Comparing the responses of countries and National Health Systems to the COVID-19 pandemic: a critical analysis with a case-report series.

This review aimed to compare the different responses of countries to the pandemic, their National Health Systems, and their impact on citizens' health. This work aimed to create a narrative plot that connects different discussion points and suggests organizational solutions and strategic choices in the face of the pandemic. In particular, this work focused on public health organizations, specifically the European Union and vaccination politics. It is also based on a case report series (about the United States, Germany, Vietnam, New Zealand, Cuba, and Italy), where each country has responded differently to the pandemic in terms of political decisions such as vaccination type, information to citizens, dealings with independent experts, and other specific country factors. In comparing the various models of care systems response to the pandemic, it emerges that: we have found some (few) good practices, but without global coordination, and this is obviously not enough. It is now quite clear that there cannot be a "good answer" in a single nation. Uncoordinated local responses cannot counter a global phenomenon. The second point is that the general context must be considered from a strategic point of view. With the threat of new pandemics (but also of health disasters linked to climate change, pollution, and wars), humanity finds itself at the crossroads between investing in a "democratic" management of international bodies but without power (and at the mercy of the need for funds with consequent conflicts) or in some new leadership proposals that advocate efficiency and problem-solving (and that would probably be able to implement it) but that would place processes totally outside of the public's control.

Direct-acting antivirals used in HCV-related liver disease do not affect thyroid function and autoimmunity.

PURPOSE: It is well known that interferon-α (IFN-α), used for long time as the main therapy for HCV-related disease, induces thyroid alterations, but the impact of the new direct-acting antivirals (DAAs) on thyroid is not established. Aim of this prospective study was to evaluate if DAAs therapy may induce thyroid alterations. METHODS: A total of 113 HCV patients, subdivided at the time of the enrollment in naïve group (n = 64) and in IFN-α group (n = 49) previously treated with pegylated interferon-α and ribavirin, were evaluated for thyroid function and autoimmunity before and after 20-32 weeks of DAAs. RESULTS: Before starting DAAs, a total of 8/113 (7.1%) patients showed Hashimoto's thyroiditis (HT) all belonging to IFN-α group (8/49, 16.3%), while no HT cases were found in the naïve group. Overall, 7/113 (6.2%) patients were hypothyroid: 3/64 (4.7%) belonging to naïve group and 4/49 (8.2%) to IFN-α group. Furthermore, a total of 8/113 patients (7.1%) showed subclinical hyperthyroidism: 2/64 (3.1%) were from naïve group and 6/49 (12.2%) from IFN-α group. Interestingly, after DAAs therapy, no new cases of HT, hypothyroidism and hyperthyroidism was found in all series, while 6/11 (54.5%) patients with non-autoimmune subclinical thyroid dysfunction became euthyroid. Finally, the only association between viral genotypes and thyroid alterations was genotype 1 and hypothyroidism. CONCLUSIONS: This study supports evidence that DAAs have a limited or missing influence on thyroid in patients with HCV-related diseases. Moreover, it provides preliminary evidence that subclinical non-autoimmune thyroid dysfunction may improve after HCV infection resolution obtained by DAAs.

Modulation of hypersensitivity to oxidative DNA damage in ATM defective cells induced by potassium bromate by inhibition of the Poly (ADP-ribose) polymerase (PARP).

The ataxia telangiectasia mutated (ATM) protein is a pivotal multifunctional protein kinase predominantly involved in DNA damage response, as well as in maintaining overall functional integrity of the cells. Apart from playing its major role in regulating the cellular response to DNA damage, ATM, when mutated, can additionally determine oxidative stress, metabolic syndrome, mitochondrial dysfunction and neurodegeneration. In the present paper we aim to investigate the levels of oxidative stress potentially induced by the oxidizing rodent renal carcinogen KBrO3 in ATM-defective lymphoblastoid cell lines (LCLs) established from four classical AT patients (with different ATM mutations), one AT variant with reduced hypersensitivity to X rays, obligate AT heterozygotes and wild type intrafamilial control. A possible modulatory involvement of PARP in potentially induced oxidative stress is also evaluated following its inhibition with 3-aminobenzamide (3-AB). Treatments with KBrO3 clearly showed a marked hypersensitivity of the ATM-defective LCLs, including the AT variant. A marked and statistically significant reduction of KBrO3-induced chromosomal damage following inhibition of PARP by 3-AB, was observed in all AT LCLs, but not in those from the AT variant, AT heterozygotes and wild type intrafamilial control. This result is suggestive of a modulatory involvement of PARP in the hypersensitivity of ATM-defective cells to DNA oxidative damage.

Distribution of IL28B Polymorphism in a Cohort of Italians and Immigrants with HCV Infection: Association with Viraemia, Stage of Fibrosis and Response to Treatment.

Aims of the study are to investigate, in a cohort of patients affected by HCV chronic hepatitis with genotypes 1 and 4, the prevalence of interleukin 28B (IL28B) genotypes, the possible association between IL28B polymorphism and severity of liver damage, the role of IL28B CC as a predictor of outcome. 365 patients with HCV infection were observed between 2013 and 2014. Demographic, virological, biochemical, and genetic characteristics of each patient were investigated. Liver fibrosis was assessed by transient elastometry. Mean age of the patients (72.9 % males, 27.1 % females) is 50 years. 91.5 % % of patients are Caucasian, 8.5 % African. In the patients with HCV1 and HCV4 a higher frequency of IL28B CT is observed with a prevalence of 52.1 and 61.8 % respectively. As regards ethnic group, African people have a prevalence of 35.5 % for CC, while Caucasians have a prevalence of 23.8 % for CC. In our cohort, IL28B polymorphism does not show significant differences among ethnic groups and in HCV1 and HCV4 genotypes. As described in literature, IL28B CC genotype is confirmed as predictor of sustained virological response in both Caucasians and Africans. A significant correlation between liver fibrosis and IL28B polymorphism emerges.

Targeting transcription-coupled nucleotide excision repair overcomes resistance in chronic lymphocytic leukemia.

Treatment resistance becomes a challenge at some point in the course of most patients with chronic lymphocytic leukemia (CLL). This applies to fludarabine-based regimens, and is also an increasing concern in the era of more targeted therapies. As cells with low-replicative activity rely on repair that triggers checkpoint-independent noncanonical pathways, we reasoned that targeting the nucleotide excision repair (NER) reaction addresses a vulnerability of CLL and might even synergize with fludarabine, which blocks the NER gap-filling step. We interrogated here especially the replication-independent transcription-coupled-NER ((TC)-NER) in prospective trial patients, primary CLL cultures, cell lines and mice. We screen selected (TC)-NER-targeting compounds as experimental (illudins) or clinically approved (trabectedin) drugs. They inflict transcription-stalling DNA lesions requiring TC-NER either for their removal (illudins) or for generation of lethal strand breaks (trabectedin). Genetically defined systems of NER deficiency confirmed their specificity. They selectively and efficiently induced cell death in CLL, irrespective of high-risk cytogenetics, IGHV status or clinical treatment history, including resistance. The substances induced ATM/p53-independent apoptosis and showed marked synergisms with fludarabine. Trabectedin additionally perturbed stromal-cell protection and showed encouraging antileukemic profiles even in aggressive and transforming murine CLL. This proof-of-principle study established (TC)-NER as a mechanism to be further exploited to resensitize CLL cells.

53BP1 represses mitotic catastrophe in syncytia elicited by the HIV-1 envelope.

p53 binding protein-1 (53BP1) participates in checkpoint signaling during the DNA damage response (DDR) and during mitosis. In this study we report that 53BP1 aggregates in nuclear foci within syncytia elicited by the human immunodeficiency virus (HIV)-1 envelope. 53BP1 aggregation occurs as a consequence of nuclear fusion (karyogamy (KG)). It colocalizes partially with the promyelomonocytic leukemia protein (PML), and the ataxia telangiectasia mutated kinase (ATM), the two components of the DDR that mediate apoptosis induced by the HIV-1 envelope. ATM-dependent phosphorylation of 53BP1 on serines 25 and 1778 (53BP1S25P and 53BP1S1778P) occurs at these DNA damage foci. 53BP1S25P was also detected in syncytia present in the lymph nodes or frontal brain sections from HIV-1-infected carriers, as well as in peripheral blood mononucleated cells from HIV-1-infected individuals, correlating with viral load. Knockdown of 53BP1 caused HIV-1 envelope-induced syncytia to enter abnormal mitoses, leading to their selective destruction through mitochondrion-dependent and caspase-dependent pathways. In conclusion, depletion of 53BP1 triggers the demise of HIV-1-elicited syncytia through mitotic catastrophe.

Role of alpha7-nicotinic acetylcholine receptor in human non-small cell lung cancer proliferation.

OBJECTIVES: Lung cancer is the most common cause of cancer death in the world. Cigarette smoking represents the major risk factor. Nicotine, an active component of cigarettes, can induce cell proliferation, angiogenesis and apoptosis resistance. All these events are mediated through the nicotinic acetylcholine receptor (nAChR) expressed on lung cancer cells. We speculate that new insights into the pathophysiological roles of nAChR may lead to new therapeutic avenues to reduce non-small cell lung cancer (NSCLC) tumour growth. MATERIALS AND METHODS: Human samples of NSCLC, cell lines and mouse models were utilized in Western blotting, reverse transcriptase polymerase chain reaction and apoptosis studies. RESULTS: Human NSCLC tissues expressed alpha7-nAChR. This expression was higher in smoking patients with squamous carcinomas than those with adenocarcinomas and in male smoking patients than in females. All the data support the hypothesis that major expression of alpha7-nAChR is related to major activation of the Rb-Raf-1/phospho-ERK/phospho-p90RSK pathway. alpha7-nAChR antagonists, via mitochondria associated apoptosis, inhibited proliferation of human NSCLC primary and established cells. Nicotine stimulates tumour growth in a murine model, A549 cells orthotopically grafted. The effects of nicotine were associated with increases in phospho-ERK in tumours. Proliferation effects of nicotine could be blocked by inhibition of alpha7-nAChR by the high affinity ligand alpha-cobratoxin. CONCLUSION: These results showed that alpha7-nAChR plays an important role in NSCLC cell growth and tumour progression as well as in cell death.

Treatment of chronic hepatitis D.

Despite recent advances in the treatment of chronic viral hepatitis, therapy of chronic hepatitis D is not yet satisfactory. The only option currently available is interferon-alpha (IFN), whose efficacy is related to the dose and duration of treatment. However, the rate of sustained hepatitis D virus (HDV) clearance after a 1-year course with high doses of standard IFN is low. Better results have recently been reported with pegylated IFN both in IFN-naïve and in previous nonresponders to standard IFN, suggesting the use of pegylated IFN as a first-line therapy in chronic hepatitis D. Nucleoside analogues that inhibit hepatitis B virus (HBV) are ineffective against HDV and combination therapy with lamivudine or ribavirin has not shown significant advantages over monotherapy with either standard or pegylated IFN. Because the ultimate goal of treatment is eradication of both HDV and HBV, in responders IFN therapy should be continued as long as possible until the loss of hepatitis B surface antigen, adjusting the dose to patient tolerance. However, because side-effects are common, continuous monitoring is mandatory. Although the first results obtained with pegylated IFN have been encouraging, the rate of sustained virological response is still low and the rate of relapse high, emphasizing the need for developing novel classes of antivirals specifically interfering with the life cycle of this unique virus.

Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study.

BACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients. OBJECTIVE: To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families. METHODS: The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations. RESULTS: All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation). CONCLUSIONS: The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin.

XK-aprosencephaly and related entities.

We offer further biological characterization of the XK atelen/aprosencephaly syndrome in two infants, one with prolonged survival, the other presenting prenatally with apparent hydranencephaly and an orbital tumor (OS). Familial occurrence in the former born to presumably nonconsanguineous Lybian parents may represent parental germinal mosaicism or autosomal recessive inheritance. Both had apparently normal chromosomes; however, the Lybian infant had slightly increased induced chromosome breakage suggesting that this rare multiple congenital anomalies syndrome may involve a DNA repair defect. Virtual absence of atelen/aprosencephalic structures may lead to an arthrogryposis-like prenatal movement disorder. The orbital tumor in the Utah infant consisted of dystopic neural tissue compressing a rudimentary globe and was connected by a thin bridge of neural tissue to the small mass of disorganized brain tissue usually found in atelen/aprosencephalic infants and fetuses. No evidence of an encephaloclastic process was found in the autopsied Utah infant.

The novel human gene aprataxin is directly involved in DNA single-strand-break repair.

The cells of an ataxia-oculomotor apraxia type 1 (AOA1) patient, homozygous for a new aprataxin mutation (T739C), were treated with camptothecin, an inhibitor of DNA topoisomerase I which induces DNA single-strand breaks. DNA damage was evaluated by cytogenetic analysis of chromosomal aberrations. The results obtained showed marked and dose-related increases in induced chromosomal aberrations in the patient and her heterozygous mother compared to the intrafamilial wild-type control. The alkaline comet assay confirmed this pattern. Moreover, the AOA1 cells did not show hypersensitivity to ionizing radiation, i.e. X-rays. These findings clearly indicate the direct involvement of aprataxin in the DNA single-strand-break repair machinery.

[Cystic lymphangioma of the adult: our experience and review of literature]. / Linfangioma cistico dell'adulto: nostra esperienza e revisione della letteratura.

Cystic lymphangioma is an uncommon benign pathology, usually reported in children, rarely in adult. Its embryopathogenesis is still controversial: it seems to arise from the lymphatic vessels, mainly in the cervico-cranial district. It is macroscopically characterised by multiple cystic non-communicating concamerations. Definitive diagnosis used to be intraoperative and was usually an unexpected finding. Nowadays, with modern imaging technologies, CT and MRI, diagnosis can be assumed before intervention even though certain diagnosis can still be reached only with histological examination. Imaging techniques can help for a precise mapping of the lesion and definition of its limits with the other structures, improving therapeutic success. Various therapeutical options are reported in literature, but complete surgical excision is still considered the best approach and the most successful. The Authors report their experience and review the literature on cystic lymphangioma in adult.

Chk2 activation dependence on Nbs1 after DNA damage.

The checkpoint kinase Chk2 has a key role in delaying cell cycle progression in response to DNA damage. Upon activation by low-dose ionizing radiation (IR), which occurs in an ataxia telangiectasia mutated (ATM)-dependent manner, Chk2 can phosphorylate the mitosis-inducing phosphatase Cdc25C on an inhibitory site, blocking entry into mitosis, and p53 on a regulatory site, causing G(1) arrest. Here we show that the ATM-dependent activation of Chk2 by gamma- radiation requires Nbs1, the gene product involved in the Nijmegen breakage syndrome (NBS), a disorder that shares with AT a variety of phenotypic defects including chromosome fragility, radiosensitivity, and radioresistant DNA synthesis. Thus, whereas in normal cells Chk2 undergoes a time-dependent increased phosphorylation and induction of catalytic activity against Cdc25C, in NBS cells null for Nbs1 protein, Chk2 phosphorylation and activation are both defective. Importantly, these defects in NBS cells can be complemented by reintroduction of wild-type Nbs1, but neither by a carboxy-terminal deletion mutant of Nbs1 at amino acid 590, unable to form a complex with and to transport Mre11 and Rad50 in the nucleus, nor by an Nbs1 mutated at Ser343 (S343A), the ATM phosphorylation site. Chk2 nuclear expression is unaffected in NBS cells, hence excluding a mislocalization as the cause of failed Chk2 activation in Nbs1-null cells. Interestingly, the impaired Chk2 function in NBS cells correlates with the inability, unlike normal cells, to stop entry into mitosis immediately after irradiation, a checkpoint abnormality that can be corrected by introduction of the wild-type but not the S343A mutant form of Nbs1. Altogether, these findings underscore the crucial role of a functional Nbs1 complex in Chk2 activation and suggest that checkpoint defects in NBS cells may result from the inability to activate Chk2.

hMRE11: genomic structure and a null mutation identified in a transcript protected from nonsense-mediated mRNA decay.

We showed recently that mutation of the hMRE11 gene identified a new ataxia telangiectasia-like disorder (ATLD). In this report we describe the genomic organization of the hMRE11 gene and the analysis of a promoter region that appears to direct the divergent transcription of hMRE11 and the adjacent gene. The characterization of the genomic organization of the hMRE11 gene allowed us to determine the basis of an apparent null hMRE11 allele present in the mother and two patients in one of our two ATLD families. Polymorphic markers in the hMRE11 gene, including the promoter region, provided evidence that the mutated maternal allele was not deleted. An exon by exon search revealed the presence of a missense mutation in exon 15, the effect of which was to create a premature termination codon. Transcripts derived from the mutant allele were found to be subject to nonsense-mediated mRNA decay (NMD). Therefore, this allele was effectively null, because little if any mRNA from it was available for translation. The ATLD patients carrying this protein-truncating hMRE11 mutation have survived because the null allele they inherited from their mother is present with a missense mutation inherited from their father, which is expressed as normal levels of partially functional MRE11 protein. The mutation in the maternal hMRE11 allele of family 2 was also identified in a further unrelated Italian family with ATLD and also found to be subject to NMD.

Efficient DNA base excision repair in ataxia telangiectasia cells.

Ataxia telangiectasia (A-T) cells are sensitive to a broad range of free-radical-producing and alkylating agents. Damage caused by such agents is in part repaired by base excision [base excision repair (BER)]. Two BER pathways have been demonstrated in mammalian cells: a single-nucleotide-insertion pathway and a long-patch pathway involving resynthesis of 2-10 nucleotides. Although early studies failed to detect DNA-repair defects in A-T cells exposed to ionizing radiation and radiomimetic agents, more recent experiments performed in non-dividing A-T cells and the demonstrated interaction of the A-T-mutated protein (ATM) with the BRCA1 gene product suggest that a DNA-repair defect may underlie, at least in part, the radiation sensitivity in A-T cells. We have analysed BER of a single abasic site or a single uracil in two A-T families, using an in vitro BER system. In both families, the mutation involved was homozygous and completely inactivated the ATM protein. No difference was observed between affected individuals and heterozygous or homozygous wild-type relatives in their capacity to perform DNA repair by either one-nucleotide insertion or the long-patch pathway. Hence, the putative DNA-repair defect in A-T cells, if any, does not involve BER.

ATM protein and p53-serine 15 phosphorylation in ataxia-telangiectasia (AT) patients and at heterozygotes.

ATM (ataxia-telangiectasia mutated) gene plays a central role in the DNA-damage response pathway. We characterized the ATM protein expression in immortalized cells from AT and AT-variant patients, and heterozygotes and correlated it with two ATM-dependent radiation responses, G1 checkpoint arrest and p53-Ser 15 phosphorylation. On Western blots, the full-length ATM protein was detected in eight of 18 AT cases, albeit at 1-32% of the normal levels, whereas a truncated ATM protein was detected in a single case, despite the prevalence among cases of truncation mutations. Of two ataxia without telangiectasia [A-(T)] cases, one expressed 20% and the other approximately 70% of the normal ATM levels. Noteworthy, among ten asymptomatic heterozygous carriers for AT, normal amounts of ATM protein were found in one and reduced by 40-50% in the remaining cases. The radiation-induced phosphorylation of p53 protein at serine 15, largely mediated by ATM kinase, was defective in AT, A(-T) and in 2/4 heterozygous carriers, while the G1 cell cycle checkpoint was disrupted in all AT and A(-T) cases, and in 3/10 AT heterozygotes. Altogether, our study shows that AT and A(-T) cases bearing truncation mutations of the ATM gene can produce modest amounts of full-length (and only rarely truncated) ATM protein. However, this limited expression of ATM protein provides no benefit regarding the ATM-dependent responses related to G1 arrest and p53-ser15 phosphorylation. Our study additionally shows that the majority of AT heterozygotes express almost halved levels of ATM protein, sufficient in most cases to normally regulate the ATM-dependent DNA damage-response pathway.

Ataxia-telangiectasia: phenotype/genotype studies of ATM protein expression, mutations, and radiosensitivity.

Previous studies on a limited number of ataxia-telangiectasia (A-T) patients with detectable levels of intracellular ATM protein have suggested a genotype/phenotype correlation. We sought to elucidate this possible correlation by comparing ATM protein levels with mutation types, radiosensitivity, and clinical phenotype. In this study, Western blot analysis was used to measure ATM protein in lysates of lymphoblastoid cell lines (LCLs) from 123 unrelated A-T patients, 10 A-T heterozygotes, and 10 patients with phenotypes similar to A-T. Our Western blot protocol can detect the presence of ATM protein in as little as 1 microg of total protein; at least 25 microg of protein was tested for each individual. ATM protein was absent in 105 of the 123 patients (85%); most of these patients had truncating mutations. The remaining subset of 18 patients (15%) had reduced levels of normal-sized ATM protein; missense mutations were more common in this subset. We used a colony survival assay to characterize the phenotypic response of the LCLs to radiation exposure; patients with or without detectable ATM protein were typically radiosensitive. Nine of 10 A-T heterozygotes also had reduced expression of ATM, indicating that both alleles contribute to ATM protein production. These data suggest that although ATM-specific mRNA is abundant in A-T cells, the abnormal ATM protein is unstable and is quickly targeted for degradation. We found little correlation between level of ATM protein and the type of underlying mutation, the clinical phenotype, or the radiophenotype.

Changes of chromatin condensation in one patient with ataxia telangiectasia disorder: a structural study.

Differential scanning calorimetry and quantitative fluorescence microscopy have been employed to characterize the structure and organization of in situ chromatin in lymphoblastoid cells obtained from one ataxia telangiectasia (A-T) patient and one healthy family member. The proven capability of these biophysical techniques to measure changes of chromatin condensation directly inside the cells makes them very powerful in studying the eventual structural changes associated with the appearance of a pleiotropic genetic disorder such as ataxia telangiectasia. A-T syndrome is genetically heterogeneous and can be induced by different mutations of a single gene. The aim of this work is to determine whether the genetic mutation exhibited by the A-T patient of this study may be associated with modifications of chromatin structure and organization. Both the calorimetric and the fluorescence microscopy results acquired on cells from the A-T patient show that the structure and distribution of nuclear chromatin in situ change considerably with respect to the control. A significant decondensation of the nuclear chromatin is in fact associated with the appearance of the A-T disorder in the A-T patient under analysis, together with a rearrangement of the chromatin domains inside the nucleus.

Molecular prenatal diagnosis of ataxia telangiectasia heterozygosity by direct mutational assays.

Ataxia telangiectasia (AT) is a severe autosomal recessive disease, rare but not infrequent in Italy. Owing to the seriousness of the disease, prenatal diagnosis has been attempted in the past by means of cytogenetic, biochemical, radio-biological and indirect molecular analyses. We performed the first direct molecular prenatal diagnosis of AT on a chorionic villi sample from a 37-year-old woman at the 10th week of pregnancy. She had two previous children suffering AT and two induced abortions. At molecular analysis her affected children were compound heterozygotes for mutations 7792C-->T in exon 55 (from the mother) and 8283delTC in exon 59 (from the father). The prenatal diagnosis was performed by two different operators in double-blind form. Mutation 7792C-->T was studied by restriction enzyme analysis using TaqI. Mutation 8283delTC was screened by heteroduplex analysis. The fetus was heterozygous for the mutation 7792C-->T (confirmed by sequencing). In order to verify the possible contamination by maternal DNA, polymorphic loci HLA-DRB1 and HLA-DQA1, together with microsatellite markers D6S259, D11S2000, D11S29, D11S1778 and D11S2179, were examined. All these loci were informative, showing that the fetus received only one allele from each parent. The heterozygosity for ATM mutation 7792C-->T was confirmed by molecular studies after the birth of a healthy male baby.