MULTIPLE CONGENITAL ANOMALIES IN A CHILD WITH 47,XY,+der(8;9)(p10;p10): A CASE REPORT.

Complex small supernumerary marker chromosomes (sSMC) constitute one of the smallest subgroups of sSMC in general. Complex sSMC consist of chromosomal material derived from more than one chromosome. We report a complex sSMC derived from chromosomes 9 and 8, characterized as der(8;9)(p10;p10) resulting from unbalanced transition of maternal balanced translocation. Besides dysmorphic face and mental-motor retardation, the patient had Dandy-Walker malformation (DWM) in cranial MR also. As far as we are concerned, this is the first complex sSMC case comprising short arms of 8th and 9th chromosomes.

A NOVEL MUTATION IN NPR2 GENE IN A PATIENT WITH ACROMESOMELIC DYSPLASIA, MAROTEAUX TYPE.

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare autosomal recessive disease characterized by disproportionate shortening of skeletal elements, predominantly affecting the middle segments (forearms and forelegs) and distal segments (hands and feet) of appendicular skeleton. Furthermore it is related to axial skeleton and leads to wedging of vertebral bodies, with shorter dorsal margins than the ventral margins. Bartels et al. defined mutations in NPR2 gene, encoding natriuretic peptide receptor B (NPR-B), underlying Acromesomelic dysplasia, type Maroteaux. We present here molecular and clinical findings of a case with AMDM. In a patient, a novel homozygous mutation c.1435C>T p.R479X in exon 7 of NPR2 gene was found. Further testing confirmed the heterozygous carrier status of the parents. Our findings expand the spectrum of causative mutations in AMDM.

A novel mutation in the FRAS1 gene in a patient with Fraser syndrome.

Fraser Syndrome (FS) is a rare disease with autosomal recessive inheritance characterized by cryptophthalmus, cutaneous syndactyly, laryngeal and urogenital anomalies. Mutations in the genes FRAS1 and FREM2 encoding components of a protein complex of the extracellular matrix, and recently also mutations in GRIP1 have been found to be causative for FS. We present here molecular and clinical findings of a patient with FS who was found to have a novel homozygous frameshift mutation c.9739delA, p.(T3247Pfs*44) in exon 63 of FRAS1 gene. Further testing confirmed the heterozygous carrier status of parents.

A fertile patient with 45X/47XXX mosaicism.

Turner syndrome (TS) is a sex chromosome abnormality with a frequency of 1/2,000-3,000 among female live births. Characteristic findings are short stature and gonadal dysgenesis. Short and webbed neck, low posterior hairline, broad chest, widespread nipples, cubitus valgus, short 4th and 5th metacarpals, multiple pigmented nevi, primary amenorrhea, lack of secondary sexual characteristics, cardiovascular and renal anomalies are the most common presentations. Most of the cases are infertile. Spontaneous pregnancy is unusual and the risk for congenital anomaly, spontaneous abortion, stillbirth and aneuploidy is increased. Fifty percent of the patients have classical monosomy X (45,X). However mosaicism of 45,X/47,XXX is rare and accounts for 1.7% of the TS cases. Some cases may not reflect the characteristic phenotype. Some cases with normal height, normal menstrual cyclus and fertility have been defined before. The case we present herein is a 26 years old woman who was admitted to our clinic due to recurrent pregnancy loss. In her medical history she had type 1 diabetes mellitus and endometrium cancer, in her family history her mother had recurrent pregnancy loss. The patient's first, third, fourth, fifth and sixth pregnancies had resulted in spontaneous abortions in the first trimester. She had a healthy daughter with 46,XX karyotype from her second pregnancy. A 45,X[8]/47,XXX[12] karyotype was detected by conventional cytogenetic analysis of the patient who did not have dysmorphic findings. The mosaicism was confirmed by FISH analysis with CEP X probe. Of the 100 cells evaluated, 65 of them had 3 signals of X chromosome while 35 had 1 signal. We present the case because of its scarcity in the literature.

De novo partial trisomy distal 4q: a case report.

We present a case of de novo distal partial trisomy 4q with firstly described chronic cholecystitis, rarely seen hypothyroidism, and bilateral membranous choanal atresia. The patient, a 10-month-old baby girl had dysmorphic facial features as well as neuromotor retardation, congenital hypothyroidism, atrial septal defect (ASD), white matter atrophy in cranial MRI, grade 2 dilatation in pelvicalyceal system of the left kidney, and bilateral ureteral reflux. In peripheral blood chromosome analysis 46, XX, dup(4) (q21q35) karyotype was detected. In FISH analysis using 4p/4q subtelomeric probe; 3 signals for 4 q region and 2 signals for 4p region were observed. In chromosome analyses of her healthy parents, no anomaly was detected. Herein we present a case of de novo partial distal trisomy 4q syndrome to contribute to the literature since it is rarely seen and this is the first patient with partial trisomy distal 4q syndrome presented with chronic cholecystitis and the second patient with hypothyroidism.

Another small supernumerary marker chromosome derived from chromosome 9 in a Klinefelter patient / Otro cromosoma marcador supernumerario pequeño derivado del cromosoma 9 en un paciente con el síndrome de Klinefelter

Marker chromosomes are very rare in Klinefelter patients and phenotypic findings are related to the affected chromosomal region. The phenotypic effects of small supernumerary marker chromosomes (sSMC) range from multiple malformations/mental retardation to no effect (ie a normal phenotype). This wide spectrum of phenotypes is due to the origin, structure and gene content of the marker chromosome. The first Klinefelter case with sSMC 9 was published by Liehr et al in 2005. The present case was referred for chromosomal analysis because of dysmorphic features, speech delay and mild mental retardation. Conventional cytogenetic analysis revealed the 47 XXY karyotype in 17 metaphases and the 48 XXY + marker karyotype in eight metaphases. Fluorescence in situ hybridization (FISH) analysis to identify the marker chromosome was performed using the LSI p16 (9p21) Spectrum Orange/CEP 9 SpectrumGreen Probe (Vysis CDKN2A/CEP 9 FISH Probe) and partial trisomy 9 mosaicism was confirmed in this patient. To our knowledge, this is the second case of Klinefelter syndrome with a small supernumerary marker chromosome derived from chromosome 9.

Los cromosomas marcadores son muy raros en los pacientes de Klinefelter, y los hallazgos fenotípicos se relacionan con la región cromosomática afectada. Los efectos fenotípicos de los cromosomas marcadores supernumerarios pequeños (sSMC) van desde el retraso mental y las malformaciones múltiples hasta la ausencia total de efectos (es decir, un fenotipo normal). Este amplio espectro de fenotipos se debe al origen, estructura y contenido del gen del cromosoma marcador. El primer caso de síntoma Klinefelter con sSMC 9 fue publicado por Liehr et al en 2005. El caso presente fue remitido para análisis cromosomático debido a rasgos dismórficos, retraso del habla, y retardo mental ligero. El análisis citogenético convencional reveló el cariotipo 47 XXY en 17 metafases y el cariotipo marcador 48 XXY+ en ocho metafases. El análisis mediante hibridación fluorescente in situ (FISH) para identificar el cromosoma marcador se realizó usando la sonda LSI p16 (9p21) Spectrum Orange/CEP 9 SpectrumGreen Probe (Vysis CDKN2A/CEP 9 FISH Probe). Un mosaicismo de trisomía 9 parcial fue confirmado en este paciente. Hasta donde sabemos, éste es el segundo caso de síndrome de Klinefelter con un cromosoma marcador supernumerario pequeño derivado del cromosoma 9.

The variant translocation of ABL1 gene t(2;9)(q21;q34) in a childhood T-cell acute lymphoblastic leukemia.

We present the case of the childhood ALL that was identified by the translocation of the ABL1 gene to the q21 band of chromosome 2 without t(9;22)(q34;q11) translocation. The observation of a poor clinical course of the case may contribute to explanation of the action of t(9;22)(q34;q11) translocation, of which poor prognostic action is known on ALL's, in terms of ABL1 gene, independent of the BCR gene. On the other hand, the prognostic significance of this variant ABL1 translocation detection, which is very rarely observed, will cast a light on future cases (Tab. 1, Fig. 1, Ref. 11).

Another small supernumerary marker chromosome derived from chromosome 9 in a Klinefelter patient.

Marker chromosomes are very rare in Klinefelter patients and phenotypic findings are related to the affected chromosomal region. The phenotypic effects of small supernumerary marker chromosomes (sSMC) range from multiple malformations/mental retardation to no effect (ie a normal phenotype). This wide spectrum of phenotypes is due to the origin, structure and gene content of the marker chromosome. The first Klinefelter case with sSMC 9 was published by Liehr et al in 2005. The present case was referred for chromosomal analysis because of dysmorphic features, speech delay and mild mental retardation. Conventional cytogenetic analysis revealed the 47XXY karyotype in 17 metaphases and the 48 XXY + marker karyotype in eight metaphases. Fluorescence in situ hybridization (FISH) analysis to identify the marker chromosome was performed using the LSI p16 (9p21) Spectrum Orange/CEP 9 SpectrumGreen Probe (Vysis CDKN2A/CEP 9 FISH Probe) and partial trisomy 9 mosaicism was confirmed in this patient. To our knowledge, this is the second case of Klinefelter syndrome with a small supernumerary marker chromosome derived from chromosome 9.

Investigation of ABCB1 gene polymorphism with colchicine response in Behçet's disease.

Colchicine is commonly used in the treatment of Behçet's disease. However, some patients are unresponsive to colchicine treatment. Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transports colchicine out of cells. We investigated a possible association of C3435T polymorphism of the ABCB1 (MDR1) gene with colchicine response in patients with Behçet's disease. We randomly selected 97 patients with Behçet's disease, examined ABCB1 (MDR1) gene C3435T polymorphisms, and evaluated patient responses to colchicine. Forty-three patients were colchicine responsive, while the remaining 54 patients were unresponsive. No significant difference was found between genotypic and allelic frequencies of the ABCB1 C3435T polymorphisms in patients with Behçet's disease and healthy volunteers. Also, there was no significant difference among responsive and nonresponsive patients. We concluded that ABCB1 C3435T polymorphism is not associated with a colchicine response in patients with Behçet's disease.

Lack of association of ACE gene I/D polymorphism with obstructive sleep apnea syndrome in Turkish patients.

Angiotensin-converting enzyme (ACE) is a vital enzyme in the renin-angiotensin-aldosterone system, and there are reports in the literature describing its role in the development of cardiovascular system diseases, with I/D polymorphism of the ACE gene. We examined the relationship between a patient group with obstructive sleep apnea syndrome (OSAS) and a control group in terms of I/D polymorphism of the ACE gene. We examined 64 patients, with 37 individuals serving as the control group. PCR was used to detect ACE I/D gene polymorphism. Genotype was determined according to the bands that formed on agarose gel electrophoresis. Among the 64 OSAS patients, 27 were identified with the ID genotype, 27 with the DD genotype and 10 with the II genotype; among the 37 control subjects, 19 were identified with the ID genotype, 11 with the DD genotype and 7 with the II genotype. When the case group and controls were compared in terms of ID, II and DD genotypes, no significant difference was observed. On the other hand, when the two groups were compared with respect to mean body mass index, the OSAS group was found to be significantly different from the control group (P = 0.009). We conclude that ACE I/D gene polymorphism is not a genetic risk factor for OSAS in Turkish patients.

Extended pedigree with multiple cases of XX sex reversal in the absence of SRY and of a mutation at the SOX9 locus.

It is well established that testicular differentiation of the human embryonic gonad depends on the action of the Y-chromosomal gene SRY. However, exceptional cases such as SRY-negative cases of 46,XX testicular disorder of sexual development (DSD), and of 46,XX ovotesticular DSD document that testicular tissue can develop in the absence of the SRY gene. These SRY-negative XX sex reversal cases are very rare and usually sporadic, but a few familial cases have been reported. We present a large, consanguineous family with nine affected individuals with phenotypes ranging from 46,XX testicular DSD to 46,XX ovotesticular DSD, with predominance of male characteristics. Absence of SRY in peripheral blood was documented by fluorescence in situ hybridization (FISH) and PCR analysis in all nine affected individuals, and by FISH analysis on gonadal sections with testicular tissue in four affected individuals. By quantitative PCR, a duplication of the SOX9 gene was excluded. In addition, as linkage analysis showed that the nine affected members of the family do not share a common SOX9 haplotype, any mutation at the SOX9 locus could be ruled out. Together, these findings implicate a mutation at a sex-determining locus other than SRY and SOX9 as the cause for the XX sex reversal trait in this family.

Effects of seasonal and physiological variations on the serum chemistry, vitamins and thyroid hormone concentrations in sheep.

The aim of this study was to investigate the possible effects of the reproductive status and seasonal variations on the serum chemistry and vitamin status and their relationships with the thyroid hormones in Sakiz-Awassi crossbreed sheep. The sheep (n = 34) were divided into two groups. The first group (n = 22) was mated; the second group (n = 12) was not mated. Their serum samples were collected four times a year at the each season and under reproductive status. The periods are 1, early pregnancy (October); 2, late pregnancy (January); 3, lactation (April); and 4, dry season (July). The results of this study indicated that (1) total protein (TP), globulin, cholesterol, creatinine, uric acid and T4/T3 vary with reproductive status but not seasonal variations; (2) alanine aminotransferase, T4, fT4 concentrations in serum vary only with reproductive status; (3) the urea, creatine kinase, lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, amylase, albumin, triglyceride, VLDL, Vit A-E, T3 and fT3 concentration could vary with both reproductive status and seasonal variations; (4) the glucose, gamma-glutamyl transpeptidase, folate concentrations were altered neither season of the year nor the reproductive status; (5) a single reference interval for folate, gamma-glutamyl transpeptidase (GGT), glucose, TP, globulin, cholesterol, creatinine, uric acid and T4/T3 can be used for both mated and non-mated sheep because of no differences were found due to the reproductive status. Taking the results together suggests that reproductive status and seasonal variations have to be taken into consideration for a correct interpretation of the serum chemistry values of sheep. Nutritional supplements are required for sheep during certain periods to avoid a decline of their performance, which would then represent consequent economic, loses.

The role of triple therapy, age, gender and smoking on the genotoxic effects of Helicobacter pylori infection.

The role of age, gender and smoking on both the genotoxic effects of Helicobacter pylori and the efficacy of eradication therapy in a group of patients with gastritis was investigated. Gastritis was confirmed by endoscopy and biopsy, and the presence of H. pylori by urease testing. Pre- and post-treatment peripheral blood lymphocyte cultures were prepared from 17 patients and 25 metaphases per patients were analysed for sister chromatid exchange (SCE), a well-established technique for the evaluation of human exposure to toxic agents. Treatment with omeprazole, clarithromycin and amoxycillin triple therapy eradicated H. pylori in 94% of patients and significantly reduced the SCE frequency. Pre-treatment SCE frequency was found to be positively correlated with age. Female smokers tended to have higher post-treatment SCE frequencies than male smokers, and pre- and post-treatment SCE frequencies were higher in older males than in older females. Eradication therapy decreased the genotoxicity of H. pylori, but age in males and smoking in females may decrease treatment efficacy.