title: Gonadal mosaicism as a rare cause of autosomal recessive inheritance.
abstract: Autosomal recessive diseases are typically caused by the biparental inheritance of familial mutant alleles. Unusual mechanisms by which the recessiveness of a mutant allele is unmasked include uniparental isodisomy and the occurrence of a de novo chromosomal rearrangement that disrupts the other allele. Gonadal mosaicism is a condition in which a postfertilization mutation is confined to the gamete precursors and is not detected in somatic tissues. Gonadal mosaicism is known to give the impression of autosomal recessive inheritance when recurrence of an autosomal-dominant condition among offspring of phenotypically normal parents is observed. Here, we report an extremely rare event in which maternal gonadal mosaicism for a recessive mutation in COL4A4 caused the recurrence of Alport syndrome within a consanguineous family. Such rare occurrence should be taken into account when analyzing pedigrees both for clinical and research purposes.
authors.affiliation: Department of Genetics.
authors.forename: S
authors.initials: S
authors.lastname: Anazi
authors.forename: E
authors.initials: E
authors.lastname: Al-Sabban
authors.forename: F S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000235:genetics; D003241:Consanguinity; D059472:Exome; D005260:Female; D005808:Genes, Recessive; D018095:Germ-Line Mutation; D006066:Gonads / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation; D009394:Nephritis, Hereditary / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree
chemical_list: C466620:COL4A4 protein, human; D024141:Collagen Type IV
keywords: Alport; COL4A4; autosomal recessive; consanguinity; gonadal mosaicism