Trichothiodystrophy Research Articles

Application Of Neuro-Fuzzy Expert System For The Probe And Prognosis Of Thyroid Disorder

Thyroid disorders are common disorders of the thyroid gland. Thyroid disorders include such diseases and conditions as graves disease, thyroid nodules, Hashimoto's thyroiditis, trauma to the thyroid, thyroid cancer and birth defects. These include being born with a defective thyroid gland or without a thyroid gland. Thyroid disorder can be caused by hyperthyroidism, thyroid cancer, goiter, hyperparathyroidism and postpartum thyroiditis. Thyroid disorder are usually characterized by life threatening symptoms such as insomnia, irritability, nervousness, unexplained weight loss, heat sensitivity, increased perspiration, thinning of skin, warm skin, fine hair, brittle hair and thinning hair. Neuro-Fuzzy Logic explores approximation techniques from neural networks to finds the parameter of a fuzzy system. This paper which demonstrates the practical application of Information Technology (IT) in the health sector, has presented a hybrid neuro-fuzzy Expert System to help in diagnosis of thyroid disorder using a set of symptoms. The system designed is an interactive system that tells the patient his current condition as regards thyroid disorder.

An usual cause of progressive hair loss

A 42-year-old man presented to the emergency department(ED) with progressive hair loss. He had no medical prob-lems, and did not take any medications. He was homo-sexual with multiple partners, and he denied alcohol orillicit drug use. He reported having had a penile lesion4 months prior, which was painless and resolved on itsown. The vital signs were normal. The physical examina-tion revealed a patchy distribution of hair loss over hisentire scalp (Fig. 1), without broken hairs or signs ofexcoriation or irritation.DiscussionAcute onset hair loss is a relatively uncommon presentationin the ED. It is a phenomenon with a multitude of potentialetiologies that range in severity from the innocuous to lifethreatening. These include several endocrine disorders,autoimmune disease, fungal and bacterial infections, self-induced trichotillomania, chemical mistreatment of hair, amedication related side effect, and far more, rare anddangerous poisoning and radiation exposure.Though the differential diagnosis is broad, an assess-ment of patients’ medical history, along with their symp-toms and signs, may help clinicians narrow the list ofpossible etiologies. Alopecia associated with radiationexposure or poisoning with a compound like thallium, forexample, will also be associated with acute gastrointestinaltoxicity, muscle weakness, and altered mental status.Chemotherapy related hair loss has an estimated incidenceof 65%, and is associated with particular cytotoxic agentsincluding paclitaxel, doxorubicin, and cyclophosphamide,to name just a few [1]. Tineacapitus, a fungal infection ofthe hair shafts or cuticles, will lead to brittle hair prone tobreakage. Similarly, tricotillomania may be identified by anexamination of the hair and scalp that may demonstratebroken hairs of various lengths or torn away follicles withexudates or hemorrhage. Alopecia areata is defined assudden onset, well demarcated, localized hair loss, usuallyon the scalp. If this pattern of hair loss is observed, labo-ratory evaluation is warranted as this entity is associatedwith several thyroid and autoimmune disorders [2].The patient illustrated in the photograph, however, had apeculiar moth-eaten pattern of hair loss that did not fall intoone of the categories of disorders already discussed. Uponlearning of the patient’s sexual history, however, a rapidplasma regain (RPR) was ordered with confirmatory trep-onemal antibody testing—both of which proved reactive.The patient was called back to the ED for treatment, oncethe results became available.DiagnosisAlopecia syphilitica. The first reported case of syphilisoccurred in the year 1494 in Naples, Italy, and was sub-sequently called the Great Pox as the infection spreadthroughout Europe over the following decades [3]. After aprecipitous decline in incidence with the discovery ofpenicillin, there has been a re-emergence of syphilis amongindividuals of all sexual orientations [4].The spiral-shaped bacteria Treponemapallidum inocu-lates an individual through mucosal surfaces or abradedskin. Primary syphilis represents localized replication, andmanifests itself as a painless, ulcerated lesion, 9–90 days

Ocular Manifestations of Trichothiodystrophy

Trichothiodystrophy (TTD) is a rare, autosomal recessive disorder characterized by sulfur-deficient brittle hair and multisystem abnormalities. Many TTD patients have a defect in known DNA repair genes. This report systematically evaluates the ocular manifestations of the largest-to-date cohort of TTD patients and xeroderma pigmentosum (XP)/TTD patients. Case series. Thirty-two participants, ages 1 to 30 years, referred to the National Eye Institute for examination from 2001 to 2010; 25 had TTD and 7 had XP/TTD. Complete, age- and developmental stage-appropriate ophthalmic examination. Visual acuity (VA), best-corrected VA, ocular motility, state of the ocular surface and corneal endothelial cell density, corneal diameter, and lens assessment. Developmental abnormalities included microcornea (44% TTD), microphthalmia (8% TTD, 14% XP/TTD), nystagmus (40% TTD), and infantile cataracts (56% TTD, 86% XP/TTD). Corrective lenses were required by 65% of the participants, and decreased best-corrected VA was present in 28% of TTD patients and 71% of XP/TTD patients. Degenerative changes included dry eye (32% TTD, 57% XP/TTD) and ocular surface disease identified by ocular surface staining with fluorescein (32% TTD) that usually are exhibited by much older patients in the general population. The 2 oldest TTD patients exhibited clinical signs of retinal/macular degeneration. Four XP/TTD patients presented with corneal neovascularization. These TTD and XP/TTD study participants had a wide variety of ocular findings including refractive error, infantile cataracts, microcornea, nystagmus, and dry eye/ocular surface disease. Although many of these can be ascribed to abnormal development--likely owing to abnormalities in basal transcription of critical genes--patients may also have a degenerative course. Proprietary or commercial disclosures may be found after the references.

Bubble hair and other acquired hair shaft anomalies due to hot ironing on wet hair

Bubble hair is an acquired hair shaft abnormality characterized by multiple airfilled spaces within the hair shaft. It is a result of thermal injury. We report a classic case of 22-year-old female who complained of dry brittle hair of two-week duration. Patient had used hot iron on wet hair twice to straighten hair. Hair microscopy was diagnostic and showed multiple air-filled spaces within the hair shaft.

Novel Mutation in Boy With Cartilage-hair Hypoplasia

Cartilage-hair hypoplasia (MIM 250250) is an autosomal recessive disease with diverse clinical manifestations. The clinical phenotypes include variable degrees of bone and hair dysplasia, deficient cellular and/or humoral immunity, and a predisposition to malignancy. We performed genetic studies of a patient with disproportionate short stature and brittle scalp hair. Genetic studies were also carried out in the patient's parents. A novel maternal mutation that consisted of a duplication of 14 nucleotides at position -13 of the RNA component of the RNA component of mitochondrial RNA processing endoribonuclease gene (RMRP; g. -26 to -13 dupTACTACTCTGTGAA, promoter region) and a paternal mutation base substitution of C to T at nucleotide + 230 (designated as + 1 in the transcription initiation site) in the coding sequence of RMRP were detected in this patient. A novel maternal RMRP mutation was found in a Chinese boy with typical cartilage-hair hypoplasia.

1110 Ectopic Neurohypophysis - Case Report

Background: Ectopic Neurohypophysis is a rare congenital anomaly of the pituitary gland associated with growth hormone and other anterior pituitary hormone deficiencies.Aims: To report a case of hypopituitarism due to ectopic neurohypophysis presenting with hypoglycemic seizures.Case report: A 7-year-old Romanian boy was admitted to our hospital with a generalized tonicclonic seizure associated with severe hypoglycemia (25mg/dL). His past medical history was remarkable for a perinatal history of asphyxia; congenital left eye strabismus; and three previous episods of hypoglicemic seizures with inconclusive metabolic and neurologic investigations. He was under treatment with carbamazepine for 3 months.According to his mother he had also language delay and growth retardation.The physical examination revealed a boy with a hoarse tone voice, dry skin, brittle hair, cold extremities and left eye convergent strabismus. His height was in the 3rd percentile (target height between 75th- 85th percentile).Laboratory studies showed hypercholesterolemia, normal values of ACTH, cortisol and TSH but abnormal low values of free T4 and IGF-1. Antithyroglobulin and antiperoxidase antibodies were negative.Abdominal and thyroid ultrasounds were normal. Left wrist X-ray revealed a bone age of 4 years.The brain MRI showed an ectopic neurohypophysis. The pituitary stalk was not seen.The patient started thyroid hormone replacement therapy and has been proposed for recombinant human growth hormone.Conclusion: This case emphasizes the need for a careful clinical and imagiologic investigation in children presenting with signs of pituitary hormone deficiency. Early diagnosis can prevent further evolution and complications of hypopituitarism.

A Japanese trichothiodystrophy patient with XPD mutations

Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by sulfur-deficient brittle hair complicated with ichthyosis, physical and mental retardation, and proneness to infections. Approximately half of TTD patients exhibit cutaneous photosensitivity because of the defect of nucleotide excision repair. Three genes, XPB, XPD and TTDA, have been identified as causative genes of photosensitive TTD. These three genes are components of basal transcription factor IIH. Most TTD cases have been reported in Europe and North America. We report a severely affected Japanese TTD patient with XPD mutations. Interestingly, his father has ichthyotic skin. The alteration in the paternal allele was a nucleotide substitution leading to Arg-722 to Trp (R722W), as previously reported in TTD patients. The other alteration in the maternal allele was a novel 3-bp deletion at nucleotides 67-69, resulting in the deletion of Ser-23, which is located upstream of helicase motif I and is the closest to the N-terminal end of XPD in reported mutations. The expression study showed that the two alterations were causative mutations for TTD. In Asia, it is likely that there are TTD patients who have not been diagnosed.

Analysis of osteoarthritis in a mouse model of the progeroid human DNA repair syndrome trichothiodystrophy

The increasing average age in developed societies is paralleled by an increase in the prevalence of many age-related diseases such as osteoarthritis (OA), which is characterized by deformation of the joint due to cartilage damage and increased turnover of subchondral bone. Consequently, deficiency in DNA repair, often associated with premature aging, may lead to increased pathology of these two tissues. To examine this possibility, we analyzed the bone and cartilage phenotype of male and female knee joints derived from 52- to 104-week-old WT C57Bl/6 and trichothiodystrophy (TTD) mice, who carry a defect in the nucleotide excision repair pathway and display many features of premature aging. Using micro-CT, we found bone loss in all groups of 104-week-old compared to 52-week-old mice. Cartilage damage was mild to moderate in all mice. Surprisingly, female TTD mice had less cartilage damage, proteoglycan depletion, and osteophytosis compared to WT controls. OA severity in males did not significantly differ between genotypes, although TTD males had less osteophytosis. These results indicate that in premature aging TTD mice age-related changes in cartilage were not more severe compared to WT mice, in striking contrast with bone and many other tissues. This segmental aging character may be explained by a difference in vasculature and thereby oxygen load in cartilage and bone. Alternatively, a difference in impact of an anti-aging response, previously found to be triggered by accumulation of DNA damage, might help explain why female mice were protected from cartilage damage. These findings underline the exceptional segmental nature of progeroid conditions and provide an explanation for pro- and anti-aging features occurring in the same individual.

Acquired nonscarring diffuse hair loss in a 3-year-old girl

A 3-year-old girl showed fine, sparse, and brittle scalp hair without signs of cicatricial cutaneous alterations. Dermoscopy as well as scanning electron microscopy revealed elliptical nodes as well as constricted regions along the hair shaft.

Brittle hair, developmental delay, neurologic abnormalities, and photosensitivity in a 4-year-old girl

MRI: magnetic resonance imaging NIH: National Institutes of Health TTD: trichothiodystrophy XP: xeroderma pigmentosum CASE SUMMARY History A 4-year-old Caucasian girl presented to the National Institutes of Health (NIH) for evaluation of sparse brittle hair, developmental delay, poor growth, recurrent infections, and photosensitivity (Fig 1 and Table I). The patient was born preterm at 35 weeks after a pregnancy complicated by elevated maternal alpha-fetoprotein at 16 weeks and pregnancy-induced hypertension beginning at 26 weeks. At birth, her skin showed generalized erythroderma and she was described as having a collodion membrane (Fig 1, A) that resolved over 2.5 weeks. By 1 month of age, the patient was reported to have congenital ichthyosis and mild scaling on her scalp, trunk, and lower extremities. By 23 months, she was reported to sunburn with minimal sun exposure and sweat very little in hot environments. Short brittle hair, nail spooning, head tremor (titubation), and asymmetric horizontal nystagmus were also noted. The patient did not sit unassisted until 12 months and did not crawl until 22 months.

Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation

Hair-nail ectodermal dysplasia (HNED; OMIM 602032) constitutes a rare subgroup of ectodermal dysplasias characterised by onychodystrophy, hypotrichosis and brittle hair. We identified a large consanguineous Pakistani family with four siblings affected by a congenital autosomal recessive form of the disease. Based on previous genetic findings in HNED we performed linkage analysis in the family using chromosome 12 markers. A genetic linkage analysis revealed a lod score of 2.92 ( = 0.0) at locus D12S368, indicating the disease gene to be located on chromosome 12. Candidate genes on chromosome 12, including the KRTHB5 gene and four additional keratin II genes, were sequenced in affected family members. Sequence analysis of the coding regions of keratin KRTHB5 gene, previously associated with a distinct clinical form of hair-nail dysplasia, revealed normal coding regions. Our study confirms linkage of a variant clinical form of hair-nail ectodermal dysplasia to chromosome 12 without any mutation in the coding sequences of the KRTHB5 gene. The results suggest this family to have either a non-coding mutation in the KRTHB5 gene, or a mutation in a yet unknown gene within the linked region on chromosome 12.

Two siblings with Netherton syndrome

Netherton syndrome (NS) is a rare genodermatosis characterized by autosomal recessive inheritance pattern, unknown etiology, ichthyosiform cutaneous changes, atopic diathesis, and alterations in the hair shaft. As a result of aging coupled with immune deficiency, clinical symptoms may vary. Herein, we present 2 siblings with the characteristic cutaneous symptoms of NS, albeit with some differences between the siblings. Materials and methods: Two sisters presented to our clinic with sparse and brittle hair along with pruritic, erythematous, and scaling cutaneous lesions. Both patients underwent a clinical examination and laboratory analyses. Results: Based on the clinical and laboratory findings, both patients were diagnosed with Netherton syndrome. Conclusion: The cases were reported because of the rarity of the disorder and simultaneous occurrence in 2 siblings, while aiming to highlight the variable nature of the clinical manifestations

Trichothiodystrophy with Dysmyelination and Central Osteosclerosis

Trichothiodystrophy (TTD) is a rare group of autosomal recessive disorders of DNA repair unified by the presence of sulfur-deficient brittle hair. We report a 3-year-old boy with classic clinical features of TTD, including ichthyosis, alopecia, developmental delay, and tiger-tail banding of the hair shaft on polarizing microscopy. Brain MR imaging showed both diffuse dysmyelination and osteosclerosis, findings that, in combination, may be specific for TTD.

Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH

Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by brittle hair and also associated with various systemic symptoms. Approximately half of TTD patients exhibit photosensitivity, resulting from the defect in the nucleotide excision repair. Photosensitive TTD is due to mutations in three genes encoding XPB, XPD and p8/TTDA subunits of the DNA repair/transcription factor TFIIH. Mutations in these subunits disturb either the catalytic and/or the regulatory activity of the two XPB, XPD helicase/ATPases and consequently are defective in both, DNA repair and transcription. Moreover, mutations in any of these three TFIIH subunits also disturb the overall architecture of the TFIIH complex and its ability to transactivate certain nuclear receptor-responsive genes, explaining in part, some of the TTD phenotypes.

Isolated Trypsin and Chymotrypsin Deficiency in a 2 Year Old Male

Purpose: Isolated trypsin and chymotrypsin deficiency is a very rare cause of poor growth and malabsorption. Pancreatic insufficiency is the inability of the exocrine pancreas to produce and transport enough digestive enzymes for proper digestion and absorption. This can be the result of progressive pancreatic damage that may be caused by cystic fibrosis (CF), Shwachman-Diamond Syndrome, acute or chronic pancreatitis, and type 1 or autoimmune diabetes. Pancreatic insufficiency symptoms include malnutrition, malabsorption, steatorrhea, bulky stools, abdominal pain, flatulence, vitamin deficiencies, and failure to thrive. A useful indirect test for severe pancreatic insufficiency is Fecal Pancreatic elastase-1 (FE1), a proteolytic pancreatic enzyme, which binds to bile salts, and does not degenerate in the intestine. However, a secretin stimulation test is required for mild pancreatic insufficiency, since it has a higher sensitivity. We describe a two year old, full term male, with poor weight gain, eczema, and bloody diarrhea on presentation. Initially, he was diagnosed with cow's milk and soy protein allergy. Elemental formula was commenced which resolved the bloody diarrhea. However, he still continued to have rashes, poor growth, steatorrhea, and brittle hair. He also developed iron deficiency anemia and low vitamin D levels. He had abnormal qualitative fecal fat on two consecutive tests. FE1 was normal, and he underwent an endoscopy with secretin stimulation. Biopsies did not show any abnormal pathology; however, the pancreatic fluid showed isolated trypsin and chymotrypsin deficiency with an alkaline pH. Sweat chloride collection was normal. CF, Shwachman-Diamond, and Pearson syndrome were ruled out. His signs and symptoms improved on iron, vitamins, and pancreatic enzyme supplementation. In conclusion, isolated trypsin and chymotrypsin deficiency is an uncommon cause of poor growth and malabsorption, which can be successfully diagnosed with a secretin stimulation test. Successful treatment can be accomplished with pancreatic enzyme supplementation, iron, and vitamins.

Sabinas syndrome in monozygotic twins

A pair of 2-year-old female monozygotic twins presented with short and brittle hair. There was marked reduction in hair density, and excessive curving of the eyelashes. Onychodystrophy was also evident. They also had developmental delay in verbal and motor skills. Neither their parents nor other relatives were known to be affected, and there was no history of consanguinity. Examination of the hair shaft under light microscopy showed trichoschisis, which was more evident under electron microscopy. Under polarized light, the hair shafts showed the pathognomonic 'tiger-tail' pattern. The level of sulphur in the hair was low. Both patients were negative for TTDN1 mutation. Clinical correlation was performed and the diagnosis of Sabinas syndrome was made. Sabinas syndrome is a very rare autosomal recessive disorder first described in a group of patients from a small community in north-eastern Mexico. It is diagnosable at birth, and its major symptoms include brittle hair, mental retardation and nail dysplasia. Structural hair abnormalities are seen by both light and electron microscopy.

Strict sun protection results in minimal skin changes in a patient with xeroderma pigmentosum and a novel c.2009delG mutation in XPD (ERCC2)

We examined the clinical, molecular and genetic features of a 16-year-old boy (XP2GO) with xeroderma pigmentosum (XP) and progressive neurological symptoms. The parents are not consanguineous. Increased sun sensitivity led to the diagnosis of XP at 2 years of age and a strict UV protection scheme was implemented. Besides recurrent conjunctivitis and bilateral pterygium, only mild freckling was present on his lips. He shows absent deep tendon reflexes, progressive sensorineural deafness and progressive mental retardation. MRI shows diffuse frontal cerebral atrophy and dilated ventricles. Symptoms of trichothiodystrophy (brittle hair with a tiger-tail banding pattern on polarized microscopy) or Cockayne syndrome (cachectic dwarfism, cataracts, pigmentary retinopathy and spasticity) were absent. XP2GO fibroblasts showed reduced post-UV cell survival (D(37) = 3.8 J/m(2)), reduced nucleotide excision repair, reduced expression of XPD mRNA and an undetectable level of XPD protein. Mutational analysis of the XPD gene in XP2GO revealed two different mutations: a common p.Arg683Trp amino acid change (c.2047C>T) known to be associated with XP and a novel frameshift mutation c.2009delG (p.Gly670Alafs*39). The latter mutation potentially behaves as a null allele. While not preventing neurological degeneration, early diagnosis and rigorous sun protection can result in minimal skin disease without cancer in XP patients.

The effects of biotin supplementation on serum and liver tissue biotinidase enzyme activity and alopecia in rats which were administrated to valproic acid

Valproic acid (VPA) is a widely used and well-tolerable antiepileptic drug in epileptic patients. However, VPA has many side effects dose-dependent or non-dose-dependent. It is reported that VPA treatment may lead to biotin deficiency and low serum and liver tissue biotinidase enzyme activity (BEA). Major clinical manifestations in biotin deficiency are seborrheic dermatitis, dry skin, fine and brittle hair, and alopecia. We aimed to investigate the effects of biotin supplementation on serum and liver tissue BEA and alopecia during VPA therapy. Rats were randomly divided into 4 groups, each consisted of 15 rats (VPA-B1, VPA-B2, VPA, and control). Except the control group, all groups were administrated VPA dose of 600 mg/kg/d per oral (PO) for 60 days with 12 h intervals two divided doses. VPA-B1 was administrated biotin dose of 6 mg/kg/d and VPA-B2 was administrated biotin dose of 0.6 mg/kg/d. In the third week of the study, we determined alopecia in the study groups. Alopecia was seen in the subjects of 13.3% of VPA-B1 ( n = 2), 13.3% of VPA-B2 ( n = 2), and 40% of VPA ( n = 6). But statistical significant effect on alopecia by biotin supplementation was not able to be determined between the study groups. In the control group, alopecia was not observed. The ratios of alopecia in the study groups were statistically higher than the control group ( p = 0.028). Itchiness was more obvious in the study groups compared with the control group. Serum biotin levels of the biotin supplemented groups (VPA-B1 and VPA-B2) were higher than the other groups (VPA and control group). Serum biotin levels of the VPA group were lower than the control group. There were significant decreaeses in the levels of serum and liver tissue BEA of the study groups compared with the control group. In conclusion we showed that VPA usage reduced the serum and liver tissue BEA and impaired the biotin utilization by affecting the liver. Partial biotinidase deficiency may lead to alopecia. It might be prevented by biotin supplementation in the patients receiving VPA therapy. We considered that further studies are necessary to find out the effective and safe biotin dose.

Copper Trafficking and Extracellular Superoxide Dismutase Activity

In 1962, Menkes et al1 first described a pediatric disorder characterized by hypopigmented brittle hair, doughy skin, connective tissue fragility, failure to thrive, progressive neurological damage, and various defects of the arterial wall. This was termed “kinky hair syndrome” and later was found to be associated with a disturbance in copper metabolism due to mutations in the ATP7A gene. The ATP7A (or Menkes ATPase) is 1 of 2 membrane-bound copper-transporting ATPases (ATP7A and ATP7B) essential for controlling intracellular copper homeostasis. ATP7A is of particular importance for the transfer of copper through the membrane of the trans-Golgi network and hence is important for the so-called secretory pathway of copper.2 In Menkes syndrome, in which the function of the ATP7A transporter is disturbed, systemic copper levels are low because copper export from enterocytes is greatly impaired and copper thus accumulates in the intestine. A critical manifestation of impaired ATP7A function is the limited incorporation of copper, an essential catalytic residue in a variety of enzymes. An early example of this defect was highlighted by insufficient insertion of copper into the tyrosinase of patients with Menkes disease.3 Tyrosinase is the rate-limiting enzyme of melanin formation with defects in its activity leading to low melanin levels in skin, albinism, and the hypopigmentation that is a clinical hallmark of Menkes syndrome. The study by Qin et al,4 published in the current issue of Hypertension , is of interest and significance because a critical linkage has been made between cardiovascular function and the biochemical defects in copper trafficking that are a hallmark of altered ATP7A function. Qin …

Defective Transcription/Repair Factor IIH Recruitment to Specific UV Lesions in Trichothiodystrophy Syndrome

Most trichothiodystrophy (TTD) patients present mutations in the xeroderma pigmentosum D (XPD) gene, coding for a subunit of the transcription/repair factor IIH (TFIIH) complex involved in nucleotide excision repair (NER) and transcription. After UV irradiation, most TTD/XPD patients are more severely affected in the NER of cyclobutane pyrimidine dimers (CPD) than of 6-4-photoproducts (6-4PP). The reasons for this differential DNA repair defect are unknown. Here we report the first study of NER in response to CPDs or 6-4PPs separately analyzed in primary fibroblasts. This was done by using heterologous photorepair; recombinant adenovirus vectors carrying photolyases enzymes that repair CPD or 6-4PP specifically by using the energy of light were introduced in different cell lines. The data presented here reveal that some TTD/XPD mutations affect the recruitment of TFIIH specifically to CPDs, but not to 6-4PPs. This deficiency is further confirmed by the inability of TTD/XPD cells to recruit, specifically for CPDs, NER factors that arrive in a TFIIH-dependent manner later in the NER pathway. For 6-4PPs, we show that TFIIH complexes carrying an NH(2)-terminal XPD mutated protein are also deficient in recruitment of NER proteins downstream of TFIIH. Treatment with the histone deacetylase inhibitor trichostatin A allows the recovery of TFIIH recruitment to CPDs in the studied TTD cells and, for COOH-terminal XPD mutations, increases the repair synthesis and survival after UV, suggesting that this defect can be partially related with accessibility of DNA damage in closed chromatin regions.