Consultation with the specialist

Introduction The term cryptorchidism originates from the Greek kryptos (concealed) and orchis (testis). The definition of the term cryptorchidism is appropriate; not only is the testis concealed, but so is much information regarding this common condition. More than 200 years ago, John Hunter described descent of the testis during the last 3 months of gestation and reported that testes that remain in the abdomen are unhealthy and do not function well. He also discussed the possibilities of failure to descend causing testicular abnormality and testicular abnormalities causing failure to descend. Cryptorchidism represents the most common genital abnormality seen by pediatric urologists. The incidence is 1 in 125 boys. The incidence is much higher in premature infants (1 in 3), and the lower the birth weight, the greater the incidence of cryptorchidism. This condition is seen in approximately 1 in 30 full-term infants, but in many of them, the testicles will descend during the first few months of life. There is a higher incidence of cryptorchidism associated with many chromosomal and single gene defects as well as with multiple malformation syndromes. In addition, there is a higher incidence of cryptorchidism in the siblings and sons of those who have or had cryptorchidism. We will describe the anatomy of both the cryptorchid and retractile testis and discuss the embryology of testicular descent, with an emphasis on hormonal factors.

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Abstract 595: Genomic, Transcriptomic and MiRNomic Analysis of Triglyceride and Cholesterol Distribution into Lipoprotein Fractions in the Rat

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.595 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Miloslava Hodúlová

Keyword(s):

Genome Wide Association Study ◽

Recombinant Inbred Strain ◽

Cholesterol Biosynthesis ◽

Single Gene ◽

Male Rats ◽

Brown Norway ◽

Ldl Particles ◽

Genome Wide ◽

Definition Of ◽

Hepatic Transcriptome

Background: Dyslipidemia is central to the definition of metabolic syndrome (MS), one of most prevalent human diseases worldwide. We preformed genome-wide association study (GWAS) of triacylglycerols (TG) and cholesterol (C) distribution into lipoprotein fractions in the recombinant inbred strain panel PXO (segregating alleles of two MS models, SHR and PD strains, together with those of normolipidemic Brown Norway strain origin), followed by transcriptomic and miRNomic (microRNA profiling) analyses. Methods: We established morphometric and metabolic profile in adult male rats of 14 PXO strains and two progenitor strains (n=183) including glucose tolerance and TG and C concentrations in 20 lipoprotein fractions. GWAS utilizing >20,000 SNPs was performed using MapManager, the significance validated by 2000 permutations per trait. The hepatic transcriptome and miRNome profiles of the most contrasting strains were generated using Affymetrix GeneAtlas system followed by network analysis (Ingenuity Pathway Analysis). Results: We have identified 14 haplotype blocks showing suggestive or significant linkage to studied traits. Except for LDL-TG loci on chromosomes 3 and 12, PXO strains carrying the SHR allele displayed significantly higher values of the lipid linked traits, e.g. LDL-C (21.2±0.4 vs. 12.5±0.4 mg/dl in PXO strains with SHR allele vs. BXH2 allele). C concentrations in large, medium and very small LDL particles were significantly associated to a single gene ( Lrp1b ). Subsequent transcriptomic comparison of phenotypically most contrasting identified series of dysregulated metabolic and signaling pathways including cholesterol biosynthesis and the key upstream regulators such as HNF1 , HNF4 and PPARA . Conclusion: We identified several novel variants associated to TG and C concentrations in lipoprotein fractions together with their transcriptomic and biological network correlates.

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Genetic Disorders and Major Extracardiac Anomalies Associated With the Hypoplastic Left Heart Syndrome

PEDIATRICS ◽

10.1542/peds.82.5.698 ◽

1988 ◽

Vol 82 (5) ◽

pp. 698-706 ◽

Cited By ~ 1

Author(s):

Marvin Natowicz ◽

Jane Chatten ◽

Robert Clancy ◽

Katrina Conard ◽

Tracy Glauser ◽

...

Keyword(s):

Hypoplastic Left Heart Syndrome ◽

Chromosomal Abnormalities ◽

Genetic Disorders ◽

Genetic Disorder ◽

Single Gene ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Gene Defects ◽

Insulin Dependent Diabetic ◽

Left Heart Syndrome

All pediatric autopsies of patients with hypoplastic left heart syndrome seen during an 11-year interval were reviewed to determine the frequency of underlying chromosomal and single-gene defects and idiopathic major extracardiac anomalies associated with this common, lethal congenital heart abnormality. Of 83 patients identified, nine had underlying chromosomal abnormalities, four had single-gene defects, ten had one or more major extracardiac anomalies without an identifiable chromosomal or mendelian disorder, and two were infants of insulin-dependent diabetic mothers. Overall, 23 patients (28%) had a genetic disorder and/or major extracardiac anomaly. The substantial prevalence of genetic causes of and major extracardiac anomalies associated with hypoplastic left heart syndrome underscores the need for a detailed genetic evaluation for all patients with hypoplastic left heart syndrome.

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Multiple Malformation Syndromes in DSD

Disorders|Differences of Sex Development ◽

10.1007/978-981-13-7864-5_10 ◽

2020 ◽

pp. 123-131

Author(s):

Aurore Bouty ◽

John M. Hutson

Keyword(s):

Multiple Malformation ◽

Malformation Syndromes

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ESHRE PGT Consortium good practice recommendations for the organisation of PGT†

Human Reproduction Open ◽

10.1093/hropen/hoaa021 ◽

2020 ◽

Vol 2020 (3) ◽

Cited By ~ 8

Author(s):

Filipa Carvalho ◽

Edith Coonen ◽

Veerle Goossens ◽

Georgia Kokkali ◽

Carmen Rubio ◽

...

Keyword(s):

Best Practice ◽

Single Gene ◽

Good Practice ◽

Diagnostic Testing ◽

Genetic Diagnosis ◽

Information Provision ◽

Embryo Biopsy ◽

Preimplantation Genetic Testing ◽

Gene Defects

Abstract The field of preimplantation genetic testing (PGT) is evolving fast, and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for preimplantation genetic diagnosis, published in 2005 and 2011, are considered outdated and the development of new papers outlining recommendations for good practice in PGT was necessary. The current updated version of the recommendations for good practice is, similar to the 2011 version, split into four documents, one of which covers the organisation of a PGT centre. The other documents focus on the different technical aspects of embryo biopsy, PGT for monogenic/single-gene defects (PGT-M) and PGT for chromosomal structural rearrangements/aneuploidies (PGT-SR/PGT-A). The current document outlines the steps prior to starting a PGT cycle, with details on patient inclusion and exclusion, and counselling and information provision. Also, recommendations are provided on the follow-up of PGT pregnancies and babies. Finally, some further recommendations are made on the practical organisation of an IVF/PGT centre, including basic requirements, transport PGT and quality management. This document, together with the documents on embryo biopsy, PGT-M and PGT-SR/PGT-A, should assist everyone interested in PGT in developing the best laboratory and clinical practice possible.

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GENETICS IN ENDOCRINOLOGY: Genetic forms of severe insulin resistance: what endocrinologists should know

Acta Endocrinologica ◽

10.1530/eje-13-0327 ◽

2013 ◽

Vol 169 (4) ◽

pp. R71-R80 ◽

Cited By ~ 22

Author(s):

Victoria E R Parker ◽

Robert K Semple

Keyword(s):

Insulin Resistance ◽

Insulin Signalling ◽

Polycystic Ovary ◽

Single Gene ◽

Clinical Syndrome ◽

Glucose Lowering ◽

Severe Insulin Resistance ◽

Gene Defects ◽

Lowering Activity

‘Insulin resistance’ (IR) is a widely used clinical term. It is usually defined as a state characterised by reduced glucose-lowering activity of insulin, but it is also sometimes used as a shorthand label for a clinical syndrome encompassing major pathologies such as type 2 diabetes, polycystic ovary syndrome, fatty liver disease and atherosclerosis. Nevertheless, the precise cellular origins of IR, the causal links among these phenomena and the mechanisms underlying them remain poorly understood or contentious. Prevalent IR usually results from a genetic predisposition interacting with acquired obesity; however, even in some lean individuals, very severe degrees of IR can be observed. It is important to identify these people as they often harbour identifiable single-gene defects and they may benefit from molecular diagnosis, genetic counselling and sometimes tailored therapies. Observation of people with known single-gene defects also offers the opportunity to make inferences about the mechanistic links between IR and common pathologies. Herein, we summarise the currently known monogenic forms of severe IR, with an emphasis on the practical aspects of their recognition, diagnosis and management. In particular, we draw distinctions among the biochemical subphenotypes of IR that arise from primary adipose tissue dysfunction or from primary insulin signalling defects and discuss the implications of this dichotomy for management.

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Diabetes Associated with Single Gene Defects

10.1159/isbn.978-3-318-06025-6 ◽

2017 ◽

Keyword(s):

Single Gene ◽

Gene Defects

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Contributions of Rare Gene Variants to Familial and Sporadic FSGS

Journal of the American Society of Nephrology ◽

10.1681/asn.2019020152 ◽

2019 ◽

Vol 30 (9) ◽

pp. 1625-1640 ◽

Cited By ~ 12

Author(s):

Minxian Wang ◽

Justin Chun ◽

Giulio Genovese ◽

Andrea U. Knob ◽

Ava Benjamin ◽

...

Keyword(s):

Rare Variants ◽

Single Gene ◽

Genetic Diagnosis ◽

Unrelated Family ◽

The Past ◽

New Genes ◽

Rare Gene ◽

Gene Defects ◽

Disease Associated Genes ◽

Burden Tests

BackgroundOver the past two decades, the importance of genetic factors in the development of FSGS has become increasingly clear. However, despite many known monogenic causes of FSGS, single gene defects explain only 30% of cases.MethodsTo investigate mutations underlying FSGS, we sequenced 662 whole exomes from individuals with sporadic or familial FSGS. After quality control, we analyzed the exome data from 363 unrelated family units with sporadic or familial FSGS and compared this to data from 363 ancestry-matched controls. We used rare variant burden tests to evaluate known disease-associated genes and potential new genes.ResultsWe validated several FSGS-associated genes that show a marked enrichment of deleterious rare variants among the cases. However, for some genes previously reported as FSGS related, we identified rare variants at similar or higher frequencies in controls. After excluding such genes, 122 of 363 cases (33.6%) had rare variants in known disease-associated genes, but 30 of 363 controls (8.3%) also harbored rare variants that would be classified as “causal” if detected in cases; applying American College of Medical Genetics filtering guidelines (to reduce the rate of false-positive claims that a variant is disease related) yielded rates of 24.2% in cases and 5.5% in controls. Highly ranked new genes include SCAF1, SETD2, and LY9. Network analysis showed that top-ranked new genes were located closer than a random set of genes to known FSGS genes.ConclusionsAlthough our analysis validated many known FSGS-causing genes, we detected a nontrivial number of purported “disease-causing” variants in controls, implying that filtering is inadequate to allow clinical diagnosis and decision making. Genetic diagnosis in patients with FSGS is complicated by the nontrivial rate of variants in known FSGS genes among people without kidney disease.

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