Breast cancer local recurrence after mastectomy with immediate latissimus dorsi myocutaneous flap reconstruction: A case report.

Even though most local recurrences after autologous breast reconstruction occur in superficial tissue, they also occur in deep tissue in the reconstructed breast. A 49-year-old woman presented with a bloody discharge from the right nipple. Ultrasonography revealed a hypoechoic area in her right breast, which was diagnosed as ductal carcinoma in situ on histopathology. We performed nipple-sparing mastectomy and immediate reconstruction of the breast with a latissimus dorsi myocutaneous flap. At 6 years postoperatively, the patient presented with a palpable mass. Ultrasonography revealed a solid mass lesion subcutaneously in the right breast. Computed tomography revealed multiple enhanced solid mass lesions in the subcutaneous and deep tissues of the reconstructed breast. The mass in the deep tissue of the reconstructed breast was diagnosed as an invasive micropapillary carcinoma by biopsy. For local recurrence, we performed wide excision of the reconstructed breast. The masses in the subcutaneous and deep tissues of the reconstructed breast were diagnosed as invasive micropapillary carcinoma. Superficial recurrence was first detected by physical examination, and deep recurrence was later detected with further imaging. We present a case of local recurrences that occurred in the deep tissue, in addition to superficial tissue of the reconstructed breast.

A Rare Case of 18F-FDG Uptake in an Ectopic Thyroid Carcinoma of the Anterior Middle Neck Lacking Thyroglossal Duct Remnants.

An 80-year old female presented with a well-defined tumor of the anterior middle neck, and a diagnosis of thyroglossal duct cyst was made. When the tumor size increased, malignancy was suspected. Ultrasonography revealed a smooth, heterogeneously hypoechoic area at her anterior neck. Contrast-enhanced computed tomography showed a well-defined contrast-enhanced tumor inferior to the hyoid bone. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed a fluorine-18 fluorodeoxyglucose-avid tumor with a maximum standardized uptake value of 12.8. Surgical tumor resection was performed, and the histopathological finding was ectopic papillary carcinoma lacking thyroglossal duct remnants, which is very rare. To our knowledge, few cases of ectopic thyroid carcinoma with 18F-FDG PET/CT findings have been reported. Ectopic thyroid carcinoma lacking thyroglossal duct remnants should be considered a differential diagnosis in cases of 18F-FDG uptake in an anterior middle neck tumor.

PI3K/Akt/mTOR signalling pathway activation in patients with ER-positive, metachronous, contralateral breast cancer treated with hormone therapy.

Oestrogen receptor (ER)-positive, metachronous, contralateral breast cancer (MCBC) sometimes develops during or soon after completion of hormone therapy (HT), but it is uncertain whether it is HT-resistant. We examined the association between ER-positive second cancer and activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways, which are associated with HT resistance. We examined the treatment-free interval (time after completion of HT for initial cancer) in 41 patients with ER-positive MCBC with a history of adjuvant HT for initial cancer (HT group), and initial-to-second period duration (time after operation of initial cancer to onset of second cancer) in 17 patients with ER-positive MCBC in whom adjuvant HT was not applied to the initial tumour (control group or no HT group). Phosphorylated S6 (pS6) and phosphorylated MAPK (pMAPK) were used as indicators of PI3K/Akt/mTOR and MAPK pathway activity, respectively. Tumours were classified as showing negative, positive or strongly positive staining, and the correlation between staining and treatment-free interval or initial-to-second period duration was evaluated using the Spearman's rank correlation coefficient (ρ). Treatment-free interval and pS6 staining showed a negative correlation (ρ=-0.5355; P=0.0003) in the HT group. There was no correlation between initial-to-second period duration and pS6 staining in the no HT group (ρ=-0.0814; P=0.756). There was no correlation between pMAPK signalling and the treatment-free interval in the HT group (ρ=-0.1560; P=0.330) or the initial-to-second period duration in the no HT group (ρ=-0.0116; P=0.965). Development of a second ER-positive cancer during or soon after completion of HT for the initial cancer may be associated with activation of the PI3K/Akt/mTOR pathway. Care should be taken during follow-up and when selecting adjuvant therapy for second cancer.

Ocular manifestations of xeroderma pigmentosum: long-term follow-up highlights the role of DNA repair in protection from sun damage.

OBJECTIVE: Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by mutations in DNA repair genes. Clinical manifestations of XP include mild to extreme sensitivity to ultraviolet radiation resulting in inflammation and neoplasia in sun-exposed areas of the skin, mucous membranes, and ocular surfaces. This report describes the ocular manifestations of XP in patients systematically evaluated in the Clinical Center at the National Institutes of Health. DESIGN: Retrospective observational case series. PARTICIPANTS: Eighty-seven participants, aged 1.3 to 63.4 years, referred to the National Eye Institute (NEI) for examination from 1964 to 2011. Eighty-three patients had XP, 3 patients had XP/Cockayne syndrome complex, and 1 patient had XP/trichothiodystrophy complex. METHODS: Complete age- and developmental stage-appropriate ophthalmic examination. MAIN OUTCOME MEASURES: Visual acuity; eyelid, ocular surface, and lens pathology; tear film and tear production measures; and cytologic analysis of conjunctival surface swabs. RESULTS: Of the 87 patients, 91% had at least 1 ocular abnormality. The most common abnormalities were conjunctivitis (51%), corneal neovascularization (44%), dry eye (38%), corneal scarring (26%), ectropion (25%), blepharitis (23%), conjunctival melanosis (20%), and cataracts (14%). Thirteen percent of patients had some degree of visual axis impingement, and 5% of patients had no light perception in 1 or both eyes. Ocular surface cancer or a history of ocular surface cancer was present in 10% of patients. Patients with an acute sunburning skin phenotype were less likely to develop conjunctival melanosis and ectropion but more likely to develop neoplastic ocular surface lesions than nonburning patients. Some patients also showed signs of limbal stem cell deficiency. CONCLUSIONS: Our longitudinal study reports the ocular status of the largest group of patients with XP systematically examined at 1 facility over an extended period of time. Structural eyelid abnormalities, neoplasms of the ocular surface and eyelids, tear film and tear production abnormalities, ocular surface disease and inflammation, and corneal abnormalities were present in this population. Burning and nonburning patients with XP exhibit different rates of important ophthalmologic findings, including neoplasia. In addition, ophthalmic characteristics can help refine diagnoses in the case of XP complex phenotypes. DNA repair plays a major role in protection of the eye from sunlight-induced damage.

Negative support of significant others affects psychological adjustment in breast cancer patients.

Significant others play an important role in providing support in patients' lives, but some types of support negatively affect the patients. This study was conducted in early-stage breast cancer patients to examine the structure of support, which was provided by their significant others and assessed negatively by the patients, and to identify negative support relating to the psychological adjustment of these patients. Thus, we first conducted interviews among 28 breast cancer patients to identify these support items assessed as negative; next, we conducted a questionnaire survey using the resulting items in 109 postoperative patients who had early-stage breast cancer. We performed exploratory and confirmatory factor analyses and obtained a valid second-order factor structure, including superordinate factors (excessive engagement, avoidance of problems and underestimation) and subordinate factors (overprotection, encouragement and management). Among these factors, the avoidance of problems was the only factor to be negatively associated with psychological adjustment of the patients, suggesting that these patients receive problem-avoiding support. The results of our study suggest that such problem-avoiding support from significant others can be counter-productive and potentially worsen the psychological adjustment of breast cancer patients.

Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair.

BACKGROUND: The frequency of cancer, neurologic degeneration and mortality in xeroderma pigmentosum (XP) patients with defective DNA repair was determined in a four decade natural history study. METHODS: All 106 XP patients admitted to the National Institutes of Health from 1971 to 2009 were evaluated from clinical records and follow-up. RESULTS: In the 65 per cent (n=69) of patients with skin cancer, non-melanoma skin cancer (NMSC) was increased 10,000-fold and melanoma was increased 2000-fold in patients under age 20. The 9 year median age at diagnosis of first non-melanoma skin cancer (NMSC) (n=64) was significantly younger than the 22 year median age at diagnosis of first melanoma (n=38)-a relative age reversal from the general population suggesting different mechanisms of carcinogenesis between NMSC and melanoma. XP patients with pronounced burning on minimal sun exposure (n=65) were less likely to develop skin cancer than those who did not. This may be related to the extreme sun protection they receive from an earlier age, decreasing their total ultraviolet exposure. Progressive neurologic degeneration was present in 24% (n=25) with 16/25 in complementation group XP-D. The most common causes of death were skin cancer (34%, n=10), neurologic degeneration (31%, n=9), and internal cancer (17%, n=5). The median age at death (29 years) in XP patients with neurodegeneration was significantly younger than those XP patients without neurodegeneration (37 years) (p=0.02). CONCLUSION: This 39 year follow-up study of XP patients indicates a major role of DNA repair genes in the aetiology of skin cancer and neurologic degeneration.

Relationship between thymidylate synthase (TYMS) gene polymorphism and TYMS protein levels in patients with high-risk breast cancer.

The thymidylate synthase gene (TYMS) has three functional polymorphisms which are associated with TYMS expression. To explore the predictability of TYMS polymorphisms for the sensitivity and toxicity of 5-fluorouracil (5-FU) in breast cancer patients, this study investigated the association between TYMS polymorphisms and TYMS protein expression in normal and tumour tissue specimens from 49 lymph node-positive breast cancer patients. An analysis of the TYMS 3'-UTR polymorphism showed that level of TYMS protein in normal tissue with the +6 bp/+6 bp genotype was significantly higher than that for the -6 bp/+6 bp genotype. Tumour tissue with the +6 bp/+6 bp genotype had a significantly higher TYMS protein expression than did those with other genotypes. These findings suggest that breast cancer patients with the TYMS 3'-UTR +6 bp/+6 bp polymorphism whose tumours show a 6 bp deletion within TYMS 3'-UTR represent a group that may derive the most benefit from 5-FU chemotherapy.

Discrimination between worry and anxiety among cancer patients: development of a Brief Cancer-Related Worry Inventory.

OBJECTIVES: A psychometric scale for assessing cancer-related worry among cancer patients, called the Brief Cancer-Related Worry Inventory (BCWI), was developed. METHODS: A cross-sectional questionnaire survey for item development was conducted of 112 Japanese patients diagnosed with breast cancer, and test-retest validation analysis was conducted using the data from another prospective study of 20 lung cancer patients. The questionnaire contained 15 newly developed items for cancer-related worry, the Hospital Anxiety and Depression Scale, The Impact of Event Scale Revised, and the Medical Outcomes Study Short Form-8. RESULTS: Exploratory factor analysis of the 15 items yielded a 3-factor structure including (1) future prospects, (2) physical and symptomatic problems and (3) social and interpersonal problems. A second-order confirmatory factor analysis identified a second-order factor called cancer-related worry and confirmed the factor structure with an acceptable fit (chi-square (df=87)=160.16, P=0.001; GFI=0.83; CFI=0.92; RMSEA=0.09). The internal consistency and test-retest reliability were confirmed with the lung cancer sample. Multidimensional scaling found that cancer-related worry is separate from anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms. CONCLUSION: Our study succeeded in developing and confirming the validity and reliability of a BCWI. The study also confirmed the discriminable aspects of cancer-related worry from anxiety, depression, and PTSD symptoms.

Xeroderma pigmentosum-variant patients from America, Europe, and Asia.

Xeroderma pigmentosum-variant (XP-V) patients have sun sensitivity and increased skin cancer risk. Their cells have normal nucleotide excision repair, but have defects in the POLH gene encoding an error-prone polymerase, DNA polymerase eta (pol eta). To survey the molecular basis of XP-V worldwide, we measured pol eta protein in skin fibroblasts from putative XP-V patients (aged 8-66 years) from 10 families in North America, Turkey, Israel, Germany, and Korea. Pol eta was undetectable in cells from patients in eight families, whereas two showed faint bands. DNA sequencing identified 10 different POLH mutations. There were two splicing, one nonsense, five frameshift (3 deletion and 2 insertion), and two missense mutations. Nine of these mutations involved the catalytic domain. Although affected siblings had similar clinical features, the relation between the clinical features and the mutations was not clear. POLH mRNA levels were normal or reduced by 50% in three cell strains with undetectable levels of pol eta protein, indicating that nonsense-mediated message decay was limited. We found a wide spectrum of mutations in the POLH gene among XP-V patients in different countries, suggesting that many of these mutations arose independently.

Hematoma-directed and ultrasound-guided breast-conserving surgery for nonpalpable breast cancer after Mammotome biopsy.

Stereotactic vacuum-assisted (Mammotome) breast biopsy is a powerful diagnostic tool for detecting microcalcifications on mammography, but it is difficult to remove the targeted lesion precisely when subsequent breast-conserving surgery is to be carried out. We achieved satisfactory results by performing hematoma-directed breast-conserving surgery after stereotactic Mammotome biopsy in seven patients. To identify the exact location of the Mammotome biopsy during the breast-conserving surgery, we created an iatrogenic hematoma in the biopsy cavity using patient's blood. This hematoma was detected easily on intraoperative ultrasonography in all patients, and was palpable as a soft mass in five of the seven patients. The microcalcifications were completely removed in all patients, and no cancer cells were found in the margin surfaces after breast-conserving surgery. There were no complications during the injection of the patient's blood into the biopsy cavity or during the hematoma-directed surgery. We describe this new procedure of hematoma-directed breast-conserving surgery following Mammotome biopsy for nonpalpable cancer with microcalcifications.

Molecular analysis of DNA polymerase eta gene in Japanese patients diagnosed as xeroderma pigmentosum variant type.

POLH mutations were identified in 16 Japanese patients, who were diagnosed, both clinically and at a cellular level, as being of the xeroderma pigmentosum variant type (XPV). While all the patients developed skin cancer with an average onset of the cancer at 45 years, in non-XP Japanese the onset was at over 70 years. All the cell strains from the patients were normal or slightly hypersensitive to UV and most of these showed enhanced UV sensitivity when the post-UV colony formation was performed in the presence of caffeine. Immunoprecipitation analysis with two kinds of anti-POLH protein antibodies revealed that cells from 13 patients did not show the 83 kDa POLH band and that cells from one patient had a faint 83 kDa band. All of these 14 cell strains, without a POLH band or with a weak POLH band, had mutations in the POLH gene. The IP analysis of the POLH protein revealed a very useful method for screening the patients suspected of XPV. Seven mutations in the POLH gene including three novel mutations were identified. Among the mutations detected, 11 alleles out of 28 (39%) were G490T mutations.

Health-related quality of life in breast cancer: A cross-cultural survey of German, Japanese, and South Korean patients.

PURPOSE: The aim of this study was to evaluate health-related quality of life (HRQOL) in breast cancer patients across countries, and to cross-culturally examine the impact of psychosocial factors on HRQOL. PATIENTS AND METHODS: A total of 413 women with breast cancer from Germany (n = 195), Japan (n = 112), and Korea (n = 106) completed a survey assessing HRQOL and HRQOL-related factors. HRQOL was measured using the Short-Form Health Survey (SF-8). Measures of psychological distress (Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised), coping (Dealing with Illness Inventory-German Revised), and social support (Illness-Specific Social Support Scale-German Revised) were included. RESULTS: The effect of the factor country on physical QOL was seen to be significant, but small (P = 0.049, ES = 0.018). The scales of General Health (P = 0.023), Vitality (P = 0.004), and Role Emotional (P = 0.003) differed across countries, with the South Korean patients having lower scores compared to the German and Japanese patients. The nature of the impact of psychosocial factors on HRQOL did not differ greatly across countries except with regard to avoidance, however, the degree to which these factors influence HRQOL did differ greatly. Overall, depression, depressive coping, and problematic support showed a strong detrimental effect on the HRQOL of breast cancer patients. CONCLUSIONS: Results from this study suggest that strategies which target an improvement of HRQOL in cancer patients should also consider the patients' cultural and healthcare system contexts. Interventions are needed to improve detrimental psychosocial factors.

Quantitative analysis of the reconstructed breast using a 3-dimensional laser light scanner.

Postoperative cosmesis of the reconstructed breast depends on the interrelation of shape, size (volume), and symmetry. In this study, reconstructed breasts were analyzed with 3-dimensional projections generated by laser light scanning. Fifty-one cases of breast reconstruction following mastectomy (16 cases of rectus abdominis flap, 15 cases of latissimus dorsi flap, and 20 cases of tissue expansion) were evaluated 6 months postoperatively. Shape, volume, and symmetry were quantitatively evaluated. Captured images of the normal breast were mirror-reversed and superimposed on images of the reconstructed breast. Differences in the generated Moire patterns were used to quantitatively compare breasts. The method was rapid, reproducible, and accurate in comparison to thermoplaster casts. It was found that rectus abdominis flaps applied following total mastectomy and latissimus dorsi flaps applied following partial mastectomy gave the best results for their relatively low degree of asymmetry. Application of tissue expansion led to greater asymmetry and poorer overall cosmesis. In conclusion, a 3-dimensional laser light scanning system makes it possible to quantitate the cosmetic outcome following breast reconstruction.

Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients.

Xeroderma pigmentosum group C (XP-C) is a rare autosomal recessive disorder. Patients with two mutant alleles of the XPC DNA repair gene have sun sensitivity and a 1000-fold increase in skin cancers. Clinically normal parents of XP-C patients have one mutant allele and one normal allele. As a step toward evaluating cancer risk in these XPC heterozygotes we characterized cells from 16 XP families. We identified 15 causative mutations (5 frameshift, 6 nonsense and 4 splicing) in the XPC gene in cells from 16 XP probands. All had premature termination codons (PTC) and absence of normal XPC protein on western blotting. The cell lines from 26 parents were heterozygous for the same mutations. We employed a real-time quantitative reverse transcriptase-PCR assay as a rapid and sensitive method to measure XPC mRNA levels. The mean XPC mRNA levels in the cell lines from the XP-C probands were 24% (P<10(-7)) of that in 10 normal controls. This reduced XPC mRNA level in cells from XP-C patients was caused by the PTC that induces nonsense-mediated mRNA decay. The mean XPC mRNA levels in cell lines from the heterozygous XP-C carriers were intermediate (59%, P=10(-4)) between the values for the XP patients and the normal controls. This study demonstrates reduced XPC mRNA levels in XP-C patients and heterozygotes. Thus, XPC mRNA levels may be evaluated as a marker of cancer susceptibility in carriers of mutations in the XPC gene.

Clinical experience of weekly paclitaxel-based treatment as preoperative chemotherapy for patients with primary breast cancer.

BACKGROUND: Paclitaxel is an effective agent in the treatment of metastatic breast cancer. The aim of this study was to evaluate the safety and efficacy of weekly paclitaxel-based preoperative chemotherapy in patients with large operable breast cancer. METHODS: Patients initially received paclitaxel as a 3-hour infusion at 175 mg/m2. Three weeks after initial administration, two cycles of three weeks of paclitaxel 80 mg/m2 over a 1 hour infusion followed by a one week break were given. Of 22 patients, 9 had stage II (tumor diameter greater than 3 cm), 4 stage III A, 7 stage III B, and 2 stage IV (with ipsilateral supraclavicular lymph node metastasis) cancer, respectively. RESULTS: Excluding stage IV patients, the overall response rate to paclitaxel chemotherapy was 80%. Four of the 20 patients (20%) showed a clinical complete response (cCR). Two of these showed pathologic complete response and the other 2 had only the ductal component remaining. The primary tumor response and axillary lymph node downstaging following preoperative chemotherapy tended to be related in 16 patients with clinically positive nodes. Breast conserving surgery was performed as a result of downstaging in the 9 stage II patients. Grade 3 neutropenia occurred in one patient when 175 mg/m2 of paclitaxel was administered, but no serious side effects developed during the weekly administration of paclitaxel. CONCLUSION: The use of weekly paclitaxel-based preoperative chemotherapy appears to yield a significant anti-tumor effect without inducing serious drug-related adverse effects. Furthermore, the effectiveness of this treatment appears to result in a higher frequency of breast conserving surgery.

Two essential splice lariat branchpoint sequences in one intron in a xeroderma pigmentosum DNA repair gene: mutations result in reduced XPC mRNA levels that correlate with cancer risk.

The lariat branch point sequence (BPS) is crucial for splicing of human nuclear pre-mRNA yet BPS mutations have infrequently been reported to cause human disease. Using an inverse RT-PCR technique we mapped two BPS to the adenosine residues at positions -4 and -24 in intron 3 of the human XPC DNA repair gene. We identified homozygous mutations in each of these BPS in two newly diagnosed Turkish families with the autosomal recessive disorder xeroderma pigmentosum (XP). Cells from two severely affected children in family A harbor a homozygous point mutation in XPC intron 3 (-9 T to A), located within the downstream BPS. Using a real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) assay, these cells expressed no detectable (<0.1%) normal XPC message. Instead they expressed an XPC mRNA isoform with deletion of exon 4 that has no DNA repair activity in a host cell reactivation (HCR) assay. In contrast, in cells from three mildly affected siblings in family B, the BPS adenosine located at the -24 position in XPC intron 3 is mutated to a G. Real-time QRT-PCR revealed 3-5% of normal XPC message. These cells from family B had a higher level of HCR than cells from the severely affected siblings in family A, who had multiple skin cancers. Mutations identified in two BPS of the XPC intron 3 resulted in alternative splicing that impaired DNA repair function, thus implicating both of these BPS as essential for normal pre-mRNA splicing. However, a small amount of normal XPC mRNA can provide partial protection against skin cancers.

The human XPC DNA repair gene: arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function.

XPC DNA repair gene mutations result in the cancer-prone disorder xeroderma pigmentosum. The XPC gene spans 33 kb and has 16 exons (82-882 bp) and 15 introns (0.08-5.4 kb). A 1.6 kb intron was found within exon 5. Sensitive real- time quantitative reverse transcription-polymerase chain reaction methods were developed to measure full-length XPC mRNA (the predominant form) and isoforms that skipped exons 4, 7 or 12. Exon 7 was skipped in approximately 0.07% of XPC mRNAs, consistent with the high information content of the exon 7 splice acceptor and donor sites (12.3 and 10.4 bits). In contrast, exon 4 was skipped in approximately 0.7% of the XPC mRNAs, consistent with the low information content of the exon 4 splice acceptor (-0.1 bits). A new common C/A single nucleotide polymorphism in the XPC intron 11 splice acceptor site (58% C in 97 normals) decreased its information content from 7.5 to 5.1 bits. Fibroblasts homozygous for A/A had significantly higher levels (approximately 2.6-fold) of the XPC mRNA isoform that skipped exon 12 than those homozygous for C/C. This abnormally spliced XPC mRNA isoform has diminished DNA repair function and may contribute to cancer susceptibility.

Relationship of neurologic degeneration to genotype in three xeroderma pigmentosum group G patients.

We studied three newly diagnosed xeroderma pigmentosum complementation group G patients with markedly different clinical features. An Israeli-Palestinian girl (XP96TA) had severe abnormalities suggestive of the xeroderma pigmentosum/Cockayne syndrome complex including sun sensitivity, neurologic and developmental impairment, and death by age 6 y. A Caucasian girl (XP82DC) also had severe sun sensitivity with neurologic and developmental impairment and died at 5.8 y. In contrast, a mildly affected 14-y-old Caucasian female (XP65BE) had sun sensitivity but no neurologic abnormalities. XP96TA, XP82DC, and XP65BE fibroblasts showed marked reductions in post-ultraviolet cell survival and DNA repair but these were higher in XP65BE than in XP82DC. XP96TA fibroblasts had very low XPG mRNA expression levels whereas XP65BE fibroblasts had nearly normal levels. Host cell reactivation of an ultraviolet-treated reporter assigned all three fibroblast strains to the rare xeroderma pigmentosum complementation group G (only 10 other patients previously reported). XP96TA and XP82DC cells had mutations in both XPG alleles that are predicted to result in severely truncated proteins including stop codons and two base frameshifts. The mild XP65BE patient had an early stop codon mutation in the paternal allele. The XP65BE maternal allele had a single base missense mutation (G2817A, Ala874Thr) that showed residual ability to complement xeroderma pigmentosum complementation group G cells. These observations agree with earlier studies demonstrating that XPG mutations, which are predicted to lead to severely truncated proteins in both alleles, were associated with severe xeroderma pigmentosum/Cockayne syndrome neurologic symptoms. Retaining residual functional activity in one allele was associated with mild clinical features without neurologic abnormalities.