المؤلفون: Ennouri, Mariem, Zimmer, Andreas D., Bahloul, Emna, Chaabouni, Rim, Marrakchi, Slaheddine, Turki, Hamida, Fakhfakh, Faiza, Bougacha-Elleuch, Noura, Fischer, Judith

المصدر: BMC Medical Genomics ; volume 15, issue 1 ; ISSN 1755-8794

مصطلحات موضوعية: Genetics (clinical), Genetics

الوصف: Background Ichthyosis is a heterogeneous group of Mendelian cornification disorders that includes syndromic and non-syndromic forms. Autosomal Recessive Congenital Ichthyosis (ARCI) and Ichthyosis Linearis Circumflexa (ILC) belong to non-syndromic forms. Syndromic ichthyosis is rather a large group of heterogeneous diseases. Overlapping phenotypes and genotypes between these disorders is a major characteristic. Therefore, determining the specific genetic background for each form would be necessary. Methods A total of 11 Tunisian patients with non-syndromic (8 with ARCI and 2 with ILC) and autosomal syndromic ichthyosis (1 patient) were screened by a custom Agilent HaloPlex multi-gene panel and the segregation of causative mutations were analyzed in available family members. Results Clinical and molecular characterization, leading to genotype–phenotype correlation in 11 Tunisian patients was carried out. Overall, we identified 8 mutations in 5 genes. Thus, in patients with ARCI, we identified a novel (c.118T > C in NIPAL4 ) and 4 already reported mutations (c.534A > C in NIPAL4 ; c.788G > A and c.1042C > T in TGM1 and c.844C > T in CYP4F22 ). Yellowish severe keratoderma was found to be associated with NIPAL4 variations and brachydactyly to TGM1 mutations. Two novel variations (c.5898G > C and c.2855A > G in ABCA12 ) seemed to be features of ILC. Delexon13 in CERS3 was reported in a patient with syndromic ichthyosis. Conclusions Our study further extends the spectrum of mutations involved in ichthyosis as well as clinical features that could help directing genetic investigation.

الإتاحة: https://doi.org/10.1186/s12920-021-01154-zTest

المؤلفون: Ballin, Nadja, Hotz, Alrun, Bourrat, Emmanuelle, Küsel, Julia, Oji, Vinzenz, Bouadjar, Bakar, Brognoli, Davide, Hickman, Geoffroy, Heinz, Lisa, Vabres, Pierre, Marrakchi, Slaheddine, Leclerc‐Mercier, Stéphanie, Irvine, Alan, Tadini, Gianluca, Hamm, Henning, Has, Cristina, Blume‐Peytavi, Ulrike, Mitter, Diana, Reitenbach, Marina, Hausser, Ingrid, Zimmer, Andreas D., Alter, Svenja, Fischer, Judith

مصطلحات موضوعية: Genetics(clinical), Genetics

الوصف: n/a

العلاقة: url:https://www.openaccessrepository.it/communities/itmirrorTest; https://www.openaccessrepository.it/record/30958Test

الإتاحة: https://doi.org/10.1002/humu.23883Test
https://www.openaccessrepository.it/record/30958Test

المؤلفون: Louhichi, Nacim, Hadjsalem, Ikhlass, Marrakchi, Slaheddine, Trabelsi, Fatma, Masmoudi, Abderrahmen, Turki, Hamida, Fakhfakh, Faiza

المصدر: Molecular Biology Reports ; volume 40, issue 3, page 2527-2532 ; ISSN 0301-4851 1573-4978

مصطلحات موضوعية: Genetics, Molecular Biology, General Medicine

الإتاحة: https://doi.org/10.1007/s11033-012-2333-1Test

المؤلفون: Radner, Franz P. W.¹, Marrakchi, Slaheddine², Kirchmeier, Peter^1,3, Kim, Gwang-Jin^1,3, Ribierre, Florence⁴, Kamoun, Bourane⁵, Abid, Leila⁶, Leipoldt, Michael¹, Turki, Hamida², Schempp, Werner¹, Heilig, Roland⁷, Lathrop, Mark^4,8,9, Fischer, Judith^1,4 judith.fischer@uniklinik-freiburg.de

المصدر: PLoS Genetics. Jun2013, Vol. 9 Issue 6, p1-11. 11p.

مصطلحات موضوعية: *ICHTHYOSIS, *GENETIC disorders, *RNA, *FUNCTIONAL analysis, *WEILL-Marchesani syndrome

مستخلص: Autosomal recessive congenital ichthyosis (ARCI) is a rare genetic disorder of the skin characterized by abnormal desquamation over the whole body. In this study we report four patients from three consanguineous Tunisian families with skin, eye, heart, and skeletal anomalies, who harbor a homozygous contiguous gene deletion syndrome on chromosome 15q26.3. Genome-wide SNP-genotyping revealed a homozygous region in all affected individuals, including the same microdeletion that partially affects two coding genes (ADAMTS17, CERS3) and abolishes a sequence for a long non-coding RNA (FLJ42289). Whereas mutations in ADAMTS17 have recently been identified in autosomal recessive Weill-Marchesani-like syndrome in humans and dogs presenting with ophthalmologic, cardiac, and skeletal abnormalities, no disease associations have been described for CERS3 (ceramide synthase 3) and FLJ42289 so far. However, analysis of additional patients with non-syndromic ARCI revealed a splice site mutation in CERS3 indicating that a defect in ceramide synthesis is causative for the present skin phenotype of our patients. Functional analysis of patient skin and in vitro differentiated keratinocytes demonstrated that mutations in CERS3 lead to a disturbed sphingolipid profile with reduced levels of epidermis-specific very long-chain ceramides that interferes with epidermal differentiation. Taken together, these data present a novel pathway involved in ARCI development and, moreover, provide the first evidence that CERS3 plays an essential role in human sphingolipid metabolism for the maintenance of epidermal lipid homeostasis. [ABSTRACT FROM AUTHOR]