13 research outputs found
Identification of a Novel Intragenic Deletion of the PHKED1 Gene in a Patient with Autosomal Recessive Polycystic Kidney Disease
Background
Autosomal recessive polycystic kidney disease (ARPKD) is caused by
mutations in the PKHD1 gene. In the present study, we describe a severe
case of ARPKD carrying a point mutation and a novel four-exon deletion
of PKHD1 gene.
Materials and Methods
The PKHD1, PKD1 and PKD2 genes were analyzed using next-generation
sequencing, whereas the PKHD1 gene exon deletions/duplications were
screened using multiplex ligation-dependent probe amplification.
Results
The c.2279G>A (p.Arg760His) mutation and a deletion encompassing exons
24-27 of PKHD1 gene were detected in compound heterozygosity in the
affected neonate. The complete documentation of the genetic basis of the
disease offered the possibility of a targeted prenatal diagnosis in the
following pregnancy of the couple.
Conclusion
Given that the molecular analysis of ARPKD is mainly based on sequencing
techniques, the PKHD1 gene exon deletion/duplication screening should be
performed as a complementary assay in patients suspected to have ARPKD
in the absence of two pathogenic mutations
Association of the SHBG gene promoter polymorphism with early markers of atherosclerosis in apparently healthy women
Objective: Androgen may be detrimental in the development of
cardiovascular disease in women. We investigated possible associations
between the (TAAAA)n polymorphism of sex hormone binding globulin (SHBG)
gene promoter, which influences transcriptional efficiency of the SHBG
gene - and thus the tissue androgen availability - and early markers of
atherosclerosis in apparently healthy women.
Design and methods: In this prospective clinical study, 153 consecutive
women (mean age 43.9 +/- 9 years, 66 of whom postmenopausal, without
known diabetes, cardiovascular disease), visiting our internal medicine
outpatients were examined for unrecognised features of the metabolic
syndrome. Endothelium dependent vasodilatation (FMD) and intima media
thickness of the common carotid artery (IMT) were recorded. According to
the number of SHBG gene promoter repeats patients were classified as
short (<= 7), medium (=8) and long repeat (>= 9) allele groups.
Results: The (TAAAA) n repeat length was an independent predictor of FMD
in multivariate analysis (p < 0.03). FMD was positively correlated with
SHBG levels (p = 0.004). Women carriers of two long alleles had
increased IMT (p = 0.031) although this was not independent in the
multivariate analysis.
Conclusions: Longer (TAAAA)n repeats in the SHBG gene promoter are
associated with impaired FMD, which is an early marker of
atherosclerosis. As this polymorphism has been associated with a more
androgenic phenotype in women, this association may reflect the
life-long tissue exposure to higher free androgens and indirectly
supports the view that androgenic exposure may have adverse
cardiovascular effects in women. (C) 2011 Elsevier Ireland Ltd. All
rights reserved