex screening method). A total of 40 of the mutations are putatively novel. Most duplications involve multiple exons with an average and median size of about 160 and 153 kb, respectively. This is the first analysis of the absolute and relative rates of point mutations in the dystrophin gene. Relative to microdeletions (0.68 x 10(-9) per bp per generation), transitions at CpG dinucleotides are enhanced 150-fold while complex indels, the least common mutation type, are less frequent than microdeletions by a factor of five. The frequency of microdeletions and microinsertions at mononucleotide repeats increases exponentially with length. When compared to the well-studied human factor IX gene (F9), the results are similar, with two exceptions: a hotspot of mutation in the dystrophin gene (c.8713C>T/p.R2905X) at a CpG dinucleotide and an altered size distribution of microdeletions. The hotspot reflects a difference in the underlying pattern of mutation, while the altered size distribution of microdeletions reflects certain abundant sequence motifs within the dystrophin coding sequence (relative to factor IX).

Adolescent↗
PubMed2007

Somatic microindels: analysis in mouse soma and comparison with the human germline.

Microindels, defined as mutations that result in a colocalized microinsertion and microdeletion with a net gain or loss of between 1 and 50 nucleotides, may be an important contributor to cancer. We report the first comprehensive analysis of somatic microindels. Our large database of mutations in the lacI transgene of Big Blue((R)) mice contains 0.5% microindels, 2.8% pure microinsertions, and 11.5% pure microdeletions. There appears to be no age, gender, or tissue-type specificity in the frequency of microindels. Of the independent somatic mutations that result in a net in-frame insertion or deletion, microindels are responsible for 13% of protein expansions and 6% of protein contractions. These in-frame microindels may play a crucial role in oncogenesis and evolution via "protein tinkering" (i.e., modest expansion or contraction of proteins). Four characteristics suggest that microindels are caused by unique mechanisms, not just simple combinations of the same mechanisms that cause pure microinsertions and pure microdeletions. First, microinsertions and microdeletions commonly occur at hotspots, but none of the 30 microindels are recurrent. Second, the sizes of the deletions and insertions in microindels are larger and more varied than in pure microdeletions and pure microinsertions. Third, microinsertions overwhelmingly repeat the adjacent base (97%) while the insertions in microindels do so only infrequently (17%). Fourth, analysis of the sequence contexts of microindels is consistent with unique mechanisms including recruitment of translesion DNA synthesis polymerases. The mouse somatic microindels have characteristics similar to those of human germline microindels, consistent with similar causative mechanisms in mouse and human, and in soma and germline.

Age Factors↗
PubMed2003

22q11 deletions in fetuses with malformations of the outflow tracts or interruption of the aortic arch: impact of additional ultrasound signs.

OBJECTIVES: One hundred and forty-one consecutive cases of malformations of the outflow tracts or interrupted aortic arch (IAA), detected by fetal echocardiography, underwent detailed anatomy scan, karyotyping and fluorescence in situ hybridization analysis (FISH) to detect the prevalence of 22q11 microdeletion and to evaluate neonatal clinical findings and outcome according to the presence of the genetic defect. Then, we sought to investigate whether some prenatal ultrasound findings could help identify fetuses at higher risk of carrying the 22q11 microdeletion. METHODS: Echocardiography and FISH for the DiGeorge critical region (22q11) were performed in all cases. RESULTS: 22q11 microdeletion was detected in 28 of 141 fetuses (19.8%). Intrauterine growth restriction (IUGR) appeared to be associated with the worst prognosis, being present in 2/2 intrauterine fetal deaths and 5/6 post-natal deaths. IUGR, additional aortic arch anomalies and thymic hypo/aplasia were significantly more frequent in fetuses with 22q11 microdeletion (p=0.011, 0.011 and <0.0001, respectively). Prenatal ultrasound thymus examination, performed on the last 84 fetuses, showed 75% sensitivity and 94% specificity. The combination of 2 predictors, namely, thymus defects and IUGR associated with additional aortic arch anomalies reached more than 90% sensitivity and 100% specificity. CONCLUSIONS: Our study demonstrates that 22q11 microdeletion occurs in 20% of malformations of the outflow tracts and IAA type B, as detected in utero, and that this association is significantly predicted by the presence of associated ultrasound findings: thymic hypo/aplasia, IUGR and additional aortic arch anomalies. The feasibility of a correct prenatal diagnosis should enable clinicians to provide the couple with further informative counselling and to plan adequate post-natal medical interventions.

Abnormalities, Multiple↗
PubMed1999

Transmission of de novo mutations of the deleted in azoospermia genes from a severely oligozoospermic male to a son via intracytoplasmic sperm injection.

OBJECTIVE: To investigate the transmission of microdeletions in the deleted in azoospermia (DAZ) genes to a male offspring via intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: Reproductive unit of a university teaching hospital. PATIENT(S): A 29-year-old, severely oligozoospermic male with microdeletions of the DAZ genes in Yq interval 6 and his son, who was conceived via ICSI. INTERVENTION(S): DNA screening for the microdeletions in Yq interval 6 with 24 sequence tagged sites with the use of polymerase chain reaction amplification for the patient, the patient's father, and the patient's son. Paternity identification was performed using nine hypervariable short tandem repeats. MAIN OUTCOME MEASURE(S): Deletion mapping of Yq interval 6 from sequence tagged sites and electropherogram of short tandem repeats for DNA fingerprinting. RESULT(S): The son had the same microdeletions of the DAZ genes as the patient, and the patient's father had normal DAZ genes. The paternity of the patient, the patient's father, and the patient's son was verified. CONCLUSION(S): De novo DAZ microdeletions in an infertile male can be transmitted to a male offspring via ICSI. DNA screening tests for DAZ genes before ICSI may help in the genetic counseling of patients with idiopathic azoospermia or severe oligozoospermia.

Adult↗
PubMed2005

[Study of AZF regions of Y chromosome in males with idiopathic infertility. Analysis of two methods of molecular diagnosis].

BACKGROUND AND OBJECTIVE: It is well known that both azoospermia and oligozoospermia are associated to microdeletions of single tagged sites (STS) in the long arm of the Y chromosome. Characterization of deletions is carried out by polymerase chain reaction, although the number and regions included in the analysis varies between laboratories. The aim of this study was to analyze the presence of chromosome Y microdeletions using 2 different sets of STSs. PATIENTS AND METHOD: We analysed the presence of microdeletions in the Yq chromosome in 30 patients with idiopathic male infertility, using 2 sets of STSs, those proposed by the European Molecular Genetics Quality Network (EMQN) as first choice and those of the Y Chromosome Deletion Detection System (Promega). RESULTS: AZF microdeletions were detected in 4 patients (13%). Only one case was detected simultaneously with both sets. CONCLUSION: In patients with idiopathic male infertility detection of AZF microdeletion in Y chromosome has important methodological problems. Further studies are needed to achieve a more reliable method to be used by clinical laboratories.

Chromosomes, Human, Y↗
PubMed2002

Genotyping of Israeli infertile men with idiopathic oligozoospermia.

Microdeletions of the long arm of the Y chromosome involving the azoospermia factor (AZF) region are associated with severe oligo- or azoospermia. Abnormal androgen receptor (AR) structure or function has also been implicated in male infertility. To assess the contribution of these genetic defects to male infertility, 61 Israeli men with severe oligo- (n = 15) or azoospermia (n = 46), were screened for Y chromosome microdeletions, and the AR-(CAG)n repeat length. Fifty fertile Israeli men were similarly analyzed. PCR amplification of 20-54 simple tag sequences (STSs) located at Yq was used to determine the rate and extent of Y chromosome microdeletions. PCR with primers flanking the AR-(CAG)n region and subsequent size fractionation on gradient acrylamide gels were used to determine AR-(CAG)n length. Five azoospermic individuals (5/61-8.2% and 5/46-10.8% of azoospermic patients) displayed Y chromosome microdeletions. The mean CAG repeat number in infertile men was 18.6 +/- 3.0 compared with 16.6 + 2.7 in fertile men (n = 50), a statistically significant difference (p = 0.003). Y chromosome microdeletions contribute to male infertility in our azoospermic population, and the mean length of the AR-CAG is significantly longer in our infertile population than in fertile men.

Adult↗