Nonsense variant of ATP8B1 gene in heterozygosis and benign recurrent intrahepatic cholestasis: A case report and review of literature

BACKGROUND Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters.Herein,we firstly provide the evidence that a nonsense variant of ATP8B1 gene(c.1558A>T)in heterozygous form is involved in BRIC pathogenesis.CASE SUMMARY A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase.Acute and chronic liver diseases with viral,metabolic and autoimmune etiology were excluded.Normal intra/extra-hepatic bile ducts were demonstrated by magnetic resonance.Liver biopsy showed:Cholestasis in the centrilobular and intermediate zones with bile plugs and intra-hepatocyte pigment,Kupffer’s cell activation/hyperplasia and preserved biliary ducts.Being satisfied benign recurrent intrahepatic cholestasis diagnostic criteria,ATP8B1 and ABCB11 gene analysis was performed.Surprisingly,we found a novel nonsense variant of ATP8B1 gene(c.1558A>T)in heterozygosis.The variant was confirmed by Sanger sequencing following a standard protocol and tested for familial segregation,showing a maternal inheritance.Immunohistochemistry confirmed a significant reduction of mutated gene related protein(familial intrahepatic cholestasis 1).The patient was treated with ursodeoxycholic acid 15 mg/kg per day and colestyramine 8 g daily with total bilirubin decrease and normalization at the 6th and 12th mo.CONCLUSION A genetic abnormality,different from those already known,could be involved in familial intrahepatic cholestatic disorders and/or pro-cholestatic genetic predisposition,thus encouraging further mutation detection in this field.

Pseudoileus caused by primary visceral myopathy in a Han Chinese patient with a rare MYH11 mutation:A case report

BACKGROUND Chronic intestinal pseudo-obstruction(CIPO)is a syndrome of intestinal motor dysfunction caused by intestinal nerve,muscle,and/or Cajal stromal cell lesions.CIPO is a serious category of gastrointestinal dynamic dysfunction,which can eventually lead to the death of patients with intestinal failure.Due to considerable phenotypic heterogeneity,the estimated incidence of CIPO is 1/476190 and 1/416666 in men and women,respectively.According to the etiology,CIPO can be divided into idiopathic and secondary,of which the latter is the most common,often secondary to tumor,virus infection,connective tissue disease,neurological diseases,and endocrine diseases.Idiopathic CIPO in the intestinal tract is divided into visceral myopathy,neuropathy,and stromal cell lesions according to the location.Surgery is usually not recommended for CIPO,because it often does not benefit patients with CIPO,and postoperative intestinal obstruction is likely to occur,which may even worsen the condition.CASE SUMMARY Here,we describe the case of a 43-year-old male Han Chinese patient with a 15-year history of recurrent abdominal distention with no clear cause.The results of physical,biochemical,and other relevant examinations showed no clear abnormalities.Contrast-enhanced computed tomography(CT)indicated a large duodenum,clear expansion of the intestinal lumen,and CIPO.Whole exome sequencing(WES)of the patient and his mother confirmed the diagnosis of primary familial visceral myopathy type 2 chronic pseudoileus with a rare heterozygous gene mutation in MYH11.This is the second reported case of CIPO with a heterozygous MYH11[NM_001040113.1:c.5819delC(p.Pro1940Hisfs*91)]mutation.CONCLUSION This case report indicates that physicians can perform routine clinical examinations,CT,and WES to achieve a diagnosis and treatment of CIPO in early disease stages.

Factor V Leiden mutation in one family of Chinese origin

目的 研究中国人FVLeiden基因突变引起的抗活化蛋白C现象 (APCR)。方法 采用APTT±APC方法、多聚酶链反应 (PCR)、MnLI限制性内切酶分析 ,序列特异性引物 (PCR SSP)和DNA测序方法 ,对中国汉族 30例“正常”无关个体和 2 0例血栓性疾病患者进行APCR测定和FVLeiden基因突变分析。结果 发现一例正常人抗APC敏感值比值 (APC SR)明显减低 (0 8) ,并确诊为FVLeiden基因 (Arg50 6 Gln)突变杂合子 ,其叔祖父、父亲、弟弟和儿子同样确定为FVLeiden基因杂合子 ;有 3例血栓性疾病患者APC SR低于正常 ,但均无FVLeiden基因突变。结论 这是在国内发现的首例四代FVLeiden突变所致的APCR现象的家系。中国人血栓症中APCR的产生是否导致其它未知的基因缺陷 ,尚待进一步研究。