title: Cockayne Syndrome due to a maternally-inherited whole gene deletion of ERCC8 and a paternally-inherited ERCC8 exon 4 deletion.
abstract: Cockayne Syndrome (CS) is an autosomal recessive disorder that causes neurological regression, growth failure and dysmorphic features. We describe a Chinese female child with CS caused by deletions of exon 4 of ERCC8 on one chromosome and exons 1-12 on the other chromosome. By using chromosomal microarray, multiplex ligation-dependant probe analysis and long range PCR, we showed that she inherited a 277 kb deletion affecting the whole ERCC8 gene from the mother and a complex rearrangement resulting in deletion of exon 4 together with a 1,656 bp inversion of intron 4 from the father. A similar complex rearrangement has been reported in four unrelated Japanese CS patients. Analysis of the deletion involving exon 4 identified LINE and other repeat elements that may predispose the region to deletions, insertions and inversions. The patient also had insulin-dependent diabetes mellitus, a rare co-existing feature in patients with CS. More research will be needed to further understand the endocrine manifestations in CS patients.
authors.affiliation: Genetics Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore. Electronic address: ting.teck.wah@kkh.com.sg.
authors.forename: T W
authors.initials: TW
authors.lastname: Ting
authors.affiliation: KK Research Centre, KK Women's and Children's Hospital, Singapore.
authors.forename: M S
authors.initials: MS
authors.lastname: Brett
authors.affiliation: Genetics Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore.
authors.forename: E S
authors.initials: ES
authors.lastname: Tan
authors.affiliation: Genetic Diagnostic Laboratory, Department of Laboratory Medicine, Children's Hospital, Boston, United States.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.affiliation: KK Research Centre, KK Women's and Children's Hospital, Singapore.
authors.forename: S P
authors.initials: SP
authors.lastname: Lee
authors.affiliation: KK Research Centre, KK Women's and Children's Hospital, Singapore.
authors.forename: E C
authors.initials: EC
authors.lastname: Lim
authors.affiliation: Endocrinology Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore.
authors.forename: R F
authors.initials: RF
authors.lastname: Vasanwala
authors.affiliation: Endocrinology Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore.
authors.forename: N
authors.initials: N
authors.lastname: Lek
authors.affiliation: Neurology Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore.
authors.forename: T
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Neurology Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore.
authors.forename: K W
authors.initials: KW
authors.lastname: Lim
authors.affiliation: KK Research Centre, KK Women's and Children's Hospital, Singapore.
authors.forename: E C
authors.initials: EC
authors.lastname: Tan
mesh_terms: D002675:Child, Preschool; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D003057:Cockayne Syndrome / Q000235:genetics*; D015897:Comorbidity; D045643:DNA Repair Enzymes / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D017384:Sequence Deletion; D057345:Sequence Inversion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C095472:ERCC8 protein, human; D014157:Transcription Factors; D045643:DNA Repair Enzymes
keywords: Cockayne syndrome; Growth failure; Neurological regression