Alternative titles; symbols
SNOMEDCT: 236419006; ORPHA: 88659;
Cytogenetic location: 1q21 Genomic coordinates (GRCh38): 1:143,200,001-155,100,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q21 | Nephropathy-hypertension | 161900 | Autosomal dominant | 2 |
Richmond et al. (1981) reported an autosomal dominant nephropathy in which morphology was primarily interstitial, with secondary glomerular atrophy. Renal failure was documented in 5 females and 2 males. In addition, 2 males and 1 female were thought to have died in renal failure, and 4 other males and 1 female were known to be affected. All patients presented as adults with hypertension and proteinuria, usually of mild degree. Rheumatoid arthritis was present in several members of the kindred, including some persons without nephritis; in doubly affected persons, it appeared to bear no temporal relationship to the renal disease. None of the affected persons had macroscopic hematuria and only 2 had microscopic hematuria. Extensive renal damage was present in 1 person despite good function.
Cohn et al. (2000) reported a large Israeli family of Iraqi Jewish origin with an autosomal dominant form of adult-onset nephropathy and hypertension. There were 14 affected individuals spanning 4 generations. Marked hypertension (diastolic pressure of 105 mm/Hg) was the presenting symptom in all patients. Eleven patients developed end-stage renal disease between ages 19 and 50 years. Seven underwent renal transplantation and 3 were on hemodialysis. Laboratory studies showed increased serum creatinine, but urine analysis was normal, with no evidence of proteinuria. None of the patients had any extrarenal manifestations. Renal biopsy reports were available from 2 patients. One had some sclerotic glomeruli with interstitial fibrosis and mild tubular atrophy. The other showed mild thinning of the membranes without other significant findings. No abnormalities were seen after immunofluorescent staining for IgG, IgA, IgM, C3 (120700), C4 (see 120810), C1q (see 120550), properdin (300383), fibrinogen (see 134820), and albumin (103600). Whether the hypertension was the primary cause of the renal failure or secondary to an underlying renal defect was unclear.
The transmission pattern of adult-onset nephropathy and hypertension in the family reported by Cohn et al. (2000) was consistent with autosomal dominant inheritance.
By genomewide linkage analysis of a large Israeli family with nephropathy and hypertension, Cohn et al. (2000) identified a candidate disease locus on chromosome 1q21; maximum lod score = 4.71 at a recombination fraction of zero with D1S305. Recombination mapping defined an interval of approximately 11.6 cM between the markers at D1S2696 and D1S2635. Cohn et al. (2000) concluded that the disorder in the family they studied was distinct from the form of autosomal dominant medullary cystic kidney disease (MCKD1; 174000) that maps to 1q21. They noted that the gene encoding atrial natriuretic peptide receptor-1 (NPR1; 108960) had been mapped to this region. They suggested that although mice homozygous for a knockout mutation in the mouse Npr1 gene did not have nephritis or other obvious abnormalities of the kidney accompanying their hypertension, there may not have been time for this to develop. A polymorphic allele of NPR1 is associated with essential hypertension (Nakayama et al., 2000). Thus, NPR1 remained a candidate disease gene for the nephropathy/hypertension phenotype present in the family they described.
There are several early reports of hereditary nephropathy and/or nephritis in the literature. Affected kindreds were reported by Goldman and Haberfelde (1959), Ben-Ishay et al. (1967), Albert et al. (1969), and Pashayan et al. (1971).
Teisberg et al. (1973) presented evidence suggesting an inherited defect in immune function; serum from their patients was unable to lyse the third component of complement in vitro. This may have been a form of atypical autoimmune hemolytic anemia (see AHUS1; 235400).
Albert, M. S., Leeming, J. M., Wigger, H. J. Familial nephritis associated with the nephrotic syndrome. Am. J. Dis. Child. 117: 153-155, 1969. [PubMed: 5763827] [Full Text: https://doi.org/10.1001/archpedi.1969.02100030155006]
Ben-Ishay, D., Biran, S., Ullmann, T. D. Familial nephritis. Israel J. Med. Sci. 3: 106-112, 1967. [PubMed: 6030413]
Cohn, D. H., Shohat, T., Yahav, M., Ilan, T., Rechavi, G., King, L., Shohat, M. A locus for an autosomal dominant form of progressive renal failure and hypertension at chromosome 1q21. Am. J. Hum. Genet. 67: 647-651, 2000. [PubMed: 10930359] [Full Text: https://doi.org/10.1086/303051]
Dockhorn, R. J. Hereditary nephropathy without deafness. Am. J. Dis. Child. 114: 135-138, 1967. [PubMed: 4951535] [Full Text: https://doi.org/10.1001/archpedi.1967.02090230065004]
Goldman, R., Haberfelde, G. C. Hereditary nephritis: report of a kindred. New Eng. J. Med. 261: 734-738, 1959.
Nakayama, T., Soma, M., Takahashi, Y., Rehemudula, D., Kanmatsuse, K., Furuya, K. Functional deletion mutation of the 5-prime-flanking region of type A human natriuretic peptide receptor gene and its association with essential hypertension and left ventricular hypertrophy in the Japanese. Circ. Res. 86: 841-845, 2000. [PubMed: 10785505] [Full Text: https://doi.org/10.1161/01.res.86.8.841]
Pashayan, H., Fraser, F. C., Goldbloom, R. B. A family showing hereditary nephropathy. Am. J. Hum. Genet. 23: 555-567, 1971. [PubMed: 5132064]
Perkoff, G. T. The hereditary renal diseases. New Eng. J. Med. 277: 79-85 and 129-138, 1967. [PubMed: 5338472] [Full Text: https://doi.org/10.1056/NEJM196707132770206]
Reyersbach, G. C., Butler, A. M. Congenital hereditary hematuria. New Eng. J. Med. 251: 377-380, 1954. [PubMed: 13194078] [Full Text: https://doi.org/10.1056/NEJM195409022511003]
Richmond, J. M., Whitworth, J. A., Kincaid-Smith, P. S. Familial interstitial nephritis. Clin. Nephrol. 16: 109-113, 1981. [PubMed: 7296967]
Teisberg, P., Grottum, K. A., Myhre, E., Flatmark, A. L. In-vivo activation of complement in hereditary nephropathy. Lancet 324: 356-358, 1973. Note: Originally Volume II. [PubMed: 4124530] [Full Text: https://doi.org/10.1016/s0140-6736(73)93194-2]