Cholate-CoA ligase （,EEL） and bile acid-CoA： amino acid N-acyltransferase （BAAT） sequentially mediate bile-acid amidation. Defects can cause intrahepatic cholestasis. Distinction has required gene sequencing. We ...Cholate-CoA ligase （,EEL） and bile acid-CoA： amino acid N-acyltransferase （BAAT） sequentially mediate bile-acid amidation. Defects can cause intrahepatic cholestasis. Distinction has required gene sequencing. We assessed potential clinical utility of immunostaining of liver for CCL and BAAT. Using commercially available antibodies against BAAT and CCL, we immunostained liver from an infant with jaundice, deficiency of amidated bile acids, and transcription-terminating mutation in BAAT. CCL was normally expressed. BAAT expression was not de- tected. Immunostaining may facilitate diagnosis in bile- acid amidation defects.展开更多
Progressive familial intrahepatic cholestasis （PFIC） type 2 is caused by mutations in ABCB11, which encodes bile salt export pump （BSEP）. We report a Thai female infant who presented with progressive cholestatic j...Progressive familial intrahepatic cholestasis （PFIC） type 2 is caused by mutations in ABCB11, which encodes bile salt export pump （BSEP）. We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum y-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11, a four-nucleotide deletion in exon 3, c.90_93delGAAA, and a single-nucleotide insertion in exon 5, c.249_250insT, were identified, with confirmation in her parents. These mutations were predicted to lead to synthesis of truncated forms of BSEP. Immunostaining and mutation analysis thus established the diagnosis of PFIC type展开更多
基金Supported by Great Ormond Street Hospital Children’s Charity, to Clayton PTNational Institutes of HealthGrant R01 DK58214, to Bull LN
文摘Cholate-CoA ligase （,EEL） and bile acid-CoA： amino acid N-acyltransferase （BAAT） sequentially mediate bile-acid amidation. Defects can cause intrahepatic cholestasis. Distinction has required gene sequencing. We assessed potential clinical utility of immunostaining of liver for CCL and BAAT. Using commercially available antibodies against BAAT and CCL, we immunostained liver from an infant with jaundice, deficiency of amidated bile acids, and transcription-terminating mutation in BAAT. CCL was normally expressed. BAAT expression was not de- tected. Immunostaining may facilitate diagnosis in bile- acid amidation defects.
文摘Progressive familial intrahepatic cholestasis （PFIC） type 2 is caused by mutations in ABCB11, which encodes bile salt export pump （BSEP）. We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum y-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11, a four-nucleotide deletion in exon 3, c.90_93delGAAA, and a single-nucleotide insertion in exon 5, c.249_250insT, were identified, with confirmation in her parents. These mutations were predicted to lead to synthesis of truncated forms of BSEP. Immunostaining and mutation analysis thus established the diagnosis of PFIC type
