Preimplantation genetic testing for monogenic/single gene disorders in a family with Molybdenum co-factor deficiency / 中华医学遗传学杂志

OBJECTIVE@#To carry out preimplantation genetic testing for monogenic/single gene disorders (PGT-M) for a Chinese family affected with Molybdenum co-factor deficiency due to pathogenic variant of MOCS2 gene.@*METHODS@#A family with molybdenum co-factor deficiency who attended to the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region in April 2020 was selected as the research subject. Trophoblast cells were biopsied from blastocysts fertilized by intracytoplasmic sperm injection. Embryos carrying the MOCS2 gene variant and chromosome copy number variation (CNV) of more than 4 Mb were detected by single-cell whole genome amplification, high-throughput sequencing and single nucleotide polymorphism typing. Embryos without or carrying the heterozygous variant and without abnormal chromosome CNV were transplanted. During mid-pregnancy, amniotic fluid sample was collected for prenatal diagnosis to verify the results of PGT-M.@*RESULTS@#Eleven oocytes were obtained, among which three blastocysts were formed through culturing. Results of genetic testing suggested that one embryo was heterozygous for the maternally derived MOCS2 gene variant and without chromosomal CNV. Following embryo transfer, intrauterine singleton pregnancy was attained. Prenatal diagnosis by amniocentesis at 18 weeks of gestation revealed that the MOCS2 gene variant and chromosomal analysis results were both consistent with that of PGT-M, and a healthy male infant was born at 37+5 weeks of gestation.@*CONCLUSION@#PGT-M has helped the couple carrying the MOCS2 gene variant to have a healthy offspring, and may become an important method for couples carrying other pathogenic genetic variants.

Inherited canine copper toxicosis in Australian Bedlington Terriers

Inherited copper toxicosis in Bedlington Terriers (CTBT) is a copper associated hepatopathy caused by an autosomal recessive genetic defect of gene involving copper metabolism. To compare clinical and histopathological findings with previous reports and to expand our knowledge for future genetic studies, 18 terriers were clinically and histopathologically examined in this study. Pedigree information and dietary history were obtained from the owners before a thorough clinical examination was undertaken. Following the examination, a blood sample was collected for haematology, biochemistry and genetic analysis and a urine sample for urinalysis. Seven dogs were also liver biopsied for histopathology, histochemistry and electron microscopy. In this study, plasma alanine transaminase (ALT) activity was highly concordant with DNA marker test results and was the most reliable and sensitive biochemical test measured. Also clinical and biochemical copper toxicosisaffected states were noticed in a genotyped carrier dog. Histopathological and electron microscopy findings showed that the severity of the lesion was more closely correlated to the presence of clinical signs than to hepatic copper concentration. In addition, the involvement of apoptosis and p53 gene was observed in electron microscopy. The general findings related to CT-BT in this study was similar to those previously reported except few differences in histopathology and electron microscopy.