Detection Of ACAN Gene Mutation In A Patient With Dwarfism And Spondylometaphyseal Dysplasia And Analysis Of Clinical Factors Influencing Dwarfism

Part? : Molecular diagnosis and clinical analysis of Aggrecan mutation in a patient with spondylometaphyseal dysplasia and short statureObjective: To study the mutation of ACAN gene to provide the molecular biology basis for gene diagnosis and treatment of dwarfism.Subjects: The patient is a 13.5 years old girl and 88 cm,16 kg.The patient's height is obviously below the average height of-3 SD and is diagnosed of dwarfism.Her father is 167 cm tall and mother is 153 cm tall.Her sister is 9 years old and 135 cm tall.The patient is born with special face,short stature and relative macrocephaly.Physical examination: The patients has extremely short stature,relative macrocephaly,skeletal deformity,lbrachydactyly,chicken breast,the short fourth metacarpal,X-leg,normalintelligence,without other special symptom.Methods: The Agilent SureSelect method was used for exon capture and the Illuminated sequencing platform was used for high-pass sequencing.Sequencing data were analyzed by Next GENe @ software,then were mutated,sieved and interpreted by Ingenuity online software system.Candidate variants were verified by Sanger sequencing.Results: The hand radiograph shows 11 years old of bone age,decreasing bone density,irregular epiphyses,the short fourth metacarpal which is considered the developmental deformity.The growth hormone provocation is normal.The MRI of hypothalamusand pituitary is normal.Finally,the c.7339₇349del TGCGGAGAGCC p.C2447fs*17 homozygous mutations of ACAN was found,and the mutation was never found before.Predicted by Alamut functional software,the mutation may cause prematurely termination of amino acid translation or affect m RNA expression.So the mutation leads to disease,which is a "pathogenic" variant according to the ACMG mutation classification criteria.Conclusion: This mutation of ACAN gene is a newly discovered mutation.The clinical symptoms are consistent with spondylometaphyseal dysplasia.The ACAN mutation may be the cause of skeletal deformities and short stature in this patient.Genetic mutation screening helps to make a clear diagnosis of patients with obvious deformities of unknown etiology.Part ?: Analysis of the etiology of short stature and efficacy evaluation of rh GHObjective: To analyze the clinical data of short stature patients diagnosed and treated in our hospital and analyze the composition of different etiology.Evaluate the efficacy of rh GH and analyze the factors that influence its efficacy.Methods: Collect the data of patients with short stature diagnosed and treated by The First Affiliated Hospital of Soochow University from 2013 to 2017 and analyze their etiology.Observe the patients?including GHD,ISS,TS,CPP,etc.?,sustained subcutaneous injection with the human growth hormone.Evaluate the effect of rh GH and its influencing factors on the change of height SDS??Ht SDS?during rh GH treatment.Results: There were 259 short stature patients diagnosed and treated in our hospital,including 169 males and 90 females,with a male / female ratio of 1.88 / 1.Among them,there were 179 patients with GHD,accounting for 69.11%;69 patients were ISS,accounting for 26.64%;4 patients were constitutimal delay of puberty,accounting for 1.54%;3 patients were SGA,accounting for 1.16%;3 patients were TS,accounting for 1.16%;1 patient were Laron's syndrome,accounting for 0.39%.94 patients reached the height of 142.02 ± 13.51 / 142?132.9,150.98?cm after 6 months rh GH treatment from 137.01 ± 14.04 / 137.25?128,146.28?cm before treatment,the Ht SDS improved from-1.35 ± 1.7 /-1.42?-1.92,-0.20?to-0.97 ± 1.59 /-0.98?-1.56,0.10?.The treatment effect was evaluated by changing of Ht SDS.Analyzing the change of Ht SDS by non-parametric test samples?p <0.05?,rh GH benefit height linear growth.The factors associated with the effect of rh GH by nonparametric test were etiology?P <0.05?,initial height?rs =-0.464,p = 0.00?,initial body weight?rs=-0.352,p = 0.001?,age?sex?mid-parental height had no effect on the efficacy of rh GH.Multivariate linear regression analysis showed that the initial height is the independent determinant of rh GH efficacy?Beta=-0.415,P<0.05?.Conclusions: The etiology of short stature is complicated,GHD accounts the majority,followed by ISS and other reasons.The treatment of different causes of short stature are different.Pay close attention to the growth and development of children,strive to make early detection of short stature,early diagnosis,for the cause to be targeted treatment.The effect of rh GH on the linear growth of height is clear.The initial height can be used as one of the evaluation indicators of rh GH efficacy.