This study is focused on Utah pedigrees with Alport Syndrome. This study has been active for over 25 years. Dr. Gregory and his coworkers have defined the mode of inheritance of this hereditary nephropathy and have demonstrated clearly that the disorder is X-linked. This conclusion was confirmed by likelihood analysis and subsequently by demonstrating tht disease genes mapped to chromosome X in three families. Additional mutations have been characterized by Dr. Gregory's group and by others. Genetic linkage has been exploited extensively to establish linkage to type 4 collagen genes. An autosomal recessive form of Alport Syndrome was also identified and demonstrated to be linked to the COL4A3/4 locus and in a single family, dominant inheritance was found to be linked to the same locus. The investigators have now completely sequenced the COL4A5 gene and the adjacent untranslated sequences and have designed PCR primers permitting a multiplex PCR mutation screen for defects at this locus. To date, 114 separate mutations have been detected in the investigator's laboratory. There include three large deletions, one small deletion, 19 frame shift mutations, 48 missense mutations, 28 splice site mutations and 15 termination mutations. Missense mutations coding for the non-collagenous domain and adjacent portions of the collagenous domain were generally associated with milder clinical phenotypes than were missense mutations in the 5' half of the gene or with other types of mutations. Sever families with quite mild phenotypes associated with late-onset renal disease and relatively inapparent hearing loss have been associated with mutations of the 3' end of the gene. New pedigrees continue to be recruited for these studies in an effort to define phenotype-genotype correlations, and to identify critical regions of the type 4 collagen genes that effect the structure of the glomerulous and of the structures involved in sensorineural hearing loss.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
3M01RR000064-36S1
Application #
6419508
Study Section
Project Start
1999-12-01
Project End
2001-02-28
Budget Start
Budget End
Support Year
36
Fiscal Year
2001
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Di Fiore, Juliann M; Martin, Richard J; Li, Hong et al. (2017) Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort. J Pediatr 186:49-56.e1
Adams, Ted D; Davidson, Lance E; Litwin, Sheldon E et al. (2017) Weight and Metabolic Outcomes 12 Years after Gastric Bypass. N Engl J Med 377:1143-1155
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628
Archer, Stephanie Wilson; Carlo, Waldemar A; Truog, William E et al. (2016) Improving publication rates in a collaborative clinical trials research network. Semin Perinatol 40:410-417
Phelps, Dale L; Ward, Robert M; Williams, Rick L et al. (2016) Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. Pediatr Res 80:209-17
Harper, Lorie M; Mele, Lisa; Landon, Mark B et al. (2016) Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes. Obstet Gynecol 127:893-8
Adams, T D; Hammoud, A O; Davidson, L E et al. (2015) Maternal and neonatal outcomes for pregnancies before and after gastric bypass surgery. Int J Obes (Lond) 39:686-94
Foglia, Elizabeth E; Nolen, Tracy L; DeMauro, Sara B et al. (2015) Short-term Outcomes of Infants Enrolled in Randomized Clinical Trials vs Those Eligible but Not Enrolled. JAMA 313:2377-9
Bowles, Neil E; Jou, Chuanchau J; Arrington, Cammon B et al. (2015) Exome analysis of a family with Wolff-Parkinson-White syndrome identifies a novel disease locus. Am J Med Genet A 167A:2975-84

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