@article {647, title = {Inherited glomerular diseases in the gilded age of genomic advancements.}, journal = {Pediatr Nephrol}, volume = {35}, year = {2020}, month = {2020 06}, pages = {959-968}, abstract = {

The synchronized advent of high-throughput next-generation sequencing technology and knowledge of the human genome has rendered exponential contributions to our understanding of the pathophysiology of glomerular kidney diseases. A genetic diagnosis can now be made or confirmed in about two-thirds of the suspected inherited glomerular diseases. Next-generation sequencing is adept at identifying single nucleotide variations and small insertions or deletions that constitute majority of the disease-causing mutations. Description of the complete mutation spectrum in syndromic glomerulopathies may require the use of both sequencing and cytogenetic methods to detect large structural DNA variation in addition to single nucleotide changes. The enthusiastic application of genetic and genomic knowledge to inherited glomerular diseases has uncovered anticipated and unforeseen challenges mainly related to the biological interpretation of variants of uncertain significance and the limited benefit on clinical management for the individual patient when a diagnosis is obtained. To attain the ultimate goal of transforming clinical decision-making based on accurate genetic diagnosis using genomic information, these challenges need to be addressed. Till then, the glory of genomic medicine stands the test of time in this gilded age of genomic advancements.

}, keywords = {Adolescent, Age Factors, Branchio-Oto-Renal Syndrome, Child, Female, High-Throughput Nucleotide Sequencing, Humans, Infant, Kidney Failure, Chronic, Male, Middle Aged, Mutation, Pedigree, Polymorphism, Single Nucleotide, Renal Insufficiency, Chronic, Whole Exome Sequencing}, issn = {1432-198X}, doi = {10.1007/s00467-019-04266-y}, author = {Gulati, Ashima and Dahl, Neera and Tufro, Alda} } @article {367, title = {22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.}, journal = {Am J Med Genet A}, volume = {173}, year = {2017}, month = {2017 Apr}, pages = {1066-1070}, abstract = {

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject{\textquoteright}s phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH.

}, keywords = {46, XX Testicular Disorders of Sex Development, African Americans, Chromosome Duplication, Chromosomes, Human, Pair 22, Demyelinating Diseases, Hirschsprung Disease, Humans, Kidney Failure, Chronic, Male, Pelizaeus-Merzbacher Disease, SOXE Transcription Factors, Waardenburg Syndrome}, issn = {1552-4833}, doi = {10.1002/ajmg.a.38109}, author = {Falah, Nadia and Posey, Jennifer E and Thorson, Willa and Benke, Paul and Tekin, Mustafa and Tarshish, Brocha and Lupski, James R and Harel, Tamar} } @article {26, title = {Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation.}, journal = {BMC Nephrol}, volume = {17}, year = {2016}, month = {2016 Sep 06}, pages = {125}, abstract = {

BACKGROUND: Collapsing Glomerulopathy (CG), also known as the collapsing variant of Focal Segmental Glomerulosclerosis (FSGS), is distinct in both its clinical severity and its pathophysiologic characteristics from other forms of FSGS. This lesion occurs disproportionally in patients carrying two APOL1 risk alleles, and is the classic histologic lesion resulting from Human Immunodeficiency Virus (HIV) infection of podocytes. Other viral infections, including parvovirus B19, and drugs such as interferon that perturb the immune system, have also been associated with CG. Despite significant advances, explaining such genetic and immune/infectious associations with causative mechanisms and supporting evidence has proven challenging.

CASE PRESENTATION: We report the case of a healthy (HIV-negative) pregnant 36~year-old Caribbean-American woman who presented with nephrotic syndrome and fetal demise in the setting of acute parvovirus B19 infection. A series of three renal biopsies and rapid clinical course showed progression from significant podocyte injury with mild light microscopy findings to classic viral-associated CG to ESRD in less than 3~months. Genetic analysis revealed two APOL1 G1 risk alleles.

CONCLUSIONS: This is the first published case report of CG in the setting of acute parvovirus infection in a patient with two APOL1 risk allelles, and parvoviral proteins identified in renal epithelium on kidney biopsy. These findings support the causative role of parvovirus B19 infection in the development of CG on the background of APOL1 genetic risk.

}, keywords = {Acute Disease, Adult, Alleles, Apolipoprotein L1, Female, Glomerulosclerosis, Focal Segmental, Humans, Kidney Failure, Chronic, Parvoviridae Infections, Parvovirus B19, Human, Pregnancy, Pregnancy Complications, Infectious}, issn = {1471-2369}, doi = {10.1186/s12882-016-0330-7}, author = {Besse, Whitney and Mansour, Sherry and Jatwani, Karan and Nast, Cynthia C and Brewster, Ursula C} }