Clinical and genetic analysis of a patient with autosomal recessive congenital ichthyosis due to compound heterozygous variants of ALOX12B gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a pediatric patient suspected for Autosomal Recessive Congenital Ichthyosis (ARCI).@*METHODS@#Clinical data of the patient was analyzed. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Next-generation sequencing (NGS) was then carried out. Candidate variants were confirmed by Sanger sequencing. A variety of bioinformatic tools including Mutation Taster, PROVEAN, and PolyPhen2 were used to predict the pathogenicity of the variants based on guidelines from the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#The patient, a 1-month-and-7-day-old male, had presented with cutaneous erythema and fine scaling of the whole body. NGS revealed that he has harbored compound heterozygous variants c.1579G>A (p.Val527Met) (paternal) and c.923T>C (p.Leu308Pro) (maternal) of the ALOX12B gene. The former was known to be likely pathogenic, while the latter was unreported previously and categorized as "likely pathogenic" based on the ACMG guidelines. Based on the clinical and genetic findings, the patient was diagnosed with ARCI.@*CONCLUSION@#The c.1579G>A and c.923T>C variants of the ALOX12B genes probably underlay the ARCI in this patient. Above finding has enriched the spectrum of ALOX12B mutations and enabled molecular diagnosis of the patient, based on which genetic counseling and prenatal diagnosis may be provided.

Expression of cyclooxygenase-2 and 12-lipoxygenase in human breast cancer and their relationship with HER-2/neu and hormonal receptors: impact on prognosis and therapy.

BACKGROUND: A number of studies have shown over-expression of cox-2 in breast cancer. Also it has been recorded that human breast cancer expresses high level of cox-2 and 12-lipoxygenase which may be beneficial in future therapy plan for those patients. AIMS: The present study aims to examine the level of transcripts of cox-2 and 12-lipoxygenase in Egyptian breast cancer patients and to compare between the expressions of both enzymes and TNM staging, hormone receptors status (including estrogen and progesterone) and HER2/neu expression. MATERIALS AND METHODS: Total cellular RNA was extracted from 64 frozen tissue samples of breast carcinoma and their corresponding normal adjacent tissues. Cox-2 and 12-lipooxygenase expressions were detected using RT-PCR. Hormonal receptors as well as HER2/neu were detected immuno-histochemically for each patient. RESULTS: About 47 and 62.5% of carcinoma samples showed over-expression of cox-2 and 12-lipooxygenase respectively as compared to their corresponding normal tissues. The results revealed that cox-2 significantly associated with TNM staging (P = 0.0047) and hormonal receptors status (P = 0.0201). The relationship between cox-2 and HER2/neu expression was close to a significant value (P = 0.0747). 12-lipooxygenase showed only significant association with TNM staging (P = 0.0076). Neither hormonal receptors nor HER2/neu showed significant association with this enzyme. CONCLUSION: Elevated levels of cox-2 and 12-lipoxygenase expression were detected in human breast cancer. Also, the results revealed that cox-2 and 12-lipooxygenase mRNA expressions are associated with TNM staging in human breast cancer. Furthermore, there is an inverse association between cox-2 expression and hormonal receptor status. This observation may drive us to the possible role of those two enzymes in determining the plan of therapy of breast cancer patients.