Case Report: A Homozygous Mutation (p.Y62X) of Phospholipase D3 May Lead to a New Leukoencephalopathy Syndrome.

Leukodystrophies are a heterogeneous group of inherited disorders with highly variable clinical manifestations and pathogenetic backgrounds. At present, variants in more than 20 genes have been described and may be responsible for different types of leukodystrophies. Members of the phospholipase D family of enzymes catalyze the hydrolysis of membrane phospholipids. Meanwhile, phospholipase D3 (PLD3) has also been found to exhibit single stranded DNA (ssDNA) acid 5' exonuclease activity. Variants in phospholipase D3 (PLD3) may increase the risk of Alzheimer's disease and spinocerebellar ataxia, but this hypothesis has not been fully confirmed. In this study, we identified a novel homozygous mutation (NM_012268.3: c.186C>G/ p.Y62X) of PLD3 in a consanguineous family with white matter lesions, hearing and vision loss, and kidney disease by whole exome sequencing. Real-time PCR revealed that the novel mutation may lead to non-sense-mediated messenger RNA (mRNA) decay. This may be the first case report on the homozygous mutation of PLD3 in patients worldwide. Our studies indicated that homozygous mutation of PLD3 may result in a novel leukoencephalopathy syndrome with white matter lesions, hearing and vision loss, and kidney disease.

[Prenatal diagnosis and treatment of fetal choroid plexus cysts].

OBJECTIVE: To discuss the clinical management and significance of the prenatal diagnosis of Fetal Choroid Plexus Cysts (CPC). METHODS: From May 2004 to March 2007, 55 cases of fetal CPC diagnosed by B-ultrasound during second trimester were prospectively studied. Each case was studied regarding fetal chromosome karyotype, disappearance weeks of the cyst, the clinical outcome and follow-up results respectively. RESULT: The cases were diagnosed during 16 - 25 gestational weeks. The diameters of the cysts varied from 0.2 cm to 2.4 cm. There were 25 cases of bilateral cysts and 30 cases of unilateral or 50 cases of isolated CPC and 5 cases of complicated CPC. The cysts of all cases who continued pregnancy disappeared before 28 weeks. Fetal chromosome karyotypes were obtained in 50 cases. Among them, two cases were 18-trisomy, and one case was 21-trisomy. Five cases were terminated pregnancy because of abnormal chromosome karyotype or malformation during second trimester. One neonate was diagnosed as ventricular septal defect among 50 cases of follow up. Among these six cases, three were from advanced-age pregnant women, five cases were with abnormal fetal structure and five cases were with the diameter of bilateral or unilateral cysts more than 1.0 cm. CONCLUSION: (1) Fetal CPC can be diagnosed during second trimester, and the majority disappear before 28 gestational weeks. (2) High risk factors for fetal abnormal chromosome karyotype may be: advanced-age pregnant women, abnormal structure of fetus, and the diameter of bilateral or unilateral cyst more than 1.0 cm. It is suggested that fetal CPC with the high risks should receive fetal chromosome karyotype test during pregnancy.

[Thyroid functional changes of normal human fetus and newborns].

OBJECTIVE: To study the changes of the thyroid hormones level of human fetus and newborns. METHODS: More than 71 cases of medically indicated cordocentesis have been done in 16 -36 gestational weeks in our hospital during last three years. Among them, 71 fetus who were free of diseases and their maternal thyroid function were normal were included into the study group. The blood samples were sent to analysis of thyroxine (T(4)), triiodothyroxine (T(3)), free thyroxine (FT(4)), free triiodothyroxine (FT(3)) and thyrotropin (TSH). 140 umbilical cord blood samples taken at the time of term delivery were sent to analysis of FT(4), FT(3) and TSH as a control. Normal range of different gestational weeks was calculated. Statistical analysis was done for the changes of all these thyroid hormones before 28 weeks and after. RESULTS: All the thyroid hormones can be detected in 16 weeks of pregnancy, FT(4) already reaches the top level of adults (5.8 +/- 2.6) pmol/L and will continually increase with the increase of gestational age. There was a parallel increment of all the fetal thyroid hormone concentrations with the gestational age. The concentrations of T(4), T(3) and FT(4) have a rapidly increase after 28 weeks and have a statistically significant difference from (2.8 +/- 1.8) nmol/L, (37.2 +/- 27.2) nmol/L and (10.6 +/- 3.1) pmol/L, respectively to (5.8 +/- 2.6) nmol/L, (55.9 +/- 33.3) nmol/L, (13.0 +/- 4.5) pmol/L, respectively. TSH level of fetus was increased gradually along the gestation, reaching the up level of the adults at the 20 weeks and peaking at the birth time. While the T(3) and FT(3) keep in a lower level in gestation. CONCLUSIONS: Fetal thyroid hormones increase with the gestational age. The diagnosis of congenital fetal thyroid hormone malfunction in the second half of the pregnancy should be monitored mainly by the T(4), FT(4) and TSH levels in different gestational age. For this consideration, to set up a reliable data for normal human fetus thyroid hormone concentrations is a very important and essential step to provide a practical guide for doctors to do intra-uterine diagnosis and treatment of associated high-risk groups. The peaking level of TSH at the birth time will surely company the changing of other thyroid hormones, so it might not be the best time to screening the congenital thyroid malfunction at the 72 hours after birth.