title: Genetic diagnosis in consanguineous families with kidney disease by homozygosity mapping coupled with whole-exome sequencing.
abstract: BACKGROUND
  Accurate diagnosis of the primary cause of an individual's kidney disease can be essential for proper management. Some kidney diseases have overlapping histopathologic features despite being caused by defects in different genes. In this report, we describe 2 consanguineous Saudi Arabian families in which individuals presented with kidney failure and mixed clinical and histologic features initially believed to be consistent with focal segmental glomerulosclerosis.
  
  
  METHODS
  Case series.
  
  
  METHODS
  We studied members of 2 apparently unrelated families from Saudi Arabia with kidney disease.
  
  
  METHODS
  Whole-genome single-nucleotide polymorphism analysis followed by targeted isolation and sequencing of exons using genomic DNA samples from affected members of these families, followed by additional focused genotyping and sequence analysis.
  
  
  RESULTS
  The 2 apparently unrelated families shared a region of homozygosity on chromosome 2q13. Exome sequence from affected individuals lacked sequence reads from the NPHP1 gene, which is located within this homozygous region. Additional polymerase chain reaction-based genotyping confirmed that affected individuals had NPHP1 deletions, rather than defects in a known focal segmental glomerulosclerosis-associated gene.
  
  
  CONCLUSIONS
  The methods used here may not result in a clear genetic diagnosis in many cases of apparent familial kidney disease.
  
  
  CONCLUSIONS
  This analysis shows the power of new high-throughput genotyping and sequencing technologies to aid in the rapid genetic diagnosis of individuals with an inherited form of kidney disease. We believe it is likely that such tools may become useful clinical genetic tools and alter the manner in which diagnoses are made in nephrology.
authors.affiliation: Stem Cell Therapy Program, King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Khaldoun I
authors.initials: KI
authors.lastname: Al-Romaih
authors.forename: Giulio
authors.initials: G
authors.lastname: Genovese
authors.forename: Hamad
authors.initials: H
authors.lastname: Al-Mojalli
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Othman
authors.forename: Hadeel
authors.initials: H
authors.lastname: Al-Manea
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Suleiman
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Jondubi
authors.forename: Nourah
authors.initials: N
authors.lastname: Atallah
authors.forename: Maha
authors.initials: M
authors.lastname: Al-Rodayyan
authors.forename: Astrid
authors.initials: A
authors.lastname: Weins
authors.forename: Martin R
authors.initials: MR
authors.lastname: Pollak
authors.forename: Chaker N
authors.initials: CN
authors.lastname: Adra
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003241:Consanguinity; D005260:Female; D006720:Homozygote; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017422:Sequence Analysis, DNA