March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Novel Stra6 Null Mutations In The Original Patient With Matthew-wood Syndrome
Author Affiliations & Notes
  • Francesca Pasutto
    Human Genetics, Erlangen-Nuremberg Univ Hosp, Erlangen, Germany
  • Frances Flinter
    Genetics Department, Guy's Hospital, London, United Kingdom
  • André Reis
    Human Genetics, Erlangen-Nuremberg Univ Hosp, Erlangen, Germany
  • Anita Rauch
    Human Genetics, University of Zurich, Zurich, Switzerland
  • Footnotes
    Commercial Relationships  Francesca Pasutto, None; Frances Flinter, None; André Reis, None; Anita Rauch, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 4929. doi:
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      Francesca Pasutto, Frances Flinter, André Reis, Anita Rauch; Novel Stra6 Null Mutations In The Original Patient With Matthew-wood Syndrome. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4929.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Microphthalmia/anophthalmia can be associated with craniofacial dysmorphic features, heart and vascular malformation, skeletal and limb anomalies, skin or gut defects, mental retardation and hydrocephalus, or combinations thereof.The combination of anophthalmia with pulmonary hyploplasia, diaphragmatic hernia and a cardiac malformation was originally referred as Matthew-Wood syndrome (MWS) by Seller in 1996, while in 2007 Chitayat devised the acronym of PDAC (Pulmonary hyploplasia,/agenesis, Diaphragmatic hernia/eventration, Anophthalmia/microphthalmia and Cardiac defect). Mutations in STRA6 have been reported in patients with an extremely variable clinical phenotype resembling MWS and PDAC syndrome thus considering them as different diseases. In fact, to date STRA6 mutations in the original patient with MWS (Seller 1996) had not been detected. Thus, our aim is to show that the original MWS phenotype is caused by mutations in STRA6.

Methods: : Fetal DNA was extracted from tissue using phenol/chloroform methodology and DNA from the parents was extracted from blood using the Chemagen System. The entire coding regions of STRA6, as well as the flanking intronic regions, were sequenced in both directions on an ABI 3730 machine. All sequences were analysed with the Sequencer software program v.4.9 (GeneCodes) and compared with database references (NM_022369, NT_010194).

Results: : We identified two novel sequence alterations in STRA6 in exons 6 and 15: a heterozygous deletion of two nucleotides, c.343-344delTG, predicting a frameshift with a premature stop codon at position 138 of the protein, p.Cys115PhefsX24; and a heterozygous transition, c.1177C>T, resulting in the generation of a stop codon at position 393 of the protein, Arg393X. The fetus's parents were also tested for both STRA6 mutations and we could confirm that the mutations were occurring in trans, consistent with autosomal recessive inheritance. We excluded the presence of both alleles in a further 190 healthy subjects by sequence analysis of exons 6 and 15.A meta-analysis of the phenotypes among all the patients with MWS and PDAC syndrome identified to date and carrying a truncating mutation in STRA6 shows no specific genotype/phenotype correlation and presents also an intra familial variation in disease severity.

Conclusions: : We conclude that mutations in STRA6 are indeed responsible for Matthew-Wood syndrome which share common clinical features both with PDAC syndrome and with the "syndromic microphthalmia 9" (MCOPS9, OMIM601186), a term later adopted by the Mendelian Inheritance in Man database. On the basis of their common clinical features we suggest a detailed reclassification of this phenotype under the original name of Matthew-Wood syndrome.

Keywords: candidate gene analysis • mutations • development 

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