Prenatal diagnosis of Wolf-Hirschhorn syndrome characterized by severe fetal growth restriction in three fetuses / 中华围产医学杂志

Objective:To analyze the prenatal clinical characteristics and genetic etiology of Wolf-Hirschhorn syndrome manifested by severe fetal growth restriction (FGR).Methods:Clinical data of three pregnant women admitted to Changsha Hospital for Maternal and Child Health Care from 2018 to 2020 due to severe FGR with or without other malformations diagnosed by prenatal ultrasound were collected. Amniotic fluid samples obtained by ultrasound-guided amniocentesis were analyzed by conventional G-banding staining technique and single nucleotide polymorphism array (SNP array). Parental peripheral blood cells were collected for SNP array to verify the source of variation.Results:(1) The karyotypes of both case 1 and 2 were normal, while case 3 had an abnormal karyotype of 46,XN,der(4)(9pter→9p23::4p15.31→4qter). (2) SNP array indicated a 7.8 Mb microdeletion in 4p16.3p16.1 cytoband in case 1 and a 5.5 Mb microdeletion in 4p16.3p16.2 cytoband in case 2, which were both de novo copy number variations. Case 3 harbored a 19.88 Mb deletion in 4p16.3p15.31 and a 10.89 Mb duplication in 9p24.3p23. (3) All three fetuses were diagnosed as Wolf-Hirschhorn syndrome, and their parents chose to terminate the pregnancies after genetic counseling. Conclusions:Considering the possibility of genetic disease, invasive prenatal diagnosis is suggested when prenatal ultrasonography showed severe FGR, regardless of other malformations, to clarify the cause and guide genetic counseling.

Biochemical and genetic characteristics of 40 neonates with carnitine deficiency / 中南大学学报(医学版)

OBJECTIVES@#Primary carnitine deficiency (PCD) is a rare fatty acid metabolism disorder that can cause neonatal death. This study aims to analyze carnitine levels and detect SLC22A5 gene in newborns with carnitine deficiency, to provide a basis for early diagnosis of PCD, and to explore the relationship between carnitine in blood and SLC22A5 genotype.@*METHODS@#A total of 40 neonates with low free carnitine (C0G (p.Y251C), c.495 C>A (p.R165E), and c.1298T>C (p.M433T). We found 14 PCD patients including 2 homozygous mutations and 12 heterozygous mutations, 14 with 1 mutation, and 12 with no mutation among 40 children. The C0 concentration of children with SLC22A5 gene homozygous or complex heterozygous mutations was (4.95±1.62) μmol/L in the initial screening, and (3.90±1.33) μmol/L in the second screening. The C0 concentration of children with no mutation was (7.04±2.05) μmol/L in the initial screening, and (8.02±2.87) μmol/L in the second screening. There were significant differences between children with homozygous or compound heterozygous mutations and with no mutation in C0 concentration of the initial and the second screening (both @*CONCLUSIONS@#There are 5 new mutations which enriched the mutation spectrum of SLC22A5 gene. C0<5 μmol/L is highly correlated with SLC22A5 gene homozygous or compound heterozygous mutations. Children with truncated mutation may have lower C0 concentration than that with untruncated mutation in the initial screening.

Establishment of hemophilia A patient-specific inducible pluripotent stem cells with urine cells / 中华医学遗传学杂志

OBJECTIVE To generate hemophilia A (HA) patient-specific inducible pluripotent stem cells (iPSCs) and induce endothelial differentiation. METHODS Tubular epithelial cells were isolated and cultured from the urine of HA patients. The iPSCs were generated by forced expression of Yamanaka factors (Oct4, Sox2, c-Myc and Klf4) using retroviruses and characterized by cell morphology, pluripotent marker staining and in vivo differentiation through teratoma formation. Induced endothelial differentiation of the iPSCs was achieved with the OP9 cell co-culture method. RESULTS Patient-specific iPSCs were generated from urine cells of the HA patients, which could be identified by cell morphology, pluripotent stem cell surface marker staining and in vivo differentiation of three germ layers. The teratoma experiment has confirmed that such cells could differentiate into endothelial cells expressing the endothelial-specific markers CD144, CD31 and vWF. CONCLUSION HA patient-specific iPSCs could be generated from urine cells and can differentiate into endothelial cells. This has provided a new HA disease modeling approach and may serve as an applicable autologous cell source for gene correction and cell therapy studies for HA.