ABSTRACT
Objective To understand the clinical and molecular characteristics of children with Prader-Willi syndrome (PWS) in South China.Methods Clinical and molecular data of children diagnosed as PWS by Methylation-specific PCR(MS-PCR) and/or Array Comparative Genomic Hybridization(Array-CGH)in Guangzhou Women and Children's Medical Center from November 2012 to November 2014 were analyzed.Results A total of 27 children diagnosed as PWS were included in this study,including 21 cases diagnosed by Array Comparative Genomic Hybridization (Array-CGH) and 13 cases diagnosed by methylation-specific PC R (MS-PCR).Within the 27 cases,13 cases were male(48.1％) and 14 cases were female(51.9％).The age on diagnosis was from 16 days to 16 years old.MS-PCR was performed in 13 cases,7 cases of them also performed Array-CGH,both of them showed a 174 bp fragment from the methylated allele and a 100 bp fragment from the unmethylated allele.Array-CGH analysis was performed in 21 cases,paternal deletion in 18 cases and mean interstitial deletions measure (5.48 ± 0.51) Mb in size,paternal duplication in 2 cases,loss of heterozygosity measure approximately 79.58 Mb in 1 case.Eighteen simple chromosome deletion cases were divided into 6 Del Ⅰ and 12 Del Ⅱ according to the location of Array-CGH and query the database to DECIPHER(Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources).The major phenotype included central hypotonia and feeding difficulty in all cases (100.0％),hypogonadism in 25 cases (92.6％),weak crying in 22 cases(81.5％),and hypopigmentation in 22 cases(81.5％).Fourteen cases beyond 1 year old had varied degrees of development disability and behavioral and psychiatric disturbance:speech articulation defects in 13 cases(92.9％),hyperphagia and weight gain too fast in 13 cases(92.9％) when they were between 1 to 6 years old[(2.80 ± 1.32) years old],and obesity in 12 cases (85.7％).Conclusions For PWS children in South China,there is no statistically significant difference in the clinical manifestation between Del Ⅰ and Del Ⅱ.PWS children in South China have typical clinical characteristics,which can be used as a further screening indication to implement molecular diagnostics.
ABSTRACT
Lipodystrophies represent a heterogeneous group of diseases characterized by varying degrees of body fat loss and predisposition to insulin resistance and metabolic complications such as diabetes mellitus,hypertrigly-ceridemia and hepatic steatosis. The lipodystrophies can be divided into generalized,partial or local,depending on the degree and locality of the observable fat loss;moreover,the generalized and partial divisions can be partitioned further into congenital or acquired forms. Until now,11 genetic factors including AGPAT2,BSCL2,CAVI,PTRF,PPARG, LMNA,ZMPSTE24,AKT2,CIDEC,PLINI and WRN were reported to be involved in congenital lipodystrophies. The most prevalent subtype of acquired lipodystrophy currently occurs with prolonged duration of protease inhibitor - contai-ning,highly - active antiretroviral therapy in human immunodeficiency virus(HIV)- infected patients. Other types of acquired lipodystrophies are mainly autoimmune in origin and display complement abnormalities. The current manage-ment includes cosmetic surgery and early identification and treatment of metabolic and other complications with diet, exercise,hypoglycemic drugs,and lipid - lowering agents. Metreleptin treatment demonstrated remarkable clinical effect and good tolerance.