The Molecular Basis Of Oculocutaneous Albinism Type 1 And Prader-Willi Syndrome

In this study, we will analyze the molecular basis on oculocutaneous albinism type 1 and Prader-Willi syndrome.Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders characterized by reduced or absent biosynthesis of melanin in melanocytes of the skin, hair follicle and eyes. It is the most common form of albinism and can be separated into four types: OCA1, OCA2, OCA3 and OCA4. OCA1, which results from mutations of the tyrosinase, is one of the most serious and common types of OCA.In order to explore the mutation spectrum of TYR gene in China, we analyzed the TYR gene of 60CA1 patients by use of direct sequencing, heteroduplex analysis (HA) and denaturing high performance liquid chromatography (DHPLC). We had detected 9 kinds of mutations, including 4 missense mutations (R77Q, K142M, E294K and W400L), 3 nonsense mutations (R116X, R278X and E281X), 1 insertion mutation (232insGGG) and 1 splice site mutation (IVS1-3C＞G). E281X is a novel mutation which hasn't reported yet before. It seems that W400L is one of the most common mutations, which accounts for about 33.3% (4/12) in Chinese OCA1 alleles. The results show that the Chinese population TYR gene mutation spectrum is different from other countries'.In addition, we analyzed on the fetal TYR gene mutation with a pregnant woman who had a baby with OCA1 before. The gene diagnosis has revealed that the fetus didn't carry either the father's TYR mutational gene (232insGGG) or the mother's TYR mutational gene (E281X). That is to say the fetal genotype is normal. The child presented with a normal appearance at birth.Our research provides data for gene diagnosis and prenatal gene diagnosis which is aim directly at OCA1, having profound practice meaning in the aspect of albinism genetic counseling, prevention and aristogenesis in our country.Prader-Willi syndrome (PWS) is an example genetic disorder due to a loss of paternal imprinted gene expression in the 15q11-q13. It's characterized by neonatal hypotonia resulting in poor sucking, hyperphagia in childhood leading to serve obesity, short stature, hypogonadism, mental retardation.Aiming directly at STR polymorphism in the 15q11-q13 and neighboring region, we examined two dubious PWS patients in the molecular impairment type by STR gene linkage analysis. Then we draw a conclusion that they were patients of PWS which was caused by the deletion of paternal 15q11-q13. To check this, we have found that these patients only had a 174bp band by using MS-PCR analysis, which accorded with the diagnosic criteria for Prader-Willi syndrome.Studying the type of molecule defect and establishing the diagnostic method of PWS would be significant in the genetic consultation, estimation of recurrence ring, prenatal gene diagnosis of PWS in our country.