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Molecular genetic study of acute intermittent porphyria in Russia: HMBS gene mutation spectrum and problem of penetrance
Author(s) -
Goncharova Maria,
Pshenichnikova Olesya,
Luchinina Yulia,
Pustovoit Yaroslav,
Karpova Irina,
Surin Vadim
Publication year - 2019
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13558
Subject(s) - acute intermittent porphyria , penetrance , genetics , exome sequencing , mutation , porphyria , gene , biology , medicine , phenotype , endocrinology
Acute intermittent porphyria (AIP) is the most common and severe form of porphyrias. This is a dominant inherited disorder with low penetrance, caused by mutations in gene coding hydroxymethylbilane synthase (HMBS). We present the results of our long‐term genetic study of AIP patients and their relatives (N = 153 and 302, respectively). We detected 88 HMBS gene mutations, 24 of which never described before. To identify additional factors conditioning AIP manifestation, we carried out whole exome sequencing on the group of AIP patients (N = 6). Mutation spectra of different patients virtually did not overlap. In 5 out of 6 patients, we found defects in genes regulating nervous system ( UNC13A, ALG8, FBXO38, AGRN , DOK7 , SCN4A ). As usually acute AIP attacks have various neurological symptoms, we proposed a hypothesis of possible contribution of mutations in such genes in AIP manifestation.