Juvenile cataract in Hutterites

Shokeir, M. H. K.; Lowry, R. Brian

doi:10.1002/ajmg.1320220307

Cited by 10 publications

(11 citation statements)

References 12 publications

(1 reference statement)

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“…Juvenile autosomal recessive cataracts have been reported in humans [12,13], and these recessive mutations, like the one described in this work, have not had measurable effects on growth or other aspects of development.…”

Section: Discussionmentioning

confidence: 80%

Localization of a Recessive Juvenile Cataract Mutation to Proximal Chromosome 7 in Mice

Cargill¹,

Happold²,

Bertani³

et al. 2001

Hum Hered

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Objective: To localize the chromosomal position of a novel cataract mutation (juvenile recessive cataract; jrc) in mice. Methods: A mapping population was developed by crossing cataract males (albino MH) to wild-type females (black C57BL/6J). F₁ females were backcrossed to albino MH males with cataracts. Results: The results were consistent with a model of a single autosomal recessive gene [153 cataract, 169 wild-type; χ² = 0.8, 1 degree of freedom (d.f.), p > 0.35]. Linkage with the albino (tyrosinase; Tyr) locus was evident (χ² = 61.5, 1 d.f., p < 0.0001), implicating chromosome 7 as the location of jrc. Recombination percentages (± SE) between jrc and D7Mit340 (1.2 cM location), D7Mit227 (16.0 cM) and D7Mit270 (18.0 cM) were 17.1 ± 2.1, 3.7 ± 1.1 and 6.2 ± 1.3%, respectively. Multi-point mapping determined that the most likely order of these loci is D7Mit340 – jrc – D7Mit227 – D7Mit270 – Tyr. Although animals with the mutant phenotype appeared to have little or no sense of sight, their growth was not different (p >0.20) from that of normal mice. Conclusion: The jrc mutation model may be useful in the study of the genetics of cataracts in other animal species, including humans.

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Section: Discussionmentioning

confidence: 80%

Localization of a Recessive Juvenile Cataract Mutation to Proximal Chromosome 7 in Mice

Cargill¹,

Happold²,

Bertani³

et al. 2001

Hum Hered

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“…Autosomal recessive inheritance of congenital cataracts is rare, although there have been some cases reported (Francois et al 1982;Macdonald et al 1983;Shokeir and Lowry 1985;Forsius et al 1992;Ippel et al 1994). Yamagucho presented evidence suggesting the linkage of Iiblood group located at 9q21 (Bierhuizen et al 1993) with a recessive form of congenital cataracts, and this linkage was confirmed later by Ogata et al (1979).…”

Section: Genetic Linkage Of Congenital Cataractsmentioning

confidence: 92%

Congenital cataracts: gene mapping

2000

Human Genetics

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“…Lowry and colleagues (Shokeir and Lowry ; Pearce et al. ) described nonsyndromic juvenile cataracts in a single large Hutterite family.…”

Section: Introductionmentioning

confidence: 99%

“…). The high coefficient of inbreeding and the pattern of trait segregation led Shokeir and Lowry () to hypothesize autosomal recessive inheritance for the cataract phenotype. In those several reports, age of onset ranged from infancy through school age, mostly between 3 and 7 years.…”

Section: Introductionmentioning

confidence: 99%

Hutterite‐type cataract maps to chromosome 6p21.32‐p21.31, cosegregates with a homozygous mutation in LEMD2, and is associated with sudden cardiac death

Boone

Yuan

et al. 2015

Molec Gen & Gen Med

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BackgroundJuvenile‐onset cataracts are known among the Hutterites of North America. Despite being identified over 30 years ago, this autosomal recessive condition has not been mapped, and the disease gene is unknown.MethodsWe performed whole exome sequencing of three Hutterite‐type cataract trios and follow‐up genotyping and mapping in four extended kindreds.ResultsTrio exomes enabled genome‐wide autozygosity mapping, which localized the disease gene to a 9.5‐Mb region on chromosome 6p. This region contained two candidate variants, LEMD2 c.T38G and MUC21 c.665delC. Extended pedigrees recruited for variant genotyping revealed multiple additional relatives with juvenile‐onset cataract, as well as six deceased relatives with both cataracts and sudden cardiac death. The candidate variants were genotyped in 84 family members, including 17 with cataracts; only the variant in LEMD2 cosegregated with cataracts (LOD = 9.62). SNP‐based fine mapping within the 9.5 Mb linked region supported this finding by refining the cataract locus to a 0.5‐ to 2.9‐Mb subregion (6p21.32‐p21.31) containing LEMD2 but not MUC21. LEMD2 is expressed in mouse and human lenses and encodes a LEM domain‐containing protein; the c.T38G missense mutation is predicted to mutate a highly conserved residue within this domain (p.Leu13Arg).ConclusionWe performed a genetic and genomic study of Hutterite‐type cataract and found evidence for an association of this phenotype with sudden cardiac death. Using combined genetic and genomic approaches, we mapped cataracts to a small portion of chromosome 6 and propose that they result from a homozygous missense mutation in LEMD2.

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Juvenile cataract in Hutterites

Cited by 10 publications

References 12 publications

Localization of a Recessive Juvenile Cataract Mutation to Proximal Chromosome 7 in Mice

Localization of a Recessive Juvenile Cataract Mutation to Proximal Chromosome 7 in Mice

Congenital cataracts: gene mapping

Hutterite‐type cataract maps to chromosome 6p21.32‐p21.31, cosegregates with a homozygous mutation in LEMD2, and is associated with sudden cardiac death

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