Cytogenetic and clinical features of a 13 year old male with trisomy 8.

Trisomy 8 is a relatively rare chromosomal abnormality. The majority of cases present with the mosaic form. Regular trisomy 8 is usually lethal and frequently results in miscarriage, while those with "trisomy 8 mosaicism" are more likely to survive. We report clinical observations and cytogenetic studies of a 13-year-old male with regular trisomy 8 and compared with those of other known cases of trisomy 8. The most discriminating findings for this condition are skeletal anomalies, restricted articular function, and speech problems. Our results are in agreement with those of previous studies for trisomy 8.

A case of complete tetraploidy in amniocentesis with normal karyotype in subsequent cordocentesis.

We report a case of complete tetraploidy in amniotic fluid culture obtained at 17 wk of pregnancy. Amniocentesis was performed in this pregnancy because of a high-risk maternal serum screening result and abnormal ultrasound findings. Amniotic fluid was cultured in two flasks. Growth was very slow in one culture with no growth in the other. Harvest was possible after 3 wk, which revealed tetraploidy in all studied plates. Subsequent cordocentesis was performed to confirm the diagnoses of amniocentesis. Chromosomal analysis of the cordocentesis revealed a normal karyotype with 46,XY. A healthy male infant was born at term. This case illustrates that abnormal karyotypes in poor growth cultures could be misleading and should be confirmed by another technique, such as cordocentesis.

Different chromosome Y abnormalities in a case with short stature.

We report a case with different chromosome Y abnormalities. Case was an 11-year-old boy, who was diagnosed with short stature, referred to laboratory of human medical genetics laboratory for genetic evaluation. Chromosomal analysis of the case was carried out on peripheral blood lymphocyte culture. Classic cytogenetic analysis (G and C banding) was confirmed by using fluorescence in situ hybridization analysis (FISH) technique. Cytogenetic and FISH analysis showed a mosaic 46,X,i(Yq)/45,X/47,X,i(Yq)x2/47,XYY karyotype. Case, which was found interesting due to its rarity, is discussed with its clinical features and cytogenetic results, in the light of relevant source information. This case underlines the importance of karyotyping patients with unexplained short stature. This clinical report also will be helpful in defining the phenotypic range associated with these karyotypes.

FSHR single nucleotide polymorphism frequencies in proven fathers and infertile men in Southeast Turkey.

The influence of FSH receptor (FSHR) variants on male infertility is not completely understood. The present investigation is the first screening study for SNP at nucleotide position -29 in the core promoter region and codon 680 in exon 10 of the FSHR and the effect of the serum levels of FSH on male infertility in Southeast Turkey. The SNPs in codon 680 and at position -29 of the FSHR gene were analyzed by PCR-RFLP technique in 240 men with proven fathers, and 270 infertile men (150 nonobstructive azoospermic and 120 severe oligozoospermic). The separate analysis for SNP at nucleotide position -29 did not show any difference in genotypic frequencies and serum FSH levels. The genotype distribution of SNP at position 680 was different but does not influence serum FSH levels. Together the two SNPs form four discrete haplotypes (A-Thr-Asn, G-Thr-Asn, A-Ala-Ser, and G-Ala-Ser) occurring in 10 combinations. A statistically significant difference in the allelic distribution of G-Asn/G-Ser and G-Ser/G-Ser genotype between proven fathers and infertile men but there were not any statistically significant difference in the overall frequency of the four FSHR haplotypes. We conclude that the FSHR haplotype does not associate with different serum FSH levels but it is differently distributed in proven fathers and infertile men.

Parental decisions regarding a prenatally detected fetal chromosomal abnormality and the impact of genetic counseling: an analysis of 38 cases with aneuploidy in Southeast Turkey.

This study investigated parental decision-making to terminate or continue a pregnancy after prenatal diagnosis of a chromosomal abnormality among a sample of patients in Southeast Turkey. Between 2004 and 2007, 1068 amniocentesis tests were performed in the Medical Biology and Genetic Department Laboratory at Dicle University. Aneuploidy was found in 38 cases (3.56%). Genetic counseling was provided for the couples that received abnormal results, and they were later interviewed and asked if they had continued or interrupted the pregnancy after the diagnosis. When confronted with autosomal aneuploidy in which a severe prognosis was expected, 85% of cases decided to terminate the pregnancy. When confronted with sex chromosome aneuploidy with a low risk of an abnormal clinical phenotype 60% of cases decided to continue the pregnancy. Among the diagnoses with aneuploidy, pregnancy was continued in 21.1% of cases due to religious beliefs regardless of whether there was a low or severe risk of an abnormal clinical phenotype. These findings indicate that both severity of abnormality and religiosity play an important role in genetic counseling patients' decision-making processes and outcomes in Turkey. In addition, the findings suggest the need for legislation that reduces the differences in approaches between the physicians and institutions regarding parental decision-making to terminate or continue a pregnancy in our country.

Cytogenetic and clinical studies of a male infant with disorder of sexual development: case report.

OBJECTIVE: To report a translocation between chromosomes 3 and 4: 46,XY,t(3;4)(p25;q31.3) in a male infant with a disorder of sexual development. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 1-year-old infant who presented with abnormal location of the urethral meatus. INTERVENTION(S): Cytogenetic analysis, fluorescence in situ hybridization (FISH), and serum concentrations measurement (using peripheral blood), and clinical examination. MAIN OUTCOME MEASURE(S): Karyotype and clinical findings. RESULT(S): On clinical examination, bilateral testicular volume and phallus were determined to be undersized. Serum concentrations of T and DHEAS were low. G-banding of his chromosomes showed that the patient had a balanced translocation involving chromosomes 3 and 4: 46,XY,t(3;4)(p25;q31.3). This karyotype finding was confirmed by FISH. The FISH analysis revealed the presence of sex-determining region (SRY). The proband inherited this translocation from his father. His sister had the same translocation. However, the father and sister of the proband were clinically normal. CONCLUSION(S): The presence of this chromosomal anomaly and hypospadias was unique to our patient compared with others with the 46,XY,t(3;4) translocation. Although no such association has been reported to date, we think that the severe hypospadias in our case might be associated with this translocation.

Polymorphisms of the angiotensin converting enzyme and angiotensin II type 1 receptor genes and renal scarring in non-uropathic children with recurrent urinary tract infection.

AIM: The aim of this study was to investigate whether the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (A1166C) gene polymorphisms were associated with the renal scar formation secondary to recurrent urinary tract infection in children without uropathy. METHODS: The polymorphisms were investigated by polymerase chain reaction in 97 children (81 females, 16 males; age, 2.5-13 years) with recurrent urinary tract infection and 100 healthy controls as a single centre study. Children with vesicoureteral reflux, bladder dysfunction and other uropathies were excluded. The dimercaptosuccinic acid (DMSA) scan performed at least 3 months after a proven urinary tract infection and the result of the last DMSA was taken into consideration. RESULTS: Renal scarring was found in 30 patients (30.9%) using DMSA scan. The number of urinary tract infection attacks was significantly higher in patients with renal scarring compared with children without scarring (P<0.05). The follow-up period and male/female ratio of patients with or without renal scarring was similar (P>0.05). Age at the first urinary tract infection was lower in the group with scarring. The ACE insertion/deletion genotype distribution and D allele frequency were similar between patients and controls (P>0.05), and in patients with renal scarring and those without renal scarring. Also, the angiotensin II type 1 receptor gene polymorphism was not associated with renal parenchymal damage (P>0.05). CONCLUSION: The results indicated that the ACE insertion/deletion and angiotensin II type 1 receptor gene polymorphisms were not independent risk factors for renal scar formation in recurrent urinary tract infection of paediatric patients without uropathy.

Determination of serum hepatitis B virus DNA in chronic HBsAg carriers: clinical significance and correlation with serological markers.

BACKGROUND/AIMS: Hepatitis B virus infection is among the most devastating health problems in the world, including Turkey. In this cross-sectional study, we aimed to investigate the correlations between hepatitis B virus genomic load and various measures of the progression of chronic hepatitis B virus infection. METHODS: A total of 354 chronic HBsAg carriers [126 inactive HBsAg carriers, 50 asymptomatic replicative carriers (immune tolerant patients), 90 chronic hepatitis B patients and 88 patients with liver cirrhosis] were enrolled into the study. Eligible patients included males and females, 14-62 years of age, with detectable serum HBsAg, HBeAg or anti-HBe in serum at the time of screening and for at least six months before study entry. Serum hepatitis B virus DNA was detected by liquid hybridization, and results under the level of 1 pg/ml were additionally confirmed by polymerase chain reaction. RESULTS: Of 354 patients, 118 (33%) were HBeAg-positive and 236 (67%) HBeAg-negative. Of HBeAg-negative patients, 126 (53%) had normal alanine aminotransferase, 31 (13%) had elevated alanine aminotransferase (chronic hepatitis B) and 79 (33%) had evidence of cirrhosis; corresponding figures in the HBeAg-positive patients were 50 (42%), 59 (50%) and 9 (8%). There is a significant correlation between transaminase values and histological liver damage, whereas no correlation was found between viral replication and liver damage. CONCLUSIONS: Hepatitis B virus DNA is an important and specific marker for ongoing hepatitis B virus related liver disease, but alanine aninotransferase was shown to be the best marker for liver inflammation and not hepatitis B virus viral load. Although these findings are not new, they are of some utility since they prevent unnecessary and cost-intensive viral load determinations in chronic HBsAg carriers.

The lack of effect of therapeutic vaccination with a pre-S2/S HBV vaccine in the immune tolerant phase of chronic HBV infection.

BACKGROUND/AIMS: Even if the results are controversial and preliminary, several reports suggest that the HBV vaccine might be effective in treating HBV infection. In this study, we aimed to evaluate the efficacy and safety of specific anti-HBV vaccination for the immune tolerance phase of chronic HBV infection in a randomized, controlled study. PATIENTS AND METHODS: The 47 subjects included patients that were treatment-naive with hepatitis B e antigen positivity, active hepatitis B virus replication as measured by hepatitis B virus DNA levels, persistently normal alanine transaminase levels, and with minimal or absent disease activity by liver biopsy. Thirty patients were given three intramuscular injections of 20 micro g of a pre-S2/S vaccine (GenHevac-B) on days 0, 30, and 60, and the remaining 17 patients were included in the control group. The efficacy of vaccination was evaluated by testing for loss of serum HBV DNA or decrease in its level and for HBeAg seroconversion. A significant decrease in HBV DNA levels was accepted as a decrease of >50% of initial values. The complete response was defined as loss of HBV DNA in serum with HBeAg seroconversion. Postvaccination follow-up lasted 12 months after the first dose. RESULTS: No significant effects were observed in the vaccination population in the reduction of HBV DNA to undetectable levels, or to <50% of prevaccination levels, in HBeAg/anti-HBe seroconversion, or in transaminase levels. There was an early clearance/decrease in HBV DNA levels in five vaccinated patients by 3 months, and none in controls (P = 0.143), and two of them had sustained responses later. At the end of follow-up, complete response is almost similar in study as well as control group (13% vs. 12%, P > 0.05). Disappearance of serum HBV DNA was more frequently observed in those patients who had pretreatment viremia of <100 pg/mL in both groups. The median levels of HBV DNA and alanine transaminase activity between baseline and 12 months did not differ significantly in both groups. All patients remained HBsAg positive and none developed anti-HBs. No serious adverse event was encountered in vaccinated patients, and the therapy was well tolerated. Follow-up lasted a median of 16 months (range 12-30 months) for the study group and 18 months (range 12-31months) for the control group. CONCLUSIONS: Immunotherapy with specific anti-HBV vaccine in the immune tolerance phase of chronic HBV infection did not offer additional benefit. New immunotherapeutic strategies to control HBV infection by specific HBV vaccines in chronically infected subjects are needed.

Hypomelanosis of ito with trisomy 13 mosaicism [46, XY, der (13;13) (q10;q10), +13/46,xy].

The term hypomelanosis of Ito (HI) has been used as a diagnosis for individuals with swirly hypopigmentation or depigmentation distributed along the lines of Blaschko. HI should be appropriately evaluated for a possible association with chromosomal or genetic mosaicism or chimerism. We report a six-month-old severely motor and mental retarded boy with these typical cutaneous lesions associated with extracutaneous features, including facial dysmorphism, polydactyly, and inguinal hernia. The cytogenetic examination of lymphocytes demonstrated a mosaicism of 46, XY, der (13;13) (q10;q10), +13/46, XY. This is the first case reported in the literature showing an association between phylloid pigmentary pattern of hypomelanosis of Ito and trisomy 13 mosaicism.