The Clinical Research And Mutation Analysis Of The SMARCB1 Gene In A Rare Intraspinal Schwannomatosis Family

Objective:By collecting the clinical information and genetic test results of a rare intraspinal schwannomatosis family,the thesis deeply analyzes its clinical features,pathogenetic regularity and clinical outcome to provide clinical basis for etiology,diagnosis and prognosis of schwannomatosis and improve systematic understanding of the disease.Methods:The clinical information of the diseased individuals of this family was collected(the proband,brother,father),including a detailed medical history,operation history,pathologic results,imaging data,and so on.Relevant assessment was conducted at unaffected individuals and the causes of death and related diseases were investigated at the dead.The blood or saliva samples of whole family members were collected to extract DNA.Primers were designed for entire exons of SMARCB1 which was amplified by PCR,and the mutation of SMARCB1 gene was screened by Sanger sequencing.Results:It is confirmed that 3 people have been sickened in this family.The proband,a 30-year-old woman,had 5 times of operative history that removed 17 tumors;The brother of the proband,a 32-year-old man,had 4 times of operative history that removed 9 tumors;The father of the proband,a 59-year-old man,had 3 times of operative history that removed 10 tumors;All results of the postoperative histopathology of them were intraspinal schwannomatosis.The proband died because her condition deteriorated rapidly and appeared multiple lung metastases.Metastatic malignant peripheral nerve sheath tumor(MPNST)was confirmed by needle biopsy of lung lesions.The grandfather of the proband died at the age of 83 of cerebral hemorrhage.The grandmother of the proband died at the age of 83 of cardiopulmonary failure.The little sister-in-law of the proband died at the age of 22 of lung cancer.The second aunt of the proband had space-occupying lesions in lumbar spinal canal for many years,which confirmed by MRI and was suspected as schwannomatosis.The other family members are healthy.Using genetic testing in 25 people of three generations of this family,we found 8 people had a splice site mutation(c.1118+1G>A)that occurred between exon 8 and 9 of the SMARCB1 gene: male 2,female 6.The family denied the existence of consanguineous marriage.Conclusions:Familial schwannomatosis is very rare both at home and abroad and there is only one article reporting this disease at home before.The proband eventually died from metastatic MPNST which developed from schwannomatosis extremely rare.The germline mutation of SMARCB1 gene may be the main reason that lead to the occurrence of familial schwannomatosis and malignancy as MPNST.We found a splice site mutation(c.1118+1G>A)that occurred between exon 8 and 9 of the SMARCB1 gene of this family and there is only one article reporting this mutational pattern worldwide before.Currently,surgical resection is still the frist treatment option for schwannomatosis and MPNST.The results of this research could lay the foundation for the further study of schwannomatosis.