Novel mutations inTGM1andABCA12cause autosomal recessive congenital ichthyosis in five Saudi families
| Autor: | Rula Al Thuraya, Ola Khalifa, Haya Al-Dossari, Salma M. Wakil, Mohammed Al Owain, Yousef Binamer, Rawan Al-Humaidy, Josef Finsterer, Brian F. Meyer |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Ectropion Saudi Arabia Dermatology Consanguinity medicine.disease_cause 030207 dermatology & venereal diseases 03 medical and health sciences symbols.namesake 0302 clinical medicine INDEL Mutation Congenital ichthyosis Humans Medicine ABCA12 Sanger sequencing Genetics Mutation Transglutaminases biology business.industry Ichthyosis Genetic heterogeneity Homozygote medicine.disease Disease gene identification Pedigree 030104 developmental biology symbols biology.protein ATP-Binding Cassette Transporters Female business Ichthyosis Lamellar |
| Zdroj: | International Journal of Dermatology. 55:673-679 |
| ISSN: | 0011-9059 |
| DOI: | 10.1111/ijd.13279 |
| Popis: | Background Autosomal recessive congenital ichthyosis (ARCI) is a rare disorder of keratinization. Infants (10–15%) born with this condition are encapsulated in hyperkeratotic membrane covering the entire body and are called “collodion babies.” So far, mutations in nine different genes have been identified as causative and implicated in the pathogenesis of the clinically and genetically heterogeneous group of ARCI disorders. Among these, TGM1 is the gene most commonly mutated in ARCI. Methods We identified 11 patients from five consanguineous but unrelated families affected by ARCI. These patients manifested thick adherent polygonal large scales all over the body. All six patients with TGM1 mutations were born with collodion membrane and had ectropion and eclabium, while none of the patients with ABCA12 mutations had these features. Molecular investigations were performed using the combined approach of homozygosity mapping and Sanger sequencing. Results Here we report two novel mutations c.397_398insAGTATGAGTA (p.Tyr136Ter); c.977-978delCT (p.Ser326Cysfs*8) in TGM1 in three different, unrelated Saudi families and one novel mutation c.6900C>A (p.Phe2300Leu) and one reported mutation c.3470C>T (p.Ser1157Leu) in the ABCA12 gene in two unrelated Saudi families with ARCI. Conclusions The identification of these homozygous variants using combined approaches of homozygosity mapping with direct sequencing are the disease causing mutations in these families. Furthermore, these findings are essential for the genetic diagnostic and prognostic workup with ARCI in Saudi patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text