1.Genome-wide Copy Number Variations Analysis In 143 Patients With Unexplained Mental Retardsation Or Development Delay 2.Genetic Diagnosis And Formation Mechanism Analysis In A Patient With Pallister-Killian Syndrome

â… . Genome-wide Copy Number Variations Analysis in 143 Patients with Unexplained Mental Retardation or Development DelayBackground:Intellectual disability is also named mental retardation(MR). Defining features of MR include intellectual functioning level(IQ) below 70, significant limitations in adaptive skill areas, and the condition present from childhood(defined as age 18 or less). MR affects approximately 1-3% of general population. The diagnosis of development delay(DD) is always used in the patients during the preschool years, due to mainly manifesting psychomotor development delay, language development delay and so on. The etiology of MD/DD is complexity, genetic factors are found in approximately two-thirds of cases. Patients with MR/DD are bringing significant spiritual and financial burden for their families and the community. However, only about one half of the patients could be found definite etiological diagnosis, due to the complexity of the etiology. Traditional cytogenetic methods present apparent limitation in diagnosis of small aberration of chromosome. The advent of microarray technology has increased the resolution to an unprecedented level. Up to now, the microarray technology has been extensively used in etiology research of MR/DD in the United States and Europe, whereas, the application is vary limited in China.Objective:To explore the genetic etiology of 143 patients with unexplained mental retardation or development delay(MR/DD), and provide the theoretical basis for genetic counseling, risk assessment and prenatal diagnosis.Methods:Chose 143 patients with unexplained MR/DD, apply SNP array to detect the genome-wide copy number variations, in addition to FISH and bioinformatics analysis, explore the pathogenic copy number variations.Results:27 of 143 patients were found to carry the pathogenic copy number variations.Conclusions:Through genome-wide copy number variations analysis in 143 patients with unexplained MR/DD by SNP array, definite etiological diagnosis of 18.8%(27/143) patients were made. SNP array is a high-throughput technique for studying chromosome disease, it has revolutionized the etiological diagnosis for MR/DD. This study lays the foundation for discovering novel syndrome, and mapping and cloning new phenotype related genes.â…¡. Genetic Diagnosis and Formation Mechanism Analysis in A Patient with Pallister-Killian SyndromeBackground:Pallister-Killian syndrome(PKS) is a rare and sporadic genetic disorder due to tissue-limited mosaicism for supernumerary isochromosome 12p[i(12p)], which is usually absent or low-level of mosaicism in cultured lymphocytes but present in fibroblasts. PKS was first described in adults by Pallister in 1977, and later in children by Killian and Teschler-Nicola in 1981. The accurate incidence is unknown. It is clinically characterized by profound mental retardation, seizures, hypotonia, supernumerary nipples, pigmentary dysplasia, diaphragmatic hernia, "coarse" face, including prominent forehead with sparse anterior scalp hair, hypertelorism, short nose with anteverted nares, flat nasal bridge, long philtrum, cleft palate and short neck. Due to missed diagnosis of PKS using lymphocytes chromosome analysis, there is no reported cases in the mainland of China before.Objective:To make a definite genetic diagnosis for a patient with Pallister-Killian syndrome, and to analyze the formation mechanism of supernumerary i(12p).Methods:Use SNP array, karyotype analysis of fibroblasts and FISH to confirm a diagnosis of Pallister-Killian syndrome, and utilize Short Tandem Repeat Polymorphism(STRP) to analyze the formation mechanism of supernumerary i(12p).Results:The genome-wide copy number detection of peripheral blood lymphocytes showed a gain of the entire short arm of chromosome 12 in the patient, G-banding karyotyping of his skin fibroblasts indicated 46,XY[16]/47,XY,+i(12p)[84]. The supernumerary i(12p) was confirmed by FISH. STRP analysis suggested that D12S336 and D12S1617 were maternal heterodisomy, D12S345 was maternal isodisomy. D12S85, D12S78 and D12S86 on the 12q were normal biparental inheritance.Conclusions:Here we confirmed the first patient with Pallister-Killian syndrome in the mainland of China through SNP array, karyotype of fibroblasts and FISH. By molecular genetic analysis, suggesting that the maternal meiosisâ…¡sister chromatid non-disjunction was likely the first step in the formation of i(12p), followed by postzygotic mitotic centromeric misdivision.