Familial Atypical Hemolytic Uremic Syndrome with Positive p.S1191L (c.3572C>T) Mutation on the CFH Gene: A Single-center Experience.

The atypical hemolytic uremic syndrome (aHUS) is characterized by thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI), which can exhibit a poor prognosis. Complement factor H (CFH) gene mutations play a key role in this disease, which may be sporadic or familial. We studied 13 people from the same family, investigated for gene mutations of the familial aHUS after a family member presented to our emergency clinic with the aHUS and reported a family history of chronic renal failure. The p.S1191L mutation on the CFH gene was heterozygous in six people from the patient's family with the aHUS. One of these family members is our patient with acute kidney injury, and the other two are followed at the Nephrology Clinic, Medeniyat University, Goztepe Training and Research Hospital, Istanbul, Turkey, due to chronic renal failure. The other three family members showed no evidence of renal failure. The index case had a history of six sibling deaths; three died of chronic renal failure. Plasmapheresis and fresh frozen plasma treatment were administered to our patient. When the patient showed no response to this treatment, eculizumab (ECZ) therapy was started. The study demonstrated that thorough family history should be taken in patients with the aHUS. These patients may have the familial type of the disease, and they should be screened genetically. Eculizumab should be the first choice in the treatment with plasmapheresis. It should be kept in mind that the use of ECZ as prophylaxis in posttransplant therapy is extremely important for preventing rejection.

A CASE OF SOTOS SYNDROME CAUSED BY A NOVEL VARIANT IN THE NSD1 GENE: A PROPOSED RATIONALE TO TREAT ACCOMPANYING PRECOCIOUS PUBERTY.

Sotos syndrome is characterized by overgrowth, macrocephaly, distinctive facial features, and learning disabilities and is associated with alterations in the nuclear receptor binding SET domain protein 1 (NSD1) gene. Due to the advanced bone age, the eventual adult height is usually at the upper limit of normal. In this case report, a 6-year and 10-month old boy who presented with Sotos syndrome was described. He also had increased testicular volumes with advanced bone age. The stimulated levels of gonadotropins revealed central precocious puberty and brain magnetic resonance imaging (MRI) showed a pineal cyst. A heterozygous duplication variant [NM_022455.4:c.4560dup; p.(His1521Thrfs*9)] in the NSD1 was identified. Triptorelin acetate treatment was started. The aim was to report the novel duplication variant in the NSD-1 in a patient with Sotos syndrome accompanied by a pineal cyst and central precocious puberty, and also to discuss the rationale for treating precocious puberty.

TWO DIFFERENT MUTATIONS OF GL13 GENE IN TWO DIFFERENT SYNDROMES.

Polydactyly is among comnion extremity abnormalities. Mutations of GLI3 gene have been reported commonly in Greig Cephalopolysyndactyly Syndrome (GCPS) and Pallister-Hall Syndrome (PHS). We have determined two different mutations of GLI3 gene in two different cases, one of which is with GCPS and the other one is with PHS. A deletion mutation was detected in the proband with GCPS and his mother. Otherwise, we found that, unlike the previously reported, the mutation c.2437C>T, p.Q813X which was detected in the GLI3 gene caused typical PHS. We are in thought of that our cases will contribute to understanding of phenotypic variability leading to GLI3 mutations.

Prevalence of X-aneuploidies, X-structural abnormalities and 46,XY sex reversal in Turkish women with primary amenorrhea or premature ovarian insufficiency.

Our objective was to identify the distribution of cytogenetic abnormalities of 175 Turkish women with primary amenorrhea (PA) or premature ovarian insufficiency (POI). A retrospective study was performed using medical records of 94 patients with PA and 81 patients with POI at the Genetics Department, Zeynep Kamil Women's and Children's Research and Training Hospital, Istanbul, Turkey. G-banded metaphase karyotype analysis were prepared and analyzed. Chromosomal abnormalities were present in 44 of 175 cases (25%). 15 were full blown or mosaic numerical X chromosome abnormalities (8.5%), 10 were full blown or mosaic X-chromosome structural anomalies (5.7%), one was X-autosome translocation (0.5%), 3 were autosomal anomalies (1.7%), 12 were XY karyotype (6.8%), one was 45,X/46,XY mosaic and 2 were full blown or mosaic structural anomalies of Y chromosome (1.7%). The prevalence of chromosomal abnormalities was 25% in this large series of Turkish women with primary amenorrhea or premature ovarian insufficiency, most cases involving X-aneuploidy or X-structural abnormalities or 46,XY karyotype. High prevalence of chromosomal abnormalities is associated with POI starting at an early age (average age: 26 years).