title: Massive CAG repeat expansion and somatic instability in maternally transmitted infantile spinocerebellar ataxia type 7.
abstract: OBJECTIVE
  We report the first case to date of maternally transmitted infantile spinocerebellar ataxia type 7 (SCA7), in which a tract of (CAG)45 expands to lengths as large as (CAG)92-250.
  
  
  METHODS
  A 38-year-old woman with classic SCA7 (and a son, who died at age 3 years) had pronounced cerebellar atrophy and a renal biopsy specimen that showed focal segmental glomerulosclerosis with abnormal podocytes containing cytoplasmic inclusions. Polymerase chain reaction amplification across the SCA7 repeat tract assessed expansion levels in tissues of the affected son. High levels of somatic CAG instability were observed in blood, kidney, and skeletal muscle. This transmitted expansion is considerably larger than previously reported maternal transmission expansions of 5 to 10 gained repeats.
  
  
  CONCLUSIONS
  We document the first intertissue CAG instability reported to date in patients with SCA7, similar to SCA7 mouse models. Infantile SCA7, which is often paternally transmitted, can rarely arise by maternal transmission, which has implications for diagnosis and counseling among families of patients with SCA7.
authors.affiliation: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Trang
authors.affiliation: Program of Genetics and Genome Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sabrina Y
authors.initials: SY
authors.lastname: Stanley
authors.affiliation: Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Thorner
authors.affiliation: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hannaneh
authors.initials: H
authors.lastname: Faghfoury
authors.affiliation: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada2Program of Genetics and Genome Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze
authors.affiliation: Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.affiliation: Program of Genetics and Genome Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada4Program of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Pearson
authors.affiliation: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada5Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Grace
authors.initials: G
authors.lastname: Yoon
mesh_terms: D000328:Adult; D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*