Rare etiology of autosomal recessive disease in a child with noncarrier parents.
A child with maple syrup urine disease type 2 (MSUD2) was found to be homozygous for a 10-bp MSUD2-gene deletion on chromosome 1. Both purported parents were tested, and neither carries the gene deletion. Polymorphic simple-sequence repeat analyses at 15 loci on chromosome 1 and at 16 loci on other chromosomes confirmed parentage and revealed that a de novo mutation prior to maternal meiosis I, followed by nondisjunction in maternal meiosis II, resulted in an oocyte with two copies of the de novo mutant allele. Fertilization by a sperm that did not carry a paternal chromosome 1 or subsequent mitotic loss of the paternal chromosome 1 resulted in the propositus inheriting two mutant MSUD2 alleles on two maternal number 1 chromosomes.
Center for Human Genetics, Department of Pediatrics, Boston University School of Medicine, Boston, MA, 02118, USA. rlebo@bu.edu
R V
RV
Lebo
L R
LR
Shapiro
E Y
EY
Fenerci
J M
JM
Hoover
J L
JL
Chuang
D T
DT
Chuang
D F
DF
Kronn
D000483:Alleles; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003434:Crossing Over, Genetic / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005808:Genes, Recessive / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008375:Maple Syrup Urine Disease / Q000235:genetics*; D008540:Meiosis / Q000235:genetics*; D008938:Mitosis / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D009630:Nondisjunction, Genetic; D009679:Nuclear Family; D009865:Oocytes / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism