RESUMO
Xeroderma pigmentosum (XP) is a rare genodermatosis predisposing to skin cancers. Autoimmune diseases related to XP are rarely discussed in the literature. Type 1 diabetes (T1D) has been associated with other genodermatoses like Cockayne syndrome, but it has never been described in XP. In the present study, we report the rare occurrence of T1D in XP patients. Five XP patients belonging to 4 consanguineous families originating from different regions of Tunisia were investigated. Their ages ranged between 8 and 18 years. All the patients had a severe hypovitaminosis D. All the patients had positive GAD antibody levels, and 4 of them had familial history of other autoimmune diseases. The spectrum of XP was variable in all the patients, with dermatological and neurological symptoms, and the occurrence of some cancers. Various hypotheses have been proposed to explain this association, among of which we cite the role of immunomodulation and down-regulation of ATP-dependent DNA excision repair protein genes, implying that impaired DNA repair may contribute to the development of some autoimmune diseases. Vitamin D3 deficiency secondary to sun protective measures was found in all patients and thus may play a role in increasing T1D risk in these patients.
Assuntos
Diabetes Mellitus Tipo 1 , Xeroderma Pigmentoso , Trifosfato de Adenosina , Adolescente , Criança , Colecalciferol , DNA , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Humanos , Xeroderma Pigmentoso/complicações , Xeroderma Pigmentoso/genética , Xeroderma Pigmentoso/metabolismoRESUMO
The Androgen insensitivity syndrome (AIS) in its complete form (CAIS) is a disorder in abnormal male development characterized by a complete female phenotype in a 46,XY individual. The most frequent cause of this disorder is a hemizygous mutation in androgen receptor (AR) gene located inâ¯Xâ¯chromosome. The first aim of this study was to confirm the clinical diagnosis in a series of Tunisian patients with a typical phenotype of CAIS by molecular genetic analysis. The second aim was to determine the AR mutational profile in the local population. The entire coding region and the exon-intron junctions of the AR gene were sequenced in a series of ten patients. AR defects were found in nine patients. Despite the small number of cases, two of the nine identified mutations were novel. The first novel mutation was an 8-bp deletion in exon 1 (c.862_869del) resulting in a frameshift (p.A288Qfs*14). The second was a splice site mutation c.1885â¯+â¯1Gâ¯>â¯T (IVS3â¯+â¯1Gâ¯>â¯T). In this study, genetic testing has confirmed the diagnosis of most CAIS patients and has revealed two novel mechanisms responsible for the pathogenesis of AIS, as well as seven other reported mutations.
Assuntos
Síndrome de Resistência a Andrógenos/genética , Receptores Androgênicos/genética , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Mutação , Fenótipo , Tunísia , Adulto JovemRESUMO
OBJECTIVES: This study was aimed to investigate the association of the single nucleotide polymorphism of tumor necrosis factor receptor associated factor 6 (TRAF6), rs540386, with low bone mineral density (BMD) among patients with rheumatoid arthritis (RA). METHODS: TRAF6 rs540386 genotyping was performed by mutagenically separated PCR in a cohort of 188 (23 men, 165 women, median age, 56.2 years) adult RA patients and 224 age and gender-matched controls. BMD was measured using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy advance scans, GE Healthcare, USA). RESULTS: Among the RA patients, 64 (55 women, 9 men) had low BMD comprising of 57 patients with osteoporosis and 7 with osteopenia. Whereas TRAF6 rs540386 was not associated with RA susceptibility, it was however found to be a risk factor for reduced lumbar spine Z-score in the recessive model (OR = 3.34, 95% CI = (1.01-11.00), p = 0.038). This association was confirmed further in the multivariate logistic regression analysis taking into account several potential confounding factors (OR = 3.34 (1.01-11.00), p = 0.048). In addition, mean total femur Z-score was found to be reduced in TT patients when compared to CC + CT patients (- 1.30 ± 1.32 versus - 0.60 ± 1.05, p = 0.034). No association between TRAF6 rs540386 and local bone damage was observed. CONCLUSIONS: This study for the first time ever demonstrated an association between a genetic variant of TRAF6 and low BMD among patients with RA. Further investigations are needed to elucidate the exact role of this variant.