Phenotypic spectrum of BLM- and RMI1-related Bloom syndrome.

Bloom syndrome (BS) is an autosomal recessive disorder with characteristic clinical features of primary microcephaly, growth deficiency, cancer predisposition, and immunodeficiency. Here, we report the clinical and molecular findings of eight patients from six families diagnosed with BS. We identified causative pathogenic variants in all families including three different variants in BLM and one variant in RMI1. The homozygous c.581_582delTT;p.Phe194* and c.3164G>C;p.Cys1055Ser variants in BLM have already been reported in BS patients, while the c.572_573delGA;p.Arg191Lysfs*4 variant is novel. Additionally, we present the detailed clinical characteristics of two cases with BS in which we previously identified the biallelic loss-of-function variant c.1255_1259delAAGAA;p.Lys419Leufs*5 in RMI1. All BS patients had primary microcephaly, intrauterine growth delay, and short stature, presenting the phenotypic hallmarks of BS. However, skin lesions and upper airway infections were observed only in some of the patients. Overall, patients with pathogenic BLM variants had a more severe BS phenotype compared to patients carrying the pathogenic variants in RMI1, especially in terms of immunodeficiency, which should be considered as one of the most important phenotypic characteristics of BS.

Novel and recurrent XYLT1 mutations in two Turkish families with Desbuquois dysplasia, type 2.

Desbuquois dysplasia (DBQD) is an autosomal recessive skeletal disorder characterized by growth retardation, joint laxity, short extremities, and progressive scoliosis. DBQD is classified into two types based on the presence (DBQD1) or absence (DBQD2) of characteristic hand abnormalities. CANT1 mutations have been reported in both DBQD1 and DBQD2. Recently, mutations in the gene encoding xylosyltransferase 1 (XYLT1) were identified in several families with DBQD2. In this study, we performed whole-exome sequencing in two Turkish families with DBQD2. We found a novel and a recurrent XYLT1 mutation in each family. The patients were homozygous for the mutations. Our results further support that XYLT1 is responsible for a major subset of DBQD2.

Outcomes of Osteosarcoma in Children Without High-Dose Methotrexate: Could It Be Less Toxic Without Effecting Survival Rates?

Background: Osteosarcoma (OS) is the most common primary bone sarcoma in childhood. High-dose methotrexate, doxorubicine, cisplatin, and/or ifosfamide combinations are used as standard treatment in chemotherapy and could cause serious toxicity. Another alternative chemotherapy protocol is consisting of epirubicin, ifosfamide, and cisplatin (ECI), which we use in our center. The aim of this study was to evaluate the patients with OS who were treated with ECI protocol, retrospectively. Methods: Forty-three patients with OS diagnosed at our center between December 1995 and September 2017 were evaluated retrospectively. Results: The mean follow-up period was 31 months (5-145 months). Recurrence was detected in 15 of 43 patients. When the factors affecting relapse are examined, recurrence was higher in patients who were older than 10 years at the time of diagnosis, upper extremity involvement, osteoblastic, and chondroblastic subgroups, but there was no statistically significant difference. Five-year and 10-year overall survival rates were 67.4% and 58.9%, and event-free survival rates were 54% and 47.3%, respectively. While 5-year overall survival rate was 86.7% in nonrecurrent cases, this rate was 40.9% in recurrent cases and this difference was statistically significant (p = 0.023). Just two patients died because of the toxicity. Conclusion: The prognosis of OS is still poor in relapse cases, so the choice of chemotherapy for neoadjuvant and adjuvant therapy is vital. When the risk of toxicity is also considered, the first step of ECI protocol is seen as a preferable treatment option because the survival rates are similar to the literature.