Sulfur-deficient Hair Research Articles

Novel contiguous gene deletion in peruvian girl with Trichothiodystrophy type 4 and glutaric aciduria type 3

Trichothiodystrophy type 4 is a rare autosomal recessive and ectodermal disorder, characterized by dry, brittle, sparse and sulfur-deficient hair and other features like intellectual disability, ichthyotic skin and short stature, caused by a homozygous mutation in MPLKIP gene. Glutaric aciduria type 3 is caused by a homozygous mutation in SUGCT gene with no distinctive phenotype. Both genes are localized on chromosome 7 (7p14).We report an 8-year-old female with short stature, microcephaly, development delay, intellectual disability and hair characterized for dark, short, coarse, sparse and brittle associated to classical trichorrhexis microscopy pattern. Chromosome microarray analysis showed a 125 kb homozygous pathogenic deletion, which includes genes MPLKIP and SUGCT, not described before. This is the first case described in Peru of a novel contiguous gene deletion of Trichothiodystrophy type 4 and Glutaric aciduria type 3 performed by chromosome microarray analysis, highlighting the contribution and importance of molecular technologies on diagnosis of rare genetic conditions.

Mutations in the TTDN1 Gene Are Associated with a Distinct Trichothiodystrophy Phenotype

Trichothiodystrophy (TTD) is a rare multisystem disorder, characterized by sulfur deficient hair with alternating dark and light “tiger tail” banding on polarized light microscopy. TTD is caused by mutations in DNA repair/transcription genes XPD, XPB or TTDA, and in TTDN1, a gene of unknown function. While most TTD patients are photosensitive, patients with TTDN1 mutations were reported to be non-photosensitive. We followed a cohort of 36 TTD patients from 2001 to 2013. We describe 5 patients from 4 families with defects in the TTDN1 gene: 4 had no photosensitivity while 1 patient exhibited cutaneous burning. Deep phenotyping of our cohort revealed differences between the patients with and without TTDN1 mutations. Delayed bone age and seizure disorders were overrepresented in the TTDN1 group (p=0.009 and p=0.024, respectively), while some characteristic TTD clinical, laboratory, and imaging findings were absent. The 3 oldest TTDN1 patients displayed autistic behaviors in contrast to the characteristic friendly, socially interactive personality in the other patients. DNA sequencing revealed deletion mutations in TTDN1 ranging in size from a single base pair to over 120kb. These data identify a distinct phenotype relationship in TTD caused by TTDN1 mutations and suggest a different mechanism of disease.

Trichothiodystrophy in a child with occult learning disorder

Trichothiodystrophy (TTD) is an autosomal recessive condition characterized by brittle and sparse sulfur deficient hair. The disorder is due to a known genetic mutation in DNA nucleotide excision repair (NER) in up to 83% of cases. We describe a 13-month-old girl presenting with hair fragility and hair loss since age 3 months, and discuss the overlap between TTD and other NER diseases. This case report highlights the importance of early diagnosis of occult learning disorder in young children with TTD and the need for early assessment and involvement of multidisciplinary team to target the child's educational needs.

Trichothiodystrophy and fragile hair: the distinction between diagnostic signs and diagnostic labels in childhood hair disease

Hair typically becomes fragile when there are structural abnormalities and/or a reduction in the sulphur-containing amino acids cystine or methionine. This finding in the setting of a neuroectodermal complaint is usually labelled trichothiodystrophy (TTD). The spectrum of features within this diagnostic grouping tests the validity of using sulphur-deficient hair as a central characteristic. To determine what diagnoses were found within a group of subjects with fragile hair and whether low cystine or methionine were relevant central characteristics. We examined cases referred to us from 12 U.K. centres for hair microscopy over 10 years where hair fragility or clinical characteristics raised the possibility of TTD. All samples underwent amino acid analysis. This was achieved through cation exchange chromatography coupled with spectrophotometric quantification. Twenty-five patients (11 male, 14 female) with a mean age of 11 years (0.3-37) were evaluated. Nineteen patients had features of hair damage. Of these, five patients had abnormalities on microscopy only and four patients had microscopic changes and tiger-tail pattern but normal amino acid content. The remaining 10 patients had reduced cystine content, two of whom also had low methionine. All but one had the tiger-tail pattern. Among the wide range of phenotypes there were only three cases matching a diagnosis of TTD. Our data suggest that clinically apparent fragile hair in childhood is only rarely associated with a diagnosis of TTD. The tiger-tail change is sensitive but not wholly specific to TTD. We propose that the term trichothiodystrophy be limited in its use to define sulphur-deficient hair rather than as a diagnostic term in a heterogeneous and incoherent multisystem disorder, where sulphur-deficient hair is one feature.

Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations

Trichothiodystrophy (TTD) is a rare, autosomal recessive disease, characterised by brittle, sulfur deficient hair and multisystem abnormalities. A systematic literature review identified 112 patients ranging from 12 weeks to 47...

Nucleotide excision repair and cancer

Nucleotide excision repair (NER) is the most versatile and best studied DNA repair system in humans. NER can repair a variety of bulky DNA damages including UV-light induced DNA photoproducts. NER consists of a multistep process in which the DNA lesion is recognized and demarcated by DNA unwinding. Then, an approximately 28 bp DNA damage containing oligonucleotide is excised followed by gap filling using the undamaged DNA strand as a template. The consequences of defective NER are demonstrated by three rare autosomal-recessive NER-defective syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). XP patients show severe sun sensitivity, freckling in sun exposed skin, and develop skin cancers already during childhood. CS patients exhibit sun sensitivity, severe neurologic abnormalities, and cachectic dwarfism. Clinical symptoms of TTD patients include sun sensitivity, freckling in sun exposed skin areas, and brittle sulfur-deficient hair. In contrast to XP patients, CS and TTD patients are not skin cancer prone. Studying these syndromes can increase the knowledge of skin cancer development including cutaneous melanoma as well as basal and squamous cell carcinoma in general that may lead to new preventional and therapeutic anticancer strategies in the normal population.

Behavioural aspects of Pollitt syndrome: a 32-year follow-up of a case described by R. J. Pollitt and colleagues in 1968.

In 1968, R. J. Pollitt and colleagues described a syndrome characterized by abnormally brittle, sulphur-deficient hair (trichothiodystrophy), intellectual disability (ID) and growth retardation. One of the two siblings originally described by the above authors has recently been re-assessed by the present authors following a referral for advice about ritualistic behaviours. Her current clinical features are described, and the literature concerning trichothiodystrophy and ID is summarized.

Central nervous system dysmyelination in PIBI(D)S syndrome: a further case

This is a report of new case of PIBI(D)S, a rare autosomal recessive syndrome characterized by photosensitivity, ichthyosis, brittle sulfur-deficient hair (trichothiodystrophy), impaired intelligence, decreased fertility, and short stature. Bilateral cataract and axial osteosclerosis were also detected. Magnetic resonance imaging (MRI) revealed diffuse central nervous system dysmyelination, a finding also described in the only three other reported cases in which MRI was performed. The paper also considers certain similarities in neurological signs and neuroradiological findings between PIBI(D)S, Cockayne syndrome, and xeroderma pigmentosum--all of which are inherited diseases characterized by photosensitivity and DNA repair defect.

Syndromes associate with trichotodystrophy

Sparse, brittle, sulphur-deficient hair is an excellent marker for several autosomal recessive neurocutaneous syndromes. The term 'trichothiodystrophy' is commonly used in publications on such syndromes and the best characterized trichothiodystrophy syndrome is associated with skin photosensitivity and intellectual impairment. Patients with these three cardinal signs usually have an underlying DNA repair defect. Here we describe clinical and laboratory findings in two patients with trichothiodystrophy and defective DNA repair alongside findings in three other cases who have different trichothiodystrophy syndromes without defective DNA repair. These patients' features are discussed in the light of a practical classification scheme which is based upon a check-list of clinical abnormalities associated with trichothiodystrophy syndromes (Van Neste, 1991).

Trichothiodystrophy associated with photosensitivity, gonadal failure, and striking osteosclerosis

Three new unrelated cases of PIBIDS (Photosensitivity, Ichthyosis, Brittle, sulfur-deficient hair [trichothiodystrophy], Impaired intelligence, Decreased fertility, and Short stature) are reported. Decreased survival of skin fibroblast lines after UVB exposure was found. All three male patients had hypogonadism and primary end-organ gonadal failure. Striking osteosclerosis was present in all three patients. To the best of our knowledge the third patient is the first reported case of a black man with PIBIDS.

Weathering of hair in trichothiodystrophy.

The structure of hairs from three patients with sulphur-deficient hair, trichothiodystrophy, has been studied by light, plane-polarizing and scanning electron microscopy. Severe cuticular and secondary cortical degeneration was evident along almost the entire length of the hair shaft, with cuticle loss, trichorrhexis nodosa formation and trichoschisis. The severity of these changes varied between patients. The role of the cuticle in protecting hair from environmental damage is discussed.