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Resources for Genetics Professionals — Genetic Disorders Associated with Founder Variants Common in the Navajo Population

, MD and , PhD.

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A founder variant is a pathogenic variant observed at high frequency in a specific population due to the presence of the variant in a single ancestor or small number of ancestors. The presence of a founder variant can affect the approach to molecular genetic testing. When one or more founder variants account for a large percentage of all pathogenic variants found in a population, testing for the founder variant(s) may be performed first. The table below includes common founder variants — here defined as three or fewer variants that account for >50% of the pathogenic variants identified in a single gene in individuals of a specific ancestry — in individuals of Navajo ancestry. Note: Pathogenic variants that are common worldwide due to a DNA sequence hot spot are not considered founder variants and thus are not included.


Genetic Disorders Associated with Founder Variants Common in the Navajo Population

DisorderMOIGeneDNA Nucleotide ChangePredicted Protein ChangeProportion of Pathogenic Variants in This GeneCarrier FrequencyEthnicity (Specific Region)Reference SequencesReferences
Arylsulfatase A deficiencyARARSAc.854+1G>A--~100% 11/25 to 1/50Navajo
(Western Navajo Nation)
NM_000487​.5Pastor-Soler et al [1994], Holve et al [2001]
Microvillus inclusion disease
(OMIM 251850)
ARMYO5Bc.1979C>Tp.Pro660Leu~100% 1UnknownNavajoNM_001080467​.2
Erickson et al [2008]
Navajo brain stem syndrome
(OMIM 601536)
ARHOXA1c.76C>Tp.Arg26Ter~100% 1UnknownNavajoNM_005522​.4
Tischfield et al [2005]
Navajo neurohepatopathy
(MPV17-related mitochondrial DNA maintenance defect)
ARMPV17c.149G>Ap.Arg50Gln~100% 1~1/20NavajoNM_002437​.4
Karadimas et al [2006]
Oculocutaneous albinism type 2AROCA2g.103171_225796del
(122.5-kb del, incl exons 10-20) 2
--~100% 1~1/22NavajoNG_009846​.1Yi et al [2003]
Paget's disease
(OMIM 239000)
(~100 kb del, incl entire gene2
--~100% 1UnknownNavajoNC_000008​.10Whyte et al [2002]
Poikiloderma with neutropeniaARUSB1c.499delAp.(Thr160ProfsTer98)~100% 1UnknownNavajoNM_024598​.3
Clericuzio et al [2011]
Severe combined immunodeficiency (SCID-A)
(OMIM 602450)
ARDCLRE1Cc.597C>Ap.Tyr199Ter~100% 1~1/20 to 1/25NavajoNM_001033855​.2
Kwan et al [2015]

Included if ≤3 pathogenic variants account for ≥50% of variants identified in a specific ethnic group


To date, additional pathogenic variants in this gene have not been reported in individuals of Navajo descent.


Does not conform to standard HGVS nomenclature


  • Clericuzio C, Harutyunyan K, Jin W, Erickson RP, Irvine AD, McLean WH, Wen Y, Bagatell R, Griffin TA, Shwayder TA, Plon SE, Wang LL. Identification of a novel C16orf57 mutation in Athabaskan patients with poikiloderma with neutropenia. Am J Med Genet A. 2011;155A:337–42. [PMC free article: PMC3069503] [PubMed: 21271650]
  • Erickson RP, Larson-Thomé K, Valenzuela RK, Whitaker SE, Shub MD. Navajo microvillous inclusion disease is due to a mutation in MYO5B. Am J Med Genet A. 2008;146A:3117–9. [PubMed: 19006234]
  • Holve S, Hu D, McCandless SE. Metachromatic leukodystrophy in the Navajo: fallout of the American-Indian Wars of the nineteenth century. Am J Med Genet. 2001;101:203–8. [PubMed: 11424134]
  • Karadimas CL, Vu TH, Holve SA, Chronopoulou P, Quinzii C, Johnsen SD, Kurth J, Eggers E, Palenzuela L, Tanji K, Bonilla E, De Vivo DC, DiMauro S, Hirano M. Navajo neurohepatopathy is caused by a mutation in the MPV17 gene. Am J Hum Genet. 2006;79:544–8. [PMC free article: PMC1559552] [PubMed: 16909392]
  • Kwan A, Hu D, Song M, Gomes H, Brown DR, Bourque T, Gonzalez-Espinosa D, Lin Z, Cowan MJ, Puck JM. Successful newborn screening for SCID in the Navajo Nation. Clin Immunol. 2015;158:29–34. [PMC free article: PMC4420660] [PubMed: 25762520]
  • Pastor-Soler NM, Rafi MA, Hoffman JD, Hu D, Wenger DA. Metachromatic leukodystrophy in the Navajo Indian population: a splice site mutation in intron 4 of the arylsulfatase A gene. Hum Mutat. 1994;4:199–207. [PubMed: 7833949]
  • Tischfield MA, Bosley TM, Salih MA, Alorainy IA, Sener EC, Nester MJ, Oystreck DT, Chan WM, Andrews C, Erickson RP, Engle EC. Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development. Nat Genet. 2005;37:1035–7. [PubMed: 16155570]
  • Whyte MP, Obrecht SE, Finnegan PM, Jones JL, Podgornik MN, McAlister WH, Mumm S. Osteoprotegerin deficiency and juvenile Paget's disease. N Engl J Med. 2002;347:175–84. [PubMed: 12124406]
  • Yi Z, Garrison N, Cohen-Barak O, Karafet TM, King RA, Erickson RP, Hammer MF, Brilliant MH. A. 122.5-kilobase deletion of the P gene underlies the high prevalence of oculocutaneous albinism type 2 in the Navajo population. Am J Hum Genet. 2003;72:62–72. [PMC free article: PMC420013] [PubMed: 12469324]
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