Molecular Diagnose And Clinical Analysis Of A Family Of Short-Rib Thoracic Dysplasia Syndrome (Type Ⅲ)

【Backgroud】Fetal skeletal disorders are rare diseases,especially those complicating with short ribs,narrow thoracic ribs,and short long bones.It is always hard to clearly diagnose the fetal skeletal disorders prenatally simply by ultrasound.Because similar phenotype can be resulted from different genes and different diseases.Therefore,the prenatal diagnose the fetal skeletal disorders is difficult for clinical work.These years,as the prenatal diagnoses techniques progress,clinicians can better recognize theses disease from pathogenic mechanism and gene.【Objective】By studying the molecular diagnosis and clinical characteristics of the rare case of a family of short-rib thoracic dysplasia type Ⅲ and review the relative literatures,we systematically learn more about this kind of rare fetal skeletal diseases,including its characteristics,ultrasound diagnoses,prenatal gene diagnose and its progress.【Methods】Firstly,we retrospectively review and analyze a case of a family of rare fetal skeletal disorder: short-rib thoracic dysplasia type Ⅲ.Gather and analyze all the clinical information of the family,including molecular diagnose and clinical information including symptoms and ultrasound results,etc..Secondly,we search all the relative case reports and literatures with the languages restricted to Chinese and English.Systematically review and discuss the clinical characteristics,prenatal diagnoses,pathogenesis,gene detection and etc..【Results】1.Case report:The pregnant woman of the family has a history of pregnancy of fetal malformation with similar symptom,when she got pregnant for the third time,as the ultrasound suggested of clinical manifestations of short long bones,narrow thoracic ribs,FL/AC is 0.14,suggested of lethal skeletal disorders,so the doctor advised of induction.With the agreement of the patient,the fetal specimens were obtained through interventional prenatal diagnosis.Exome sequencing was performed on the blood and peripheral blood of the parents for Sanger verification.The result showed that the fetus(proband)had detected of a homozygous mutation in DYNC2H1 c.4267C>T(p.Arg 1423 Cys).This Variation have been reported and by Sanger verification,we found that the parents both carried with the same heterozygous mutation c.4267C>T in DYNC2H1.As a result,combined with the genotype,ultrasound and X-ray photography,this case is finally diagnosed of short rib-thoracic dysplasia type Ⅲ.2.Through the overall literature research,we found 2cases of Short-rib thoracic dysplasia type Ⅲ.2cases of Short-rib polydactyly syndrome,38 cases of Asphyxiating thoracic dystrophy of all the Chinese reports.In English reports,we found 2cases of Short-rib thoracic dysplasia type Ⅲ,12 cases of Short-rib polydactyly syndrome and because of some reason cannot sort out the cases of Asphyxiating thoracic dystrophy.【Conclusions】1.We report a family of Short-rib thoracic dysplasia type Ⅲ.Analysis including the clinical characteristic of the proband:short long bones,short ribs and narrow thoracic;the molecular diagnose that the gene screening of found the mutation of gene DYNC2H1 and it is a homozygous mutation.The proband’s parents were both carrier of heterozygous mutation of gene DYNC2H1 which is accord with the genetic law of AR.Therefore the proband is diagnosed of Short-rib thoracic dysplasia type Ⅲ.2.With the development of prenatal diagnosis technique like Exome sequencing helps the doctors to know the rare fetal skeletal diseases such as SRTD and it supply the clinicians earlier with more useful information to proceed genetic counseling and instruct the patients on the next pregnancy.