Clinical Manifestations And Gene Analysis Of Dyschondroplasia And Chromosome 22q11 Microdeletion Syndrome

Part Oneclinical manifestations and gene mutation analysis of dyschondroplasia familiesObjective:To screen the fibroblast growth factor receptor 3(FGFR3)gene sequence in thirteen dyschondroplasia children and their family members for searching the mutations,meanwhile to further validate the relationship between gene mutations and clinical phenotypes,and understand the pathogenesis of the diseases.Methods:1.Intravenous anticoagulant of the 13 patients who were diagnosed as dyschondroplasia and their family members was collected,use DNA extraction kit to extract genomic DNA.2.The sequence of exon 10 in mutation hot spot region of FGFR3 gene in13 probands was analyzed using polymerase chain reaction(PCR)and DNA sequencing technology to judge whether the 1138th nucleotide mutation existed which is known as the ACH mutation hot spot,reverse sequencing and repeat sequencing are used to to confirm the abnormal sequencing results and gene mutation.3.If the proband had the abnormal gene mutation mentioned above in exon 10 of FGFR3 gene,then his or her family members were immediately performed mutation analysis in the same site;If not,we analyze the sequence of exon 13 of FGFR3 gene in the probands and their family members use the above mentioned methods,to judge whether the 1620th nucleotide mutation existed which is known as the hot spot of HCH.Results:1.13 probands,including 8 males and 5 famales,had similar clinical characteristics:short stature,macrocephaly with frontal bossing,nasel bridge collapse,rhizomelic shortening of the limbs disproportionate with trunk,Lumbar vertebra protrusion and normal intelligence;X-ray examination revealed giant calvarium,shortning of long bones,vertebral body thickness decreased and contracted pelvis,etc.While one female patient had mild symptoms,and her mother had the same clinical manifestations.2.The c.1138G>A missense mutation in exon 10 was found in 8 probands who were diagnosed as achondroplasia(ACH),while this mutation was absent in their parents.3.The c.1620C>A missense mutation in exon 13 was found in one girl and her mother who both were diagnosed as hypochondroplasia(HCH)with mild symptoms,while this mutation was absent in her father and sister.4.Neither mutation mentioned above was found in the other 4 probands.Conclusions:1.c.1138G>A mutation in exon 10 of FGFR3 gene is the most common cause of ACH,c.1620C>A mutation in exon 13 leads to HCH,which is consistent with the previous reports both in China and abroad.2.Detecting the mutation in exon 10,exon 13 of FGFR3 gene,we can make the final diagnosis for most patients of ACH or HCH.However,it is necessary to perform the mutation screening on the other zones of FGFR3 gene and other related genes for a few cases.Part Twoclinical features and gene analysis of one patient with chromosome 22q11 Microdeletion SyndromeObjective:To detect genome-wide copy number variants(CNVs)in physical growth and mental retardation children through whole-genome microarray scanning technology to assist clinical diagnosis;Summarize clinical manifestations of 22q11 microdeletion syndrome and the diagnostic value of whole-genome microarray scanning technology.Methods:Describing the clinical manifestations of one patient who had unclear aetiology of physical growth and mental retardation.Recording his clinical characteristics and chromosome karyotype analysis,using whole-genome microarray scanning technology to detect CNVs and the results were validated by real-time fluorescence quantitative PCR technique(FQ-PCR),comprehensive analysis was made combined with literature review.Results:A male patient,8 years and 6 months old,112cm(<-3SD),15.5Kg(<-3SD).He had presented with severe mental retardation and special facial expressions:long face,ocular hypertelorism,flat genal,low nasel bridge,agenesis of alveolar bones and simple crease of the right palm.Chromosome karyotype analysis:46,XY;Whole-genome microarray scanning technology analysis prompted a 2.3 Mb deletion in 22 Chromosome(22q 11.2)(19,030,620-21,334,13 8)section,FQ-PCR confirmed this result.The patient was diagnosed as 22q11 Microdeletion Syndrome(22q11DS).Conclusions:1.Whole-genome microarray scanning technology can help to clear part of causes of children with physical growth and mental retardation,and may help to discover new pathogenic CNVs,which is beneficial for genetic counseling.2.The clinical manifestation of 22q11DS patients varies,some of the patients may not be typical,which should be take seriously.