ABSTRACT
Objective:To evaluate the activity of iduronate-2-sulfatase (IDS) in fetal villi and peripheral blood plasma of pregnant women at high risk of mucopolysaccharidosis type Ⅱ (MPS Ⅱ), and to discuss the application of gene analysis in prenatal diagnosis of MPS Ⅱ.Methods:The enzymatic testing and gene analysis results of 23 pregnant women at high risk of MPS Ⅱ, who underwent prenatal diagnosis in Guangzhou Women and Children′s Medical Center from February 2013 to December 2020, were analyzed retrospectively.The IDS activity in fetal villi (30 cases) and plasma (28 cases) was detected by artificial substrate fluorescence.The IDS activity in fetal villi (28 cases) and plasma (34 cases) of normal pregnant women was taken as control.Meanwhile, the fetal villi of both pregnant women at high risk of MPS Ⅱ and normal pregnant women were also analyzed by gene testing and for fetal sex identification.Data were compared between groups by the independent samples t test. Results:The normal reference values of the IDS activity in fetal villi and plasma of normal pregnant women were(71.2±23.4) nmol/(mg·4 h) and (611.1±114.5) nmol/(mL·4 h), respectively.Among the 30 cases of high-risk fetal villi, the IDS activity in fetal villi of 8 affected male fetuses was (1.7±0.3) nmol/(mg·4 h), which was significantly lower than that of 11 unaffected male fetuses (83.2±6.3) nmol/(mg·4 h) and that of 9 non-carrier female fetuses (80.0±7.5) nmol/(mg·4 h) ( t=10.8, 8.8; all P<0.01). Meanwhile, the IDS activity was measured in the maternal peripheral plasma of 28 pregnant women at high risk of MPS Ⅱ.Among them, the IDS activity in 8 affected male fetuses was(225.4±20.5) nmol/(mL·4 h), which was significantly lower than that in non-affected male fetuses[(451.0±15.1) nmol/(mL·4 h)] and that in non-carrier female fetuses[(467.7±45.3)nmol/(mL·4 h)]. Eight known pathogenic mutations were found in 30 cases at high risk of MPS Ⅱ of fetal villi, and the mutation types were c. 1048A>C, c.212G>A, c.514C>T, c.257C>T, c.425C>T, and c. 998C>T.Of the 8 cases, 6 affected male fetuses had significantly reduced IDS activities, and the other 2 female carriers had normal IDS enzyme activities. Conclusions:The IDS activity in fetal villi and peripheral plasma of pregnant woman is consistent with the gene analysis results.The IDS activity has an important reference value for the prenatal diagnosis of MPS Ⅱ in the first trimester.When no genetic mutations are found in the probands or the pathogenicity of the new mutation remains unclear, the IDS activity in fetal villi can be detected separately for the prenatal diagnosis of MPS Ⅱ.
ABSTRACT
Objective@#To report clinical feature and results of genetic analysis of 3 patients from 2 families with Finnish variant late infantile neuronal ceroid lipofuscinosis.@*Methods@#The clinical and ultrastructural features of 3 patients with progressive neurodegenerative diseases were retrospectively analyzed from October 2014 to December 2016 in Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center. The whole exon sequencing and Sanger sequencing were used to analyze the molecular genetics of the patients and their parents.@*Results@#The probands were 11 years and 3 moths, 9 years and 1 month,10 years and 1 month old. All were normal at birth, and from 5-6 years old they began to develop "regression of cognition and motion, impaired vision". Physical examination at the first consultation: clear minded butignorant, unable to speak and understand instructions, unable to stand up and sit alone, unable to maintain postureupright. The brain magnetic resonance imaging(MRI) indicated diffuse cerebral and cerebellar atrophy, white matter damage. Blood biochemistry, lactic acid, acid-base balancewere normal. Electron microscopic examination of peripheral blood lymphocytes showed swelling of the nucleus, autophagy, intracellular massive deposits and abnormal vacuoles. Two compound heterozygous c.334C> T (p.Arg112Cys) and c.595C> T (p.Arg199Ter) mutations of CLN5 gene were identified in the two siblings, and the proband 3 was c.335G> A (p.Arg199His) homozyousmutation, which were inherited from their unaffected parents.@*Conclusions@#The 3 cases with Finnish variant late infantileneuronal ceroid lipofuscinosises were normal at birth, cognitive and motor function was regressed at preschool age.Brain MRI showed whole brain atrophy, white matter lesions, there were no bovious difference from other neurodegenerative diseases. Blood biochemistry and pathological examination of lymphocytes had no specific changes. The pathogenic genes were CLN5,most are inherited in autosomal recessive way.