Genetic Implications in High-Risk Pregnancy and Its Outcome: A 2-year Study. The authors evaluated high-risk pregnancies (n=460) for medical conditions, hereditary disorders, or major anomalies. Parental consanguinity and endogamy were noted in 67 and 71.3%, respectively. All pregnant mothers underwent 1st-trimester biochemical testing (plasma protein-A, α-fetoprotein (AFP), human chorionic gonadotropin (hCG) and serial ultrasound examinations. Seventy mothers needed 2nd-trimester biochemical testing (AFP, hCG, and estriol), and 62 underwent amniocentesis where G-banding karyotype, fluorescence in situ hybridization and targeted molecular testing for specific gene disorders were conducted . High quality fetal ultrasound was performed when brain malformations were suspected, while 16 fetuses required brain MRI examination. Eighteen infants were confirmed to have a congenital malformation/genetic disorders. Five were diagnosed prior to birth, but 13 were diagnosed after birth. Parental consanguinity and endogamy were more frequent among these high-risk pregnancies, but despite strong vigilance, many cases can be diagnosed only after birth. A structured multidisciplinary team of specialists in fetal medicine, clinical genetics, and neonatology is needed to provide good genetic services.
Genotype-Phenotype Correlation of G6PD Mutations among Central Thai Children with G6PD Deficiency. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked inherited erythroenzymopathy in Thailand. The authors studied 102 children including 73 males (71.6%) and 29 females (28.4%) and identified 12 different mutations. G6PD Viangchan (871G > A) and G6PD Canton (1376G > T) were the first (46.2%) and the second (15.4%) most common identified mutations among both male and female G6PD-deficient individuals, respectively. All affected males were hemizygous for G6PD mutations and had an average G6PD level of 16.7 ± 11.5 (3-76) IU/ml.RBC. Majority of female patients (27 in 29, 93.1%) were heterozygous for G6PD mutations and had an average G6PD level of 133.6 ± 43.4 (9-195) IU/ml.RBC. Two female patients (6.9%) were either homozygous or compound heterozygous for the mutations and had G6PD level in the affected male range (35 and 10 IU/ml.RBC). Only 1 in 27 heterozygous females (3.7%) had G6PD level in the affected male range (9 IU/ml.RBC) which is possibly explained by nonrandom X-chromosome inactivation. This study characterizes the molecular heterogeneity of G6PD variants causing G6PD deficiency in Thai children.
Genetic testing for unexplained perinatal disorders. Genetic diseases may account for a considerable proportion of unexplained perinatal disorders such as stillbirth, congenital structural anomalies, and critical illnesses. Exome and genome sequencing (ES and GS) can be useful in these infants. Despite the cost implications, having a specific genetic diagnosis provides significant clinical utility, including improved prognostication of the outcome, tailored therapy, directed testing for associated syndromic manifestations, referral to appropriate subspecialists, family planning, and redirection of care.
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