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Novel mutations in the genes TGM 1 and ALOXE 3 underlying autosomal recessive congenital ichthyosis
Author(s) -
Ullah Rahim,
Ansar Muhammad,
Durrani Zaka Ullah,
Lee Kwanghyuk,
SantosCortez Regie Lyn P.,
Muhammad Dost,
Ali Mahboob,
Zia Muhammad,
Ayub Muhammad,
Khan Suliman,
Smith Josh D.,
Nickerson Deborah A.,
Shendure Jay,
Bamshad Michael,
Leal Suzanne M.,
Ahmad Wasim
Publication year - 2016
Publication title -
international journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 93
eISSN - 1365-4632
pISSN - 0011-9059
DOI - 10.1111/ijd.12950
Subject(s) - genetics , congenital ichthyosis , missense mutation , ichthyosis , genetic linkage , biology , gene , nonsense mutation , disease gene identification , mutation , exome sequencing
Background Ichthyoses are clinically characterized by scaling or hyperkeratosis of the skin or both. It can be an isolated condition limited to the skin or appear secondarily with involvement of other cutaneous or systemic abnormalities. Methods The present study investigated clinical and molecular characterization of three consanguineous families (A, B, C) segregating two different forms of autosomal recessive congenital ichthyosis ( ARCI ). Linkage in three consanguineous families (A, B, C) segregating two different forms of ARCI was searched by typing microsatellite and single nucleotide polymorphism marker analysis. Sequencing of the two genes TGM 1 and ALOXE 3 was performed by the dideoxy chain termination method. Results Genome‐wide linkage analysis established linkage in family A to TGM 1 gene on chromosome 14q11 and in families B and C to ALOXE 3 gene on chromosome 17p13. Subsequently, sequencing of these genes using samples from affected family members led to the identification of three novel mutations: a missense variant p.Trp455Arg in TGM 1 (family A); a nonsense variant p.Arg140* in ALOXE 3 (family B); and a complex rearrangement in ALOXE 3 (family C). Conclusion The present study further extends the spectrum of mutations in the two genes involved in causing ARCI . Characterizing the clinical spectrum resulting from mutations in the TGM 1 and ALOXE 3 genes will improve diagnosis and may direct clinical care of the family members.