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Comprehensive Clinical and Molecular Analysis of Trichothiodystrophy Patients with Mutations in the TTDN1 Gene

Monday, September 22, 2014 — Poster Session II

4:00 p.m. – 6:00 p.m.

FAES Academic Center




  • S. G. Khan
  • E. R. Heller
  • D. Tamura
  • J. J. DiGiovanna
  • K. H. Kraemer


Trichothiodystrophy (TTD) is a rare, autosomal-recessive disorder with a wide-spectrum of clinical manifestations. We followed a cohort of 36 TTD-patients from 2001 to 2013. Most TTD patients with defects in NER genes: XPD, XPB or TTDA are photosensitive. However, patients with mutations in TTDN1 (C7ORF11), a gene of unknown function, have been reported to be non-photosensitive. We describe 5 TTD-patients (age 1 to 14 yrs) from 4 families with defects in TTDN1 gene: 1 was photosensitive (TTD343BE) and 4 were non-photosensitive (TTD402BE, TTD480BE, and siblings TTD487BE and TTD488BE). Post-UV cell-survival indicates that fibroblasts from non-photosensitive and photosensitive TTDN1 patients are not hypersensitive. DNA sequencing revealed 2 distinct initiation codon mutations in TTD402BE, and deletions ranging from single nucleotide to large size in others. Careful clinical-examination revealed phenotypic differences between patients with TTDN1 mutations and the 31 other TTD patients. Delayed bone age was overrepresented in the TTDN1-patients. TTDN1-patients did not have low MCV, elevated hemoglobin A2, osteosclerosis of the central skeleton, or dysmyelination on brain MRI, reduced height and weight, low birth-weight, collodian-membrane nor congenital cataracts frequently seen in the TTD-patients. These data identify a unique genotype-phenotype correlation in TTDN1 and suggest a different mechanism of disease in these patients.

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