Amish, Mennonite, and Hutterite
Genetic Disorder Database

Hypophosphatasia

Disorder
OMIM #: #241500  (Click to access OMIM database)
Disorder: Hypophosphatasia 
Also known as: HOPS 
Clinical
Phenotype: severe rachitic-like illness, bony ossification abnormalities, hypercalcemia, failure to thrive 
Seen In: Amish
Old Order Mennonite
Old Colony Mennonite
Unknown/Other Mennonite
Hutterite
Remarks:

Testing is available at LHSC.

Infantile forms are homozygous for the Gly334Asp (legacy Gly317Asp) mutation. Juvenile forms are heterozygous for Gly334Asp (legacy Gly317Asp) and Glu191Lys (legacy Glu174Lys). 

Mutations
1   Old Colony Mennonite, Hutterite  
Gene: ALPL
Base Change: G>A, at nucleotide 1001
Amino Acid Change: gly 334 --> asp
2   Old Colony Mennonite  
Gene: ALPL
Base Change: G>A, at nucleotide 571
Amino Acid Change: glu 191 --> lys
Last updated: 2020-02-03 

References
Boycott KM, Parboosingh JS, Chodirker BN, Lowry RB, McLeod DR, Morris J, Greenberg CR, Chudley AE, Bernier FP, Midgley J, Møller LB, Innes AM. (2008) Clinical genetics and the Hutterite population: a review of Mendelian disorders. Am J Med Genet A 146A(8):1088-98.
PubMed ID: 18348266 
Greenberg C, Evans J, McKendry-Smith S, Redekopp S, Haworth J, Mulivor R, Chodirker B. (1990) Infantile Hypophosphatasia: Localization within Chromosome Region 1p36.1-34 and Prenatal Diagnosis Using Linked DNA Markers. Am J Hum Genet 46: 286-292.
PubMed ID: 1689104 
Greenberg CR, Taylor C, Haworth J, Seargeant L, Philipps S, Triggs-Raine B, Chodirker BN. (1993) A Homoallelic Gly317>Asp Mutation in ALPL Causes the Perinatal (Lethal) Form of Hypophosphatasia in Canadian Mennonites. Genomics 17: 215-217.
PubMed ID: 8406453 
Hofmann C, Girschick H, Mornet E, Schneider D, Jakob F, Mentrup B. (2014) Unexpected high intrafamilial phenotypic variability observed in hypophosphatasia. Eur J Hum Genet Oct;22(10):1160-4.
PubMed ID: 24569605 
Leung EC, Mhanni AA, Reed M, Whyte MP, Landy H, Greenberg CR. (2013) Outcome of perinatal hypophosphatasia in manitoba mennonites: a retrospective cohort analysis. JIMD Rep 11:73-8.
PubMed ID: 23580367 
Lowry RB, Snyder FF, Wesenberg RL, Machin GA, Applegarth DA, Morgan K, Carter RJ, Toone JR, Holmes TM, Dewar RD. (1985) Morquio syndrome (MPS IVA) and hypophosphatasia in a Hutterite kindred. Am J Med Genet 22(3):463-75.
PubMed ID: 3933344 
Orton NC, Innes AM, Chudley AE, Bech-Hansen NT. (2008) Unique disease heritage of the Dutch-German Mennonite population. Am J Med Genet A 146A(8):1072-87.
PubMed ID: 18348259 

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