1.Gene Analysis Of Pituitary Stalk Interruption Syndrome In A Pedigree And Literature Review 2.Gene Analysis Of Osteogenesis Imperfecta Classification In APedigree And Literature Review

BackgroundPituitary stalk interruption syndrome (PSIS) was reported by Fujisawa described as transection of pituitary stalk for the first time in 1987. PSIS is caused by the deficiency of hypophyseal hormone(s) like growth hormone (GH) resulting from the transection or thinness of the pituitary stalk, and the lack of stimulation from the hypothalamus to the pituitary via circulation. Patients with PSIS often show symptoms as short stature, developmental retardation and so on.There are two main opinions about the pathogenesis of PSIS. One opinion is that the perinatal injuries can give rise to the syndrome due to the high percentage of perinatal events, such as breech delivery, cesarean delivery and neonatal asphyxia, in PSIS patients. The other hypothesis is that PSIS can be the result of variation of genes. A few experiments have been carried out to prove it and several relative genes have been found. But the mode of inheritance about this disease is uncertain.Nowadays, magnetic resonance imaging (MRI) and the tests about hormones are the main basis of diagnosis. The MRI of PSIS patients shows a classic triad which consists of:(1) an interrupted or thin pituitary stalk, (2) an absent or ectopic posterior pituitary (EPP), and (3) anterior pituitary hypoplasia or aplasia.Generally, the treatment method of the disease is hormone replacement therapy (HRT), including the replacement of growth hormone (GH), sex hormone and so on depending on personal conditions.ObjectiveHere, we planned to investigate the clinical and genetic characteristics of one Chinese pedigree and summarize the advance in pathogenesis, diagnosis, and managements.Subjects and MethodsWe collected the blood of the PSIS proband and her family members, and extracted DNA from the blood. The DNA was identified and screened for mutations in OTX2 gene, LHX4 gene, HESX1 gene and SOX3 gene. The manifestations, test results and other relating data were analyzed based on the review of past articles.ResultsThe proband was characterized by 1st generation, full-term normal delivery, no birth asphyxia, below the average school record, growth retardation. X-ray showed that the bone age was younger than real age. MRI showed small pituitary body, ectopic posterior pituitary, and thin pituitary stalk. A heterozygote was found in 0TX2 gene. A homozygote (c.983A>G, p.N328S) was found in LHX4 gene, which was proved to be meaningless. And no variation was found in LHX4 gene, HESX1 gene and SOX3 gene. During the half year following the use of hormone replacement therapy (HRT) showed obvious curative effect.ConclusionNo significant gene mutation suggested to be the causative agents of PSIS was found. Considering there was no particular influence during pregnant and perinatal period of the patient’s mother, we can infer that other factors exist except above causes of PSIS, which providing a reference to the research of this disease. The pathogenesis, diagnosis, managements and other facts of PSIS need deeper research to know it.BackgroundOsteogenesis imperfecta (01), also named as brittle bone disease, is an uncommon genetic disease which occurs in about 1 in 10,000 to 20,000 live births. The specific clinical manifestation is fracture due to the increased skeletal fragility. And skeletal deformity, joint laxity, and scoliosis can show in OI patients, too. What’s more, symptoms in other tissues and organs like hearing loss, dentinogenesis imperfecta, blue/gray sclerae, and hypercalciuria can also be observed frequently.The major pathogenic genes are type I collagen synthesis genes (COL1A1 and COL1A2), covering more than 90% in OI patients. Besides, there are many more genes are concerned about this disease. They can affect the synthesis, folding, modification and other procedures during the type I collagen produce and function process.Nowadays, no effective treatment has been found. Medicine and surgery can be chosen to deal with the disease base on the prevention of fracture. However satisfied therapeutic benefits can not be predicted to both of them. Available medicines include bisphosphonates, growth hormone and so on. Those medicines can not improve the situation obviously. Even they may increase the risk of fracture. While the function of surgery is poor, either. The patient will take the risk of the dislocation of the implants and the impairment on bones.The severity depends on the type of OI which decides the prognosis of the patient. Patients with mild manifestations can take care of themselves very well. While there are also some types of OI lethal with undesirable endings. So effective measurements should be discovered as soon as possible to improve the quality of life of the OI patients.ObjectiveThe aim was to investigate the clinical and genetic characteristics of the Chinese OI pedigree and summarize the advance in pathogenesis, diagnosis, and managements.Subjects and MethodsThe blood of the OI proband and her family members was collected, and DNA was extracted from the blood. The DNA was identified and screened for mutations in 6 candidate genes—COL1A1, COL1A2, CRTAP, PPIB, IFITM5, and SERPINH. The manifestations, test results and other relating data were analyzed based on the review of past articles.ResultsTwo patients were diagnosed in this OI family—the proband and her daughter. The proband was full-term breech delivery, with birth asphyxia. Since 5 months old, the proband began to fracture frequently. She was 130cm in height and 52kg in weight with 36+5 week pregnancy at diagnosis. The stature was short, and the left leg was shorter than the right one. The face was in inverted triangle shape. And the sclera of both eyes were blue. Her daughter was full-term cesarean delivery without asphyxia. The body length was 42cm and weight was 2330g at birth. The daughter also shows an inverted triangle-shape facial, and binocular blue sclera. A heterozygote mutation was found in COL1A2 gene c.1009G>T, p.Gly337Cys in both the proband and her daughter. The replacement of Gly by Cys caused the instability of type I collagen structure resulting in a series of abnormal conditions.ConclusionIn this pedigree,OI is dominant inherited. The heterozygote mutation is predicted to be the main reason for the incidence of OI in the two patients. The proband got the replacement through the mutation of the gene. And the daughter inherited this mutation from her mother and showed similar symptoms.