ORPHA: 33364; DO: 0111869;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q14.3 | Trichothiodystrophy 2, photosensitive | 616390 | Autosomal recessive | 3 | ERCC3 | 133510 |
A number sign (#) is used with this entry because of evidence that photosensitive trichothiodystrophy-2 (TTD2) is caused by homozygous mutation in the ERCC3/XPB gene (133510), which encodes a helicase subunit of transcription/repair factor TFIIH, on chromosome 2q14.
Trichothiodystrophy is a rare autosomal recessive disorder in which patients have brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern, called 'tiger tail banding,' under polarizing microscopy. TTD patients display a wide variety of clinical features, including cutaneous, neurologic, and growth abnormalities. Common additional clinical features are ichthyosis, intellectual/developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections. There are both photosensitive and nonphotosensitive forms of the disorder. Patients with TTD have not been reported to have a predisposition to cancer (summary by Faghri et al., 2008).
For a discussion of genetic heterogeneity of TTD, see 601675.
Weeda et al. (1997) reported 2 sibs, born of consanguineous parents, with trichothiodystrophy. The proband, a male, had congenital ichthyosis (collodion baby). The skin condition improved within 3 weeks, leaving a mild ichthyosis of the trunk. TTD was suspected at 3 years of age, on the basis of mild ichthyosis of the trunk, with involvement of the scalp, palms, and soles; mild photosensitivity; lack of second upper incisor; and hair growing normally but coarse, with a tiger-tail pattern under polarized light. The diagnosis of TTD was confirmed by analysis of the amino acid content of hair, showing a decrease in cysteine residues. An older affected sister had a similar presentation as a collodion baby with favorable outcome. A diagnosis of TTD was confirmed by hair microscopy and biochemical analysis showing low cysteine content. Both the proband and his sister were in good general health, without physical and mental impairment, at the ages of 10 and 16 years, respectively. The description of these cases resembles that of the disorder referred to as Tay syndrome, or trichothiodystrophy with congenital ichthyosis.
In 2 sibs, born of consanguineous parents, with trichothiodystrophy Weeda et al. (1997) identified a homozygous thr119-to-pro (T119P; 133510.0003) substitution in the ERCC3 gene. The mutation occurred in a region of the XPB protein completely conserved in yeast, Drosophila, and human.
Faghri, S., Tamura, D., Kraemer, K. H., DiGiovanna, J. J. Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations. J. Med. Genet. 45: 609-621, 2008. [PubMed: 18603627] [Full Text: https://doi.org/10.1136/jmg.2008.058743]
Weeda, G., Eveno, E., Donker, I., Vermeulen, W., Chevallier-Lagente, O., Taieb, A., Stary, A., Hoeijmakers, J. H. J., Mezzina, M., Sarasin, A. A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy. Am. J. Hum. Genet. 60: 320-329, 1997. [PubMed: 9012405]