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 homoz ygous for a 10-bp MSUD2-gene deletion on chromosome 1. Both purported paren ts were tested, and neither carries the gene deletion. Polymorphic simple-s equence 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, r esulted in an oocyte with two copies of the de novo mutant allele. Fertiliz ation by a sperm that did not carry a paternal chromosome 1 or subsequent m itotic loss of the paternal chromosome 1 resulted in the propositus inherit ing two mutant MSUD2 alleles on two maternal number 1 chromosomes.