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A ring chromosome X in a child with features of Kabuki Make-up syndrome

Journal Article · · American Journal of Human Genetics
OSTI ID:133719
; ;  [1]
  1. Children`s Hospital, San Diego, CA (United States); and others

The clinical features of this female patient (severe developmental delay, prominent finger pads, long palpebral fissures, short stature and history of hypotonia) suggested a diagnosis of Kabuki Make-up syndrome (KMS). Cytogenetic analyses showed this patient had a small ring X chromosome in 83% of cells and the parents were karyotypically normal. We hypothesized that deletion or rearrangement of X chromosome-derived sequences might be associated with the KMS-like phenotype observed in this patient. The breakpoints and parental origin of this small ring X were ascertained using a combination of genotyping with highly informative STRs and quantitative Southern blotting. PCR-based genotyping showed this female patient was heterozygous for X-linked loci SBMA (Xq11-q12) and DXS227 (Xq13.1). Hemizygosity was observed at several loci: DMD STR-49 (Xp21.2), DXS101 (Xq21.3), FMR-1 (Xq27.3) and DXYS64 (Xq28). Genotyping results at MIC2 (Xp22.3) and DXYS156 were not informative. These molecular genetic data indicate a large deletion of the distal long arm of the X chromosome and suggest a partial deletion of the distal short arm consistent with a small ring X chromosome with breakpoints near p21.2 and q13.1. This ring X chromosome is paternally-derived based on the observation that only the maternal alleles are inherited at three loci: (DMD STR-49, DXS101, and FMR-1). Studies to determine if the XIST gene at Xq13.3 is present and functioning on the ring chromosome are underway.

OSTI ID:
133719
Report Number(s):
CONF-941009--
Journal Information:
American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
Country of Publication:
United States
Language:
English

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