Constitutional epimutations of the MLH1 gene are an alternative cause of Lynch syndrome, in which inactivation of an allele of a mismatch repair (MMR) gene results from MLH1 promoter methylation, rather than a pathogenic genetic variant. These epimutations are often mosaic, and methylation levels ranging from ~50% monoallelic methylation to low-level methylation (1%-5%) are observed in the blood of MLH1 epimutation carriers. Using a specific and highly sensitive droplet digital methyl-specific PCR (ddMSP) assay, six patients with very low methylation levels (< 1%) were identified in a series of 142 patients with a MLH1-methylated tumor diagnosed before age 61, who had been referred to the clinical lab between 2020 and 2024. These patients were initially missed by standard pyrosequencing assay, emphasizing the need for highly sensitive assays for constitutional epimutation screening. To confirm that methylated DNA molecules detected by ddMSP did not correspond to circulating tumor DNA rather than germline DNA, multiple validation analyses were performed, including validation of the constitutional origin of methylation on other sources of germline DNA and tumoral analysis. Taking into account the other patients identified as epimutation carriers by pyrosequencing during the same 5-year period, 13.1% of patients with a MLH1-methylated tumor before age 61 were diagnosed as Lynch syndrome patients, which changed their clinical follow-up. These findings highlight the relevance of recommendations for systematic MLH1 epimutation screening using highly sensitive assays in patients with MLH1-methylated tumors diagnosed before age 61. Such screening will increase the number of patients diagnosed with Lynch syndrome caused by a MLH1 constitutional epimutation, improving patient care and outcomes, as well as genetic counseling.

Background The impact of insulin-resistance on bone mineral density (BMD) remains unclear. Sclerostin inhibits bone formation, and increases with ageing, metabolic syndrome, and renal failure. Genetically-determined low sclerostin levels are associated with high BMD. Our aim was to determine the bone phenotype and the influence of insulin-resistance without obesity on sclerostin levels in Familial Partial Lipodystrophy type 2 (FPLD2). Methods Demographic, metabolic, anthropometric, and bone parameters were compared after adjustment on age and menopausal status across four groups of women (19 FPLD2, 12 obese with diabetes, 14 obese without diabetes, 11 lean controls). Results The FPLD2 group had significantly higher Intra-Abdominal/Total-Abdominal Fat (IAF/TAF) ratio and lower fat mass percentage compared to the other groups. Glucose parameters (Fasting blood glucose, C-peptide, HbA1c, HOMA2-IRCP), and triglycerides were significantly higher in the FPLD2 group than in controls, with a higher sclerostin level. Sclerostin levels were positively associated with age, glucose parameters, Z-score, T-score, and negatively with osteocalcin. FPLD2 was the only subgroup in which the association between sclerostin and HOMA2-IRCP was maintained. In contrast, osteocalcin levels were negatively associated with age, glucose parameters, triglycerides, IAF/TAF, and bone parameters. Neither sclerostin or osteocalcin were associated with BMI, whole-body fat, or leptin. Conclusion The association of sclerostin (positive) and osteocalcin (negative) with HOMA2-IRCP, but not with fat mass parameters, suggests a predominant role of insulin-resistance over fat mass in the regulation of osteokines. Insulin-resistance may uncouple the usual relationship between sclerostin and BMD. The sclerostin contribution in early atherosclerosis in FPLD2 remains to be studied.

INTRODUCTION:Genome sequencing (GS) is reshaping newborn screening (NBS) by enabling the early detection of a broader range of rare, treatable and/or actionable disorders. In the context of rapid therapeutic advances, international pilot programs - many coordinated within the International Consortium on Newborn Sequencing (ICoNS) - are evaluating genome-based NBS (gNBS) as a preventive public health strategy. MATERIALS AND METHODS:We reviewed published international gNBS pilot studies, with particular attention to discussions related to endocrine disorders. We integrated insights from the French PERIGENOMED-CLINICS 1 (PGC1) project, including its curated gene list and collaboration mainly with the FIRENDO French network dedicated to rare endocrine diseases. RESULTS:No publications were identified specifically addressing gNBS in rare pediatric endocrine diseases as a unified domain. In comparative analyses of gNBS pilot programs, endocrine disorders represented approximately 10% of included conditions, with marked heterogeneity across initiatives and no primary endocrine disorder uniformly retained. Analysis of the PGC1 dataset identified 125 endocrine and endocrine-adjacent gene-disease dyads (14% of all project dyads), divided into list 1 ("treatable", n=62) and list 2 ("actionable", n=63). List 1 predominantly included early-onset, hormonally driven disorders, whereas list 2 extended toward obesity-related and multisystem syndromic conditions. Stratification by clinical actionability revealed four categories ranging from time-critical neonatal conditions to surveillance-driven and long-term risk phenotypes, underscoring substantial variability in timing of intervention, penetrance, and level of evidence supporting early benefit. CONCLUSION:Genomic NBS is transforming rare disease management, including endocrine diseases, by enabling earlier diagnosis, precision care, and coordinated professional and family-based interventions, marking a paradigm shift in population health.

CONTEXT:Klinefelter syndrome (KS), defined by a 47, XXY karyotype, is commonly associated with progressive testicular failure. The precise timing of Sertoli and Leydig cell dysfunction during puberty remains unclear. OBJECTIVE:To determine the onset and progression of testicular insufficiency during puberty in KS, and to assess whether diagnostic timing (prenatal vs postnatal) impacts pubertal phenotype. METHODS:We conducted a retrospective, single-centre study of 57 patients with KS aged 9-25 years, followed from the prepubertal period at Lille University Hospital. Longitudinal clinical and hormonal data were analysed according to pubertal stage rather than chronological age. RESULTS:All patients entered puberty spontaneously at a physiological age (mean 12.6 years), but experienced a slow pubertal tempo (mean duration: 4.08 years). Sertoli cell dysfunction appeared within 12 months of pubertal onset, with rising FSH and declining AMH and inhibin B levels. Inhibin B concentrations never reached the reference range for Tanner stage 5 and declined below the adult threshold (92 pg/mL) 2 years after pubertal onset. Leydig cell dysfunction, defined by elevated LH and low-normal testosterone, emerged after 36 months. At puberty completion, 94% had Sertoli cell insufficiency (i.e. FSH level > 7.19 IU/L) and 80% had Leydig cell insufficiency (LH > 5.88 IU/L). Postnatally diagnosed patients exhibited significantly higher LH (p = 0.03) and lower inhibin B (p = 0.01) levels. CONCLUSION:Testicular insufficiency in KS begins approximately 18 months after pubertal onset, with Sertoli cell failure preceding Leydig cell decline. Early diagnosis and longitudinal monitoring are essential to guide endocrine management and to support individualized counselling regarding fertility preservation strategies, which should be considered according to pubertal stage rather than chronological age.

BACKGROUND:Polycystic ovary syndrome (PCOS), recently renamed polyendocrine metabolic ovarian syndrome (PMOS), is characterised by neuroendocrine dysfunction with accelerated gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH) pulsatility driving hyperandrogenism and anovulatory infertility. METHODS:We used the prenatal anti-Müllerian hormone (AMH)-exposed PMOS-like mouse model (PAMH) and a phase I clinical trial in women with PMOS without obesity. PAMH and control mice received acute or intermittent low-dose Ganirelix, and oestrous cyclicity, ovulation, gonadotrophins, and steroids were assessed. In women, two subtherapeutic Ganirelix doses (0.025 mg, n = 8; 0.0625 mg, n = 10) were administered once in early follicular phase, with 10-min blood sampling over 8 h to quantify LH pulsatility and reproductive hormones. FINDINGS:In PMOS-like mice, a single Ganirelix injection normalised exaggerated LH pulsatility, and six-week intermittent treatment restored oestrous cyclicity, ovulation, and testosterone levels without affecting controls. In women with PMOS both Ganirelix doses reduced LH pulse frequency, basal, mean and total LH, and decreased the LH/FSH ratio. D4-androstenedione fell by 25-30% at both doses, AMH declined modestly at 0.0625 mg, while oestradiol remained unchanged. INTERPRETATION:Low-dose GnRH-receptor antagonism with Ganirelix can recalibrate, rather than suppress, GnRH/LH signalling, attenuating hyperandrogenism and, in mice, restoring ovulatory function. These data identify partial GnRHR blockade as a promising neuroendocrine-centred strategy in PMOS and provide a rationale for phase II trials evaluating repeated low-dose regimens, ovulatory restoration, and fertility outcomes. FUNDING:This work was supported by the European Research Council (ERC) Horizon-ERC-POC grant (ERC-2022-POC2, n° 101111874) and the French National Research Agency (ANR-24-CHBS-0002, France 2030).

OBJECTIVE:Advances in oncological and haematological treatments have markedly improved childhood survival, yet gonadotoxic therapies often compromise testicular function. Testicular tissue extraction (TTE) with cryopreservation is increasingly offered to prepubertal boys at high risk of infertility; however, data on long-term endocrine and fertility outcomes remain limited. This study evaluated the long-term endocrine and exocrine testicular function of males who underwent TTE prior to gonadotoxic therapy. DESIGN AND PATIENTS:This was a retrospective, observational, single-centre study including 50 males treated between 2009 and 2022 at Lille University Hospital (median age at TTE: 5.6 years; median age at last follow-up: 14.6 years). Underlying conditions comprised malignant haematological disorders (52%), non-malignant diseases (34%), and solid tumours (14%); 80% underwent allogeneic haematopoietic stem cell transplantation. MEASUREMENTS:Serial clinical assessments and biochemical markers of Leydig and Sertoli cell function (LH, FSH, testosterone, inhibin B, AMH) were recorded from puberty onset to young adulthood. Data were stratified by treatment intensity, pubertal timing, and disease type. Post-pubertal semen analysis was performed in consenting individuals. RESULTS:All participants experienced spontaneous pubertal onset. Sertoli cell dysfunction, evidenced by elevated FSH and persistently low inhibin B, was detectable early in puberty and persisted into adulthood. At Tanner stage 5, 18% had elevated LH, 75% elevated FSH, and 89% low inhibin B; comparable rates were observed in adulthood. Radiotherapy was associated with higher gonadotropin levels at equivalent chemotherapy doses, and Sertoli cell impairment was more pronounced in malignant disease and peri-pubertal treatment. Among 12 semen analyses, spermatozoa were detected in 42%, all in non-malignant cases without radiotherapy. CONCLUSIONS:Males undergoing TTE prior to gonadotoxic therapy frequently develop persistent Sertoli cell dysfunction, with limited fertility potential in many cases. These findings underscore the importance of systematic, long-term andrological surveillance and personalised fertility counselling in this high-risk population.

The impact of a germline BRCA1/2 pathogenic variant (gBRCApv) on baseline or late post-treatment AMH concentrations in breast cancer patients has been extensively studied, yielding mixed conclusions. However, whether the AMH decline during neo-adjuvant chemotherapy reflects differences in chemotherapy susceptibility between gBRCApv carriers and non-carriers remains unexplored. A monocentric, retrospective, longitudinal study was conducted on breast cancer patients carrying a gBRCApv (n = 12) or wild-type (WT) (n = 35) who received a neo-adjuvant sequential chemotherapy (CT) with anthracyclines followed by taxanes. Serum AMH levels were measured at baseline (AMH0) and at three time points during CT by a hypersensitive assay. Tumor size change was assessed via imaging. The impact of genetic status on AMH decline was evaluated using a linear mixed model with post hoc analysis. The change of AMH concentrations from baseline to the end of CT tended to be influenced by the genetic status (BRCA * time interaction, p = 0.058). The slope between AMH0 and the end of anthracyclines (after log transformation) was steeper in gBRCApv than in WT patients (mean (SE): − 5.54 (0.63) vs − 3.97 (0.62); p = 0.023). Tumor size change was positively and significantly correlated with the change in AMH levels (AMH MidCT-AMH0) in gBRCApv patients (r = 0.93, p < 0.001) but not in WT patients (r = − 0.05; p = 0.84). Germline BRCA1/2 status influences AMH decline during neo-adjuvant CT with drugs inducing DNA lesions. AMH decay is positively related to tumor size change assessed by imaging in gBRCApv patients. However, no conclusions can be drawn regarding the relationship with treatment response assessed by histological criteria.

BACKGROUND:Several putative susceptibility genes for familial papillary thyroid carcinoma, or familial non-medullary thyroid carcinoma (FNMTC), have been identified. However, in most families the molecular basis for FNMTC remains elusive. METHODS:Two families with≥3 first-degree relatives in≥2 generations and≥2 unaffected relatives were selected. Germline DNA from 2 patients and 2 unaffected individuals per family were analyzed by whole genome sequencing. All individuals were genotyped for putative pathogenic variants by Sanger sequencing, and minor allele frequency (MAF) was determined in 179 PTC-free European controls and the GnomAD database. Methylation analysis of candidate genes was carried out by EPIC BeadChips or pyrosequencing on germline and tumoral DNA. RESULTS:Heterozygous variants in cancer-related genes expressed in thyroid tissue and predicted to impact protein function were identified in patients from both families. In F8, the best candidate was the P2RX5 p.Leu32Gln variant previously reported in another PTC family. However, its relatively high MAF in European controls (0.43%) casts doubt on its pathogenic role. In F17, the most relevant variant was c.345del in MST1R encoding the tyrosine kinase receptor RON. The variant is predicted to encode a truncated isoform. Further analysis of tumor and germline DNA showed no clear evidence of an expression switch from the long to the short oncogenic RON isoform. CONCLUSION:Our data provide novel insight on the genetics of FNMTC. The P2RX5 p.Leu32Gln variant should be considered either as low-penetrant or not associated with PTC predisposition. MST1R appears as a new putative susceptibility gene for FNMTC that warrants further consideration.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

BackgroundThe von Hippel-Lindau (VHL) disease is a hereditary tumour syndrome caused by germline mutations in VHL tumour suppressor gene. The identification of VHL variants requires accurate classification which has an impact on patient management and genetic counselling.MethodsThe TENGEN (French oncogenetics network of neuroendocrine tumors) and PREDIR (French National Cancer Institute network for Inherited predispositions to kidney cancer) networks have collected VHL genetic variants and clinical characteristics of all VHL-suspected patients analysed from 2003 to 2021 by one of the nine laboratories performing VHL genetic testing in France. Identified variants were registered in a locus-specific database, the Universal Mutation Database-VHL database (http://www.umd.be/VHL/).ResultsHere we report the expert classification of 164 variants, including all missense variants (n=124), all difficult interpretation variants (n=40) and their associated phenotypes. After initial American College of Medical Genetics classification, first-round classification was performed by the VHL expert group followed by a second round for discordant and ambiguous cases. Overall, the VHL experts modified the classification of 87 variants including 30 variants of uncertain significance that were as (likely)pathogenic variants for 19, and as likely benign for 11.ConclusionConsequently, this work has allowed the diagnosis and influenced the genetic counselling of 45 VHL-suspected families and can benefit to the worldwide VHL community, through this review.

L’impact de l’insulino-résistance sur la masse osseuse reste incertain. La sclérostine inhibe la formation osseuse ostéoblastique et s’élève avec le vieillissement, le diabète, l’obésité et l’insuffisance rénale. Le but de cette étude était de déterminer l’influence de l’insulinorésistance sur la sclérostine sanguine, dans les FPLD2, un modèle d’insulino-résistance sans surpoids. Patients Quatre groupes de femmes ont été comparés : 19 FPLD2 (variant LMNA R482), 12 obèses diabétiques (OD), 15 obèses non diabétiques (OND) et 11 témoins sains minces (PHRC-2009_09/094). Méthodes Les marqueurs métaboliques, phosphocalcique, la leptine, le peptide-C, la sclérostine, le pourcentage de masse grasse (%MG) et le Z-score (DEXA), la masse grasse intra-abdominale (MGIA) et totale (IRM) ont été recueillis. Résultats L’âge ne différait pas entre les 4 groupes sauf chez les OD plus âgés que les FPLD2, sans différence entre les taux de sclérostine et créatinine. L’IMC, le %MG, la MGIA et le rapport MGIA/totale différaient entre les 4 groupes. Sclérostine, triglycérides et peptide-C étaient plus élevés chez les FPLD2 que chez les témoins, mais ne différaient pas des groupes obèses. La leptinémie était plus élevée dans les groupes obèses que FPLD2 et témoins. Dans toute la population, la sclérostine était positivement corrélée à l’âge, l’HbA1c, le Z-score, la MGIA, les triglycérides et le peptide-C. Conclusion La sclérostine était corrélée aux marqueurs biologiques d’insulino-résistance, à la graisse viscérale, mais également au Z-score. Dans les FPLD2, les valeurs élevées de sclérostine n’étaient pas associées à une ostéoporose, peut-être en raison de l’insulino-résistance qui augmente l’ostéocalcine.

Alpha-1 antitrypsin (A1AT) is the major circulating serine protease inhibitor. Hypersialylated glycoforms (HSG) are produced to boost A1AT anti-inflammatory and anti-protease properties. Their occurrence and prognostic impact outside severe COVID-19 or community-acquired pneumonia are unknown. Our aim was to clarify the occurrence of A1AT functional deficiency and HSG in patients admitted into intensive care unit (ICU) for any cause. A1AT and elastase inhibitory capacity (EIC) were measured in serum. Functional A1AT deficiency was defined by a measured EIC/calculated EIC Ratio ≤0.85. HSG were identified by isoelectrofocusing and quantified by gel densitometry. A total of 248 serum samples was analyzed, 173 from COVID-19 and 75 from non COVID-19 patients. A functional A1AT deficiency occurred 3-fold more frequently in non-COVID-19 than in COVID-19 patients: 18.7 % vs 6.9 % and was not associated with more frequent S/Z deficient alleles. Functional deficiency was also more frequent in deceased than alive patients in COVID-19 group. M0 and M1 HSG of A1AT occurred in around half of patients but the relative proportion of M1 significantly increased in deceased vs alive patients only in the non-COVID-19 group explaining the absence of worsening of the functional deficiency. In conclusion, our study shows that a functional A1AT deficiency is more frequently observed in patients admitted to the ICU for a cause unrelated to COVID-19, as well as in those with an unfavorable evolution. Among the latter, only those admitted for non-COVID-19 tried to compensate the functional deficiency by increasing the proportion of M1 HSG of A1AT.

Introduction Les FPLD sont des maladies rares caractérisées par un déficit partiel de graisse sous-cutanée entraînant un syndrome métabolique, les 2 principaux gènes en cause étant LMNA (FPLD2) et PLIN1 (FPLD4). L’objectif de cette étude était de comparer le phénotype de ces 2 types de FPLD. Méthodes Dans une cohorte prospective (NCT01784289), les données cliniques, métaboliques, le % de masse grasse (DEXA), la graisse intra-abdominale, abdominale totale et le % de stéatose hépatique (IRM), la NF et l’immunophénotypage lymphocytaire ont été comparés entre 4 groupes de patients (20 minces, 20 obèses non-diabétiques, 26 FPLD2 (LMNA-R482) et 8 FPLD4. Résultats Les groupes FPLD2 et FPLD4 présentaient un IMC, graisse intra-abdominale, HbA1c, triglycérides, ALAT, % stéatose hépatique et éosinophiles plus élevés que le groupe mince. Les groupes FPLD2 et 4 ne différaient que par une leptinémie significativement plus faible chez les FPLD4. Par rapport aux témoins minces, les leucocytes et les neutrophiles étaient augmentés et les NK diminués chez les FPLD2. Les basophiles étaient augmentés chez les FPLD4 comparés aux témoins minces et obèses. Dans toute la population, les basophiles étaient corrélés positivement aux paramètres métaboliques, et négativement au % de masse grasse et à la leptinémie. Conclusion Cette première étude comparant le phénotype des FPLD 2 et 4 à des témoins montre un phénotype similaire des FPLD2 et 4. Les variations des lymphocytes NK et des basophiles, cellules-clés impliquées dans la réponse Th2, suggèrent l’intérêt de cibler les basophiles avec des traitements tels que l’omalizumab dans ces maladies orphelines.

Ovarian tissue cryopreservation (OTC) is recommended by scientific societies for women undergoing highly gonadotoxic cancer treatments. Following transplantation, the restoration of ovarian function is typically characterised by the resumption of spontaneous menstruation. Yet, a few studies have looked at the longitudinal hormonal variations following transplantation. This study aims to investigate the fluctuation of gonadotropins and granulosa/theca cells secretions during the interval between ovarian transplantation and the recovery of menstrual function in two young women with no residual ovarian activity. We selected two patients diagnosed with Hodgkin’s lymphoma, initially referred for OTC at the ages of 19 and 15, respectively, and who had both undergone two consecutive stem cell transplants due to recurrent disease episodes. Both patients presented with premature ovarian failure and returned at ages 29 and 26, respectively, for ovarian cortex transplantation. Hormonal secretions and menstrual function were closely monitored both prior and in the months following the ovarian transplantation. Menstruation resumed at 7 and 5 months post-transplantation, respectively. FSH and LH levels significantly decreased as early as 1 and 3 months before the first menstruation. As for ovarian hormonal secretion, AMH, measured with an ultra-sensitive assay (“pico AMH”), and Inhibin B were the first to increase, starting 1 month before the resumption of menstruation. Subsequently, AMH levels consistently remained very low throughout the follow-up, as did androgens, which showed a slight increase after the graft but remained at postmenopausal levels. Pico AMH, measured by an ultra-sensitive assay, Inhibin B and estradiol are the first ovarian hormones to be secreted following an ovarian graft, with levels rising 1 month prior the return of menstruation. However, the earliest hormonal indicators of graft success are the significant drops in FSH and LH levels, accompanied by a rise in estradiol levels, which occur 1–3 months before menstruation resumes.

Context. Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of the twenty predisposing genes described to date.Purpose. To describe the experience of one endocrine oncogenetic laboratory over a period of 21 years (2001-2022), from the beginning of PPGL genotyping with Sanger sequencing in 2001 to the implementation of next-generation sequencing (NGS).Method. The activity database of an academic oncogenetic laboratory was searched to extract patients/relatives identified with a pathogenic variant/likely pathogenic variant (PV/LPV) over a period of 21 years. Clinical and genetic data were compared.Results. 606 index cases with PPGL and 444 relatives were genotyped. Genotyping of index cases was performed by Sanger sequencing and gene deletion analysis in 327 cases and by NGS in 279. Germline PV/LPV spanning 10 genes was identified in 165 index cases (27.2%). Several recurrent PV/LPVs in SDHx were observed in non-related index cases, the most frequent being SDHD, c.170-1G>T (n=28). This subgroup showed great phenotypic variability both between and within families in terms of both tumor location and number. Four patients (1.1%) with PV/LPV in SDHx had 3PA (Pituitary Adenoma and pheochromocytoma/paraganglioma) syndrome. 258 relatives (58.1%) had inherited a PV/LPV in one driver gene. The rate of PV/LPV carriers who were symptomatic at first imaging evaluation was 32%, but varied between <20% in SDHB and SDHC and >50% in SDHD, VHL and MAX.Conclusion. Our experience confirmed previously established genotype-phenotype correlations, but also highlights atypical clinical presentations, even for the same genetic variant. These data must be taken into account for optimal patient follow-up and management.

RESEARCH QUESTION:Does the aggressiveness of Hodgkin lymphoma impact the oocyte cohort after ovarian stimulation for fertility preservation? DESIGN:A retrospective analysis of prospectively collected data was undertaken. Seventy-seven chemo-naive women with newly diagnosed Hodgkin lymphoma were enrolled prospectively at the Observatory and Fertility Preservation Centre, Lille University Hospital, France between 2012 and 2021. Seventy-eight ovarian stimulation cycles were performed. Oocyte cohort characteristics were compared between patients with early and intermediate stage disease [German Hodgkin Study Group (GHSG) I + II] and patients with advanced stage disease (GHSG III). Among the GHSG III patients, the influence of the Hasenclever score on fertility preservation outcomes was analysed. The primary endpoint was the number of metaphase II oocytes (MII) retrieved. RESULTS:The groups were comparable except for body mass index (BMI). Overall, a median of seven (interquartile range 4-11) MII oocytes were retrieved. Before and after adjustment for BMI, age, pre-treatment anti-Müllerian hormone concentration, and total dose of gonadotrophin, GHSG status did not have a significant impact on the number of MII oocytes retrieved [relative risk 0.96, 95% confidence interval 0.68-1.34; P = 0.79] or the other ovarian stimulation outcomes. The Hasenclever score was not significantly associated with the number of MII oocytes retrieved. CONCLUSION:Tumour aggressiveness was not found to have a significant influence on the number of MII oocytes retrieved in young women with Hodgkin lymphoma. These results suggest that fertility preservation should be proposed systematically, regardless of the stage of Hodgkin disease, in young women.

Other Supporting Colleagues from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Supplementary Table 2 from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out