• Childhood Kidney Diseases
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• v.8 no.1
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• pp.18-25
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• 2004

Purpose : Alport syndrome is clinically characterized by hereditary progressive nephritis causing ESRD with irregular thickening of the GBM and sensory neural hearing loss. The mutations of type IV collagen gene(COL4A5) located on the long arm of X chromosome is considered responsible for most of the structural abnormalities in the GBM of Alport patients. Since no definite clinical prognostic predictor has been reported in the disease yet, we designed this study to evaluate the significance of genetic polymorphism of the angiotensin converting enzyme in children with Alport syndrome as a prognostic factor for disease progression. Methods : ACE I/D genotype were examined by PCR amplification of the genomic DNA in 12 patients with Alport syndrome and 12 of their family members. Alport patients were divided into two groups; the conservative group, those who had preserved renal function for more than 10 years of age, the early CRF group, those who had progressed to CRF within 10 years of age. Results : The mean age of onset was $3.45{\pm}2.4$ years in the conservative group, $4.4{\pm}1.2$ years in the early CRF group. Sex ratios were 5:3 and 2:1 in each group. Among 12 cases of patients, 4 cases were in early CRF group and their mean duration of onset to CRF was 4.5 yews(8.9 years of age). Eight patients(67%) were in the conservative group and they had normal renal function for more than 10 years of age(mean duration of renal preservation was 10.6 years). The incidence of II type ACE gene were in 25.0%(3 cases), ID type in 41.7%(5 cases), DD type in 33.3%(4 cases). There was no significant difference between Alport patient and normal control(II type 44.3%, ID type 40.9%, DD type 14.8%). The incidence of DD type of early CRF group were higher than that of the conservative group(75% vs 12.5%)(p<0.05). There was no difference in ACE gene polymorphism between normal Alport family members and control group. Conclusion : Even though there was no significant difference of ACE polymorphism between Alport patients and the normal control group, the incidence of DD type is significantly increased in early CRF group which means DD type of ACE polymorphism has a possibility of being a predictor for early progression to CRF in Alport patients.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.2
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• pp.99-110
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• 2008

Objectives: Preimplantation genetic diagnosis (PGD) has become an assisted reproductive technique for couples carrying genetic conditions that may affect their offspring. Osteogenesis imperfecta (OI) is an autosomal dominant disorder of connective tissue characterized by bone fragility and low bone mass. At least 95% of cases are caused by dominant mutations in the COL1A1 or COL1A2. In this study, we report on our experience clinical outcomes with 5 PGD cycles for OI in two couples. Methods: Before clinical PGD, we assessed the amplification rate and allele drop-out (ADO) rate of alkaline lysis and nested PCR protocol using heterozygous patient's single lymphocytes in the pre-clinical diagnostic tests for OI. We performed 5 cycles of PGD for OI by nested PCR for the causative mutation loci, COL1A1 c.2452G>A and c.3226G>A, in case 1 and case 2, respectively. The PCR products were analyzed by agarose gel electrophoresis, restriction fragment length polymorphism (RFLP) analysis with HaeIII restriction enzyme in the case 1 and direct DNA sequencing. Results: We confirmed the causative mutation loci, COL1A1 c.2452G>A in case 1 and c.3226G>A in case 2. In the pre-clinical tests, the amplification rate was 94.2% and ADO rate was 22.5% in case 1, while 98.1% and 1.9% in case 2, respectively. In case 1, a total of 34 embryos were analyzed and 31 embryos (91.2%) were successfully diagnosed in 3 PGD cycles. Eight out of 19 embryos diagnosed as unaffected embryos were transferred in all 3 cycles, and in the third cycle, pregnancy was achieved and a healthy baby was delivered without any complications in July, 2005. In case 2, all 19 embryos (100.0%) were successfully diagnosed and 4 out of 11 unaffected embryos were transferred in 2 cycles. Pregnancy was achieved in the second cycle and the healthy baby was delivered in March, 2008. The causative locus was confirmed as a normal by amniocentesis and postnatal diagnosis. Conclusions: To our knowledge, these two cases are the first successful PGD for OI in Korea. Our experience provides a further demonstration that PGD is a reliable and effective clinical techniques and a useful option for many couples with a high risk of transmitting a genetic disease.

• Journal of Genetic Medicine
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• v.8 no.2
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• pp.89-99
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• 2011

Over the years Korean health care system has improved in delivery of quality care to the general population for many areas of the health problems. The system is now being recognized in the world as the most cost effective one. It is covered by the uniform national health insurance policy for which most people in Korea are mandatory policy holders. Genetic counseling service, however, which is well recognized as an integral part of clinical genetics service deals with diagnosis and management of genetic condition as well as genetic information presentation and family support, is yet to be delivered in comprehensive way for the patients and families in need. Two major obstacles in providing genetic counseling service in korean health care system are identified; One is the lack of recognition for the need for genetic counseling service as necessary service by the national health insurance. Genetic counseling consumes a significant time in delivery and the current very low-fee schedule for physician service makes it very difficult to provide meaningful service. Second is the critical shortage of qualified professionals in the field of medical genetics and genetic counseling who can provide the service of genetic counseling in clinical setting. However, recognition and understanding of the fact that the scope and role of genetic counseling is expanding in post genomic era of personalized medicine for delivery of quality health care, will lead to the efforts to overcome obstacles in providing genetic counseling service in korean health care system. Only concerted efforts from health care policy makers of government on clinical genetics service and genetic counseling for establishing adequate reimbursement coverage and professional communities for developing educational program and certification process for professional genetic counselors, are necessary for the delivery of much needed clinical genetic counseling service in Korea.