Erratum: The genomic architecture of NLRP7 is Alu rich and predisposes to disease-associated large deletions

NLRP7 is a major gene responsible for recurrent hydatidiform moles. Here, we report 11 novel NLRP7 protein truncating variants, of which five deletions of more than 1-kb. We analyzed the transcriptional consequences of four variants. We demonstrate that one large homozygous deletion removes NLRP7 transcription start site and results in the complete absence of its transcripts in a patient in good health besides her reproductive problem. This observation strengthens existing data on the requirement of NLRP7 only for female reproduction. We show that two other variants affecting the splice acceptor of exon 6 lead to its in-frame skipping while another variant affecting the splice donor site of exon 9 leads to an in-frame insertion of 54 amino acids. Our characterization of the deletion breakpoints demonstrated that most of the breakpoints occurred within Alu repeats and the deletions were most likely mediated by microhomology events. Our data define a hotspot of Alu instability and deletions in intron 5 with six different breakpoints and rearrangements. Analysis of NLRP7 genomic sequences for repetitive elements demonstrated that Alu repeats represent 48% of its intronic sequences and these repeats seem to have been inserted into the common NLRP2/7 primate ancestor before its duplication into two genes

Association of anthropometric, androgenic and insulin-related features with polymorphisms in exon 8 of SHBG gene in women with polycystic ovary syndrome

WOS: 000316925400020PubMed ID: 23305451Objective: Sex hormone binding globulin (SHBG) levels are often low in women with polycystic ovary syndrome (PCOS). In addition to metabolic and nutritional factors, SHBG levels are determined by genetic polymorphisms in SHBG gene. The aim of this study was to investigate the association of polymorphisms in exon 8 of SHBG gene with anthropometric and biochemical features of women with PCOS. Design: Prospective, observational study. Patients: One hundred and ninety-four women with PCOS. Main outcome measure(s): Genotype analysis of exon 8 in SHBG gene was performed. Serum SHBG, total testosterone, free testosterone, 17-alpha-hydroxyprogesterone, TSH, PRL, glucose and insulin levels were determined. Main finding(s): Single nucleotide polymorphism (SNP) E326K located at codon 326 in exon 8 of SHBG gene was identified. Serum SHBG levels decreased significantly with increasing copy number of the variant allele for SNP E326K after adjustment for BMI, androgenic and insulin-related traits. Genotype analysis also revealed SNP, rs6259, located at codon 327 in exon 8 of SHBG gene, which is not associated with SHBG levels. Conclusion: SNP, E326K, in exon 8 of SHBG gene may influence the metabolism of SHBG independently of BMI, androgenic and insulin-related features in women with PCOS

Prenatal diagnosis of Comel-Netherton syndrome with PGD, case report and review article

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Introduction Comel-Netherton syndrome (C-NS) is an autosomal recessive disorder of the skin, hair and immune system first reported by Comel in 1949 and Netherton in 1958 (1, 2). This syndrome presents at or soon after birth with generalized erythroderma, scaling, and/or continuous peeling of the skin resembling nonbulloous congenital ichthyosiform erythroderma or peeling skin syndrome. In the neonatal period, 20% of the babies suffer from hypernatremic dehydration, electrolyte imbalances, perturbed thermoregulation, failure to thrive and recurrent infections which may result in neonatal demise [3–5]. The skin lesions are often pruritic, resemble atopic eczema, and show an unstable, undulating course. They are usually accompanied by hair shaft abnormalities that develop during early childhood and may result in diffuse alopecia. The hallmark of C-NS is trichorrhexis invaginata (bamboo hair), but other abnormalities, including pili torti (twisted hair) and trichorrhexis nodosa (hair of varying diameter) have been observed. Markedly elevated IgE levels, allergic reactions to food and common antigens, malnutrition, and increased susceptibility to skin, respiratory tract or systemic infections are also characteristic [6, 7]. There are nearly 150–160 cases of C-NS reported in the literature, its incidence might be 1/200.000 [6] due to challenging diagnostic problems during infancy and early childhood. This syndrome has overlapping features with atopic dermatitis and other recessive ichthyosis. Most patients with C-NS are sporadic cases however, there are reports of affected siblings and of consanguinity in about 10% of the families with C-NS which is common in autosomal recessive inheritance [8–10]. In this study, we present two consanguineous Turkish families (two sisters married with two brothers) of prenatal diagnosis of Netherton syndrome and successful intracytoplasmic sperm injection (ICSI) pregnancies using PGD and a review of literature. To our knowledge, this is the first report of PGD and ICSI in Comel-Netherton syndrom

The genomic architecture of NLRP7 is Alu rich and predisposes to disease-associated large deletions

WOS: 000384088000010PubMed ID: 26956250NLRP7 is a major gene responsible for recurrent hydatidiform moles. Here, we report 11 novel NLRP7 protein truncating variants, of which five deletions of more than 1-kb. We analyzed the transcriptional consequences of four variants. We demonstrate that one large homozygous deletion removes NLRP7 transcription start site and results in the complete absence of its transcripts in a patient in good health besides her reproductive problem. This observation strengthens existing data on the requirement of NLRP7 only for female reproduction. We show that two other variants affecting the splice acceptor of exon 6 lead to its in-frame skipping while another variant affecting the splice donor site of exon 9 leads to an in-frame insertion of 54 amino acids. Our characterization of the deletion breakpoints demonstrated that most of the breakpoints occurred within Alu repeats and the deletions were most likely mediated by microhomology events. Our data define a hotspot of Alu instability and deletions in intron 5 with six different breakpoints and rearrangements. Analysis of NLRP7 genomic sequences for repetitive elements demonstrated that Alu repeats represent 48% of its intronic sequences and these repeats seem to have been inserted into the common NLRP2/7 primate ancestor before its duplication into two genes.Max E. Binz Fellowship from the McGill University Faculty of Medicine; Canadian Institute of Health ResearchCanadian Institutes of Health Research (CIHR) [MOP-86546, PPP-122897]We thank the patients and their family for their cooperation. The authors wish to acknowledge the use of the Sequencing platform of the McGill University and Genome Quebec Innovation Centre. NMPN was supported by a Max E. Binz Fellowship from the McGill University Faculty of Medicine. The study was supported by the Canadian Institute of Health Research grants, MOP-86546 and PPP-122897, to RS

The genomic architecture of NLRP7 is Alu rich and predisposes to disease-associated large deletions

NLRP7 is a major gene responsible for recurrent hydatidiform moles. Here, we report 11 novel NLRP7 protein truncating variants, of which five deletions of more than 1-kb. We analyzed the transcriptional consequences of four variants. We demonstrate that one large homozygous deletion removes NLRP7 transcription start site and results in the complete absence of its transcripts in a patient in good health besides her reproductive problem. This observation strengthens existing data on the requirement of NLRP7 only for female reproduction. We show that two other variants affecting the splice acceptor of exon 6 lead to its in-frame skipping while another variant affecting the splice donor site of exon 9 leads to an in-frame insertion of 54 amino acids. Our characterization of the deletion breakpoints demonstrated that most of the breakpoints occurred within Alu repeats and the deletions were most likely mediated by microhomology events. Our data define a hotspot of Alu instability and deletions in intron 5 with six different breakpoints and rearrangements. Analysis of NLRP7 genomic sequences for repetitive elements demonstrated that Alu repeats represent 48% of its intronic sequences and these repeats seem to have been inserted into the common NLRP2/7 primate ancestor before its duplication into two genes