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HMBS Mutations in Chinese Patients with Acute Intermittent Porphyria
Author(s) -
Yang C.C.,
Kuo H.C.,
You H.L.,
Wang J.,
Huang C.C.,
Liu C.Y.,
Lan M.Y.,
Stephenson D. A.,
Lee M.J.
Publication year - 2008
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2008.00463.x
Subject(s) - missense mutation , acute intermittent porphyria , genetics , nonsense mutation , medicine , paresis , splice site mutation , endocrinology , compound heterozygosity , porphyria , allele , mutation , biology , exon , gene , surgery , alternative splicing
Summary Acute intermittent porphyria (AIP), an autosomal dominant disorder, is caused by partial deficiency of hydroxymethylbilane synthase (HMBS) affecting heme biosynthesis. Patients with AIP are characterized by recurrent abdominal pain, port‐wine urine, and motor paresis. The disease can be provoked by changes in hormone levels, drugs and fasting. Molecular analysis for twenty‐four unrelated Chinese AIP patients from Taiwan identified twenty‐five HMBS mutations. There were 10 missense (40%), four nonsense (16%), five frame‐shift (20%) and six splice site (24%) mutations. More than a half (15/25, 60%) of these mutations are predicted to produce a truncated protein. Four (c.33 + 5C>A, Arg26Cys, Arg26His, Arg325X) occurred more than once among the 24 families and one individual carried two mutations in the same allele, a missense (Gly221Asp) and a splice site mutation (c.652‐1G>A). Of the 25 mutations, eleven were novel (Arg149Pro, Gly218Arg, Asn322X, Gly221Asp, Pro313X, c.88‐4_‐16delAAGTCTCTACCCG , c.1008_1019delCAGCCTGGCCAA , c.113delT, c.88‐4_‐16delAAGTCTCTACCCGinsCA , c.160delA, c.902_909delTCCCTGCC ). No correlation between genetic defect and phenotype (both clinical and biochemical) was observed in this study.