Abstract for presentation at 11th International Congress of Human Genetics

Cryptic Duplications: Detected by MLPA, not Detectable by FISH

  • Dr Sui Yu, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Dr Hong Pan, Department of Paediatrics, Peking University First Hospital, Beijing, China
  • Ms Kathy Cox, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Dr Drago Bratkovic, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Sharon Bain, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Sarah Smith, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Dr Elizabeth Thompson, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia
  • Prof Eric Haan, Department of Genetic Medicine, Women's and Children's Hospital, Adelaide, Australia

    • Fluorescence in situ hybridisation (FISH) has been the technology of choice in detecting subtelomere rearrangements and microdeletion syndromes for many years. However, tandem duplications are likely to be missed by FISH. Using multiplex ligation-dependent probe amplification (MLPA), we have re-analysed patients, who previously had normal FISH results, to look for tandem duplications in two groups of patients.
    The first group consisted of 140 patients with mental retardation, who had a normal subtelomere FISH result. We tested these patients using subtelomere MLPA kit P069 and identified one case of 9p duplication (1/140). The patient is a 3 year old male with macrocephaly, severe developmental delay, ASD, butterfly vertebrae (T10), vesicoureteric reflux and dysmorphism with hypertelorism, telecanthus, broad nasal bridge and tip, reduced frontonasal angle and a short philtrum. He shares some dysmorphisms with his mother who has a broad nasal bridge, short philtrum and hypertelorism. Parental testing has been arranged in order to distinguish between a normal variant and a pathological mutation.
    The second group consisted of 13 patients with congenital cardiac anomalies, who had a normal result for 22q deletion by FISH. We tested these patients using MLPA kit P023-Digeorge and identified a familial duplication in two siblings involving the region deleted in 22q11.2 deletion syndrome. The proband (female, 15-years) and her brother (13-years) are the children of non-consanguineous Caucasian parents; who could not be tested. Both patients had preauricular pits, heterochromic irides, intellectual disability (moderate), congenital heart disease (proband –VSD; brother -PDA and pulmonary stenosis) and dysmorphic features with prominent cheeks, deep set eyes and a thin upper lip. The proband also had brachydactyly, while her brother had macrocephaly with plagiocephaly, a submucous cleft and behavioural problems.
    Our experience demonstrates that MLPA has the advantage over FISH in detecting both deletions and duplications.

    Conference Organiser - ICMS Pty Ltd