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Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025.

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

, MD
Senior Editor, GeneReviews
Clinical Professor, Department of Pediatrics
University of Washington
Seattle, Washington

Initial Posting: .

Estimated reading time: 1 minute

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 Māori 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.

Table.

Genetic Disorders Associated with Founder Variants Common in the Māori Population

GeneDisorderMOIDNA Nucleotide ChangePredicted Protein Change% of Pathogenic Variants in Gene 1Carrier FrequencyEthnicityReference SequencesReferences
ADAMTSL4 Ectopia lentis (See ADAMTSL4-Related Eye Disorders.)ARc.2237G>Ap.Arg746His~100% 21/132Māori NM_019032​.6
NP_061905​.2
van Bysterveldt et al [2017]
CDH1 Hereditary diffuse gastric cancer ADc.190C>Tp.Gln64Ter24%NAMāori NM_004360​.5
NP_004351​.1
Hakkaart et al [2019]
c.1792C>Tp.Arg598Ter24%
c.2287G>Tp.Glu763Ter24%
c.2386dupCp.Arg796ProfsTer1124%
NPHS1 Congenital nephrotic syndrome (OMIM 256300)ARc.2131C>Ap.Arg711Ser82%UnknownMāori NM_004646​.4
NP_004637​.1
Wong et al [2013]
PDE6B Retinitis pigmentosa 40 (OMIM 613801)ARc.2197G>Cp.Ala733Pro~100% 21/124Māori NM_000283​.4
NP_000274​.3
Vincent et al [2017]

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

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; NA = not applicable

1.

This percentage does not account for the possibility of rare de novo pathogenic variants occurring in this population.

2.

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

References

  • Hakkaart C, Ellison-Loschmann L, Day R, Sporle A, Koea J, Harawira P, Cheng S, Gray M, Whaanga T, Pearce N, Guilford P. Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori. Fam Cancer. 2019;18:83–90. [PMC free article: PMC6323075] [PubMed: 29589180]
  • van Bysterveldt KA, Al Taie R, Ikink W, Oliver VF, Vincent AL. ADAMTSL4 assessment in ectopia lentis reveals a recurrent founder mutation in Polynesians. Ophthalmic Genet. 2017;38:537–43. [PubMed: 28394649]
  • Vincent AL, Abeysekera N, van Bysterveldt KA, Oliver VF, Ellingford JM, Barton S, Black GC. Next-generation sequencing targeted disease panel in rod-cone retinal dystrophies in Māori and Polynesian reveals novel changes and a common founder mutation. Clin Exp Ophthalmol. 2017;45:901–10. [PubMed: 28488341]
  • Wong W, Morris MC, Kara T. Congenital nephrotic syndrome with prolonged renal survival without renal replacement therapy. Pediatr Nephrol. 2013;28:2313–21. [PubMed: 23949594]

Revision History

  • 12 January 2023 (sw) Initial posting
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