Gülsen Ökten

A 19-year follow-up of a patient with type 3 ectrodactyly-ectodermal dysplasia-clefting syndrome who developed non-Hodgkin lymphoma.

The ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome is characterized by ectrodactyly, ectodermal dysplasia, and clefting. The development of a malignancy with EEC syndrome is very rare. Here we present follow-up on a Turkish boy with EEC syndrome type 3 who developed malignant lymphoma with high expression of p63. He had chronic renal failure due to recurrent urinary infections caused by ureterovesical reflux. Cervical, diffuse, large, B-cell non-Hodgkin lymphoma with high expression of p63 was diagnosed, and the patient died at 19 years of age. The transcription factor p63 is a key regulator of ectodermal, orofacial, and limb development. Mutations in the p63 gene can cause syndromes of ectodermal dysplasia, ectrodactyly, and orofacial clefting. Malignant lymphoma is a very rare complication of EEC syndrome. We suggest that p63 gene mutation analysis should be performed in every EEC syndrome patient with the possibility of developing malignant tumors.

The Mayer-Rokitansky-Kuster-Hauser and gonadal dysgenesis anomaly in a girl with 45,X/46,X,del(X)(p11.21).

The Mayer–Rokitansky–Kuster–Hauser (MRKH) anomaly is characterized by uterine aplasia or hypoplasia associated with normal ovaries [Morcel et al., 2007]. The co-occurrence of gonadal dysgenesis and mullerian agenesis has been previously described as a rare event [Alper et al., 1985; Mohapatra et al., 1992; Guitron-Cantu et al., 1999]. Structural or numerical abnormalities of X chromosome can cause gonadal dysgenesis as absent or streak gonads [Goldman et al., 1982]. Although gonadal dysgenesis has been reported with structural abnormalities in X chromosome such as 46Xi(Xq),45,X and 45X/46XX, neither structural nor numerical abnormalities of X chromosome have been associated with the MRKH anomaly [Gardo et al., 1971; De Leon et al., 1984; Gray et al., 2001]. Associated skeletal abnormalities including spine, face and limb such as asymmetric or fused vertebra, ectrodactly, radial agenesis and facial asymmetry have been reported in patients with MRKH [Behera et al., 2005; Morcel et al., 2007]. The etiology of this condition is still unknown. Here, we report on a girl whohas 45,X/46,X,del(X)(p11.21!pter)withMRKH and gonadal dysgenesis. A 17-year-old girl with complaints short stature, primary amenorrhea, hypertrophy of both second toes was admitted to the hospital. She was attending high school, and her school performance was good. She had two sisters and two brothers who were chromosomal and physically normal. There was no consanguinity in her parents who were also normal. Physical examination showed that her height was 129.9 cm (<3rd centile); weight 28.8 kg (<3rd centile). Height SDS was – 4.5, bone age was 12. She had downslanting palpebral features, a webbed neck, low posterior hairline, cubitus valgus, and short 4th metacarpals. She also had long and hyperplastic second toes in both feet (Fig. 1) and a grade 1/6 systolic murmur. Development of breast was Tanner phase I, pubic hair Tanner phase II. Axillary hair was absent. Serum gonadotropin levels were high (LH: 14.43 ml U/ml, FSH: 86.59 ml U/ml) and estradiol level were low (10.44 pg/ml). Thyroid function test was normal. Serum fasting glucose, lipids and insulin levels were within normal range. Bone mineral density (BMD) obtained from lumbar vertebral and femoral neck was osteopenic (Z score: 1.93 and 1.21, respectively). Echocardiographic and abdominal ultrasonographic examinations were normal. Ultrasonographic examination and magnetic resonance imaging of the pelvis revealed absence of uterus and ovaries and hypoplastic vagina. Cytogenetic analysis was performed on peripheral blood lymphocytes. A 100 GTG banded metaphases were analyzed utilizing the following DNA probe sequences: CEP X (DXZ1) SpectrumAquaTM; TelVysion Xp/Yp SpectrumGreenTM TelVysion Xq/Yq SpectrumOrangeTM (Vysis). Of 100 metaphase cells examined from PHA-stimulated blood cultures by conventional G-banding techniques, 30 were characterized as missing a sex chromosome (45,X) while the remaining 70 were characterized as containing number of chromosomes with deletion

Two Males with SRY-Positive 46,XX Testicular Disorder of Sex Development

The 46,XX testicular disorder of sex development (46,XX testicular DSD) is a rare phenotype associated with disorder of the sex chromosomes. We describe the clinical, molecular, and cytogenetic findings of a 16- and a 30-year-old male patient with sex-determining region Y (SRY)-positive 46,XX testicular DSD. Chromosomal analysis revealed 46,XX karyotype. Fluorescence in situ hybridization (FISH) showed the SRY region translocated to the short arm of the X chromosome. The presence of the SRY gene was also confirmed by polymerase chain reaction (PCR). The X chromosome inactivation (XCI) assay showed that both patients have a random pattern of X chromosome inactivation. This report compares the symptoms and features of the SRY-positive 46,XX testicular DSD patients.

An epileptic case with mosaic ring chromosome 6 and 6q terminal deletion

Ring chromosomes are rare chromosome disorders that arise usually de novo. Children with ring chromosome 6 have a wide range of intellectual functioning and congenital anomalies. We report an epileptic case of a 10-year-old boy to be mild psychomotor retardation and dysmorphic traits including microcephaly, brachycephaly, flat occiput, large and apparently low set ears, and bilateral syndactyly between his second and third fingers with mosaic ring chromosome 6 and 6q terminal deletion. Peripheral chromosome and fluorescent in situ hybridisation (FISH) analysis of the patient showed mos46,XY,r(6)(p24;q26),del(6)(q27) [30]/46,XY,del(6)(q27) [20] de novo. We presented the patient in the light of literature because the mosaic ring 6 and 6q terminal deletion was different caryotypically from other mosaic ring 6 patients.

Disruption of HDX gene in premature ovarian failure.

We present a case of a 19-year-old phenotypically normal girl with premature ovarian failure. Cytogenetic analysis using G banding and fluorescence in situ hybridization (FISH) from cultured peripheral blood lymphocytes of the patient and the family revealed a de novo X;15 translocation and the imbalance to be 46,X,t(X;15)(Xpter → Xq21::15q11 → 15qter;15pter → 15q11::Xq21 → Xqter). ish (CEPX+, wep15+, ISNRPN+, PML+, D15S10+, wcp15-, SNRRN-, PML-)[20]. The X chromosome inactivation (XCI) assay revealed a completely skewed XCI pattern in which selective pressure favors an active maternal allele. The Affymetrix 2.7 M cytogenetics whole-Genome array confirmed the chromosomal imbalance and identified disruption of the HDX gene at Xq21, the translocation breakpoint.

Impressions from the International Stem Cell Symposium

The importance of endogenous stem cells in homeostasis and repair of various tissues is well recognized. However, their use as therapeutic tools in most potential regenerative medicine applications is still at an early stage. The first International Stem Cell Conference was organized by Ondokus Mayis University in Samsun, Turkey to bring Turkish and international researchers together to discuss recent developments, ongoing challenges, and potential solutions. The meeting engaged not only established investigators but many trainees in diverse aspects of stem cell biology and regenerative medicine. The enthusiasm expressed and multidisciplinary approaches described bode well for the future of basic science and translational medicine.