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1.
Haematologica ; 109(2): 466-478, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37496419

RESUMEN

Chronic lymphocytic leukemia (CLL) is an incurable indolent non-Hodgkin lymphoma characterized by tumor B cells that weakly express a B-cell receptor. The mutational status of the variable region (IGHV) within the immunoglobulin heavy chain (IGH) locus is an important prognosis indicator and raises the question of the CLL cell of origin. Mutated IGHV gene CLL are genetically imprinted by activation-induced cytidine deaminase (AID). AID is also required for IGH rearrangements: class switch recombination and recombination between switch Mu (Sµ) and the 3' regulatory region (3'RR) (Sµ-3'RRrec). The great majority of CLL B cells being unswitched led us to examine IGH rearrangement blockade in CLL. Our results separated CLL into two groups on the basis of Sµ-3'RRrec counts per sample: Sµ-3'RRrecHigh cases (mostly unmutated CLL) and Sµ-3'RRrecLow cases (mostly mutated CLL), but not based on the class switch recombination junction counts. Sµ-3'RRrec appeared to be ongoing in Sµ-3'RRrecHigh CLL cells and comparison of Sµ-3'RRrec junction structural features pointed to different B-cell origins for both groups. In accordance with IGHV mutational status and PIM1 mutation rate, Sµ-3'RRrecHigh CLL harbor a non-germinal center experienced B-cell imprint while Sµ-3'RRrecLow CLL are from AID-experienced B cells from a secondary lymphoid organ. In addition to the proposals already made concerning the CLL cell of origin, our study highlights that analysis of IGH recombinatory activity can identify CLL cases from different origins. Finally, on-going Sµ-3'RRrec in Sµ-3'RRrecHigh cells appeared to presumably be the consequence of high c-MYC expression, as c-MYC overexpression potentiated IGH rearrangements and Sµ-3'RRrec, even in the absence of AID for the latter.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Cadenas Pesadas de Inmunoglobulina/genética , Linfocitos B/patología , Secuencias Reguladoras de Ácidos Nucleicos , Receptores de Antígenos de Linfocitos B/genética
2.
Clin Genet ; 95(1): 177-181, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30298622

RESUMEN

Reunion Island is a French oversea department in the Indian Ocean with 1.6/1000, an estimated prevalence of deafness that is almost double as compared to the mainland France. Twelve children having isolated bilateral prelingual profound deafness along with motor delay attributed to vestibular areflexia were enrolled. Their mean walking age was 19 months. Electroretinography and temporal bone CT-scans were normal in all cases. A novel homozygous frameshift lipoma HMGIC fusion partner-like 5 (LHFPL5) variant c.185delT p.(Phe62Serfs*23) was identified using whole-exome sequencing. It was found in seven families. Four patients from two different families from both Reunion Island and mainland France, were compound heterozygous: c.185delT p.(Phe62Serfs*23) and c.472C > T p.(Arg158Trp). The phenotype observed in our patients completely mimics the hurry-scurry (hscy) murine Tmhs knock-out model. The recurrent occurrence of same LHFPL5 variant in Reunion Island is attributed to common ancestor couple born in 1693.


Asunto(s)
Vestibulopatía Bilateral/genética , Sordera/genética , Proteínas de la Membrana/genética , Trastornos Motores/genética , Animales , Vestibulopatía Bilateral/diagnóstico por imagen , Vestibulopatía Bilateral/fisiopatología , Sordera/diagnóstico por imagen , Sordera/fisiopatología , Electrorretinografía , Femenino , Mutación del Sistema de Lectura/genética , Homocigoto , Humanos , Lactante , Masculino , Ratones , Trastornos Motores/diagnóstico por imagen , Trastornos Motores/fisiopatología , Linaje , Tomografía Computarizada por Rayos X , Secuenciación del Exoma
3.
J Peripher Nerv Syst ; 24(1): 139-144, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30734407

RESUMEN

Neurofilaments are neuron-specific intermediate filaments essential for the radial growth of axons during development and the maintenance of axonal diameter. Pathogenic variants of Neurofilament Light (NEFL) are associated with CMT1F, CMT2E, and CMTDIG and have been observed in less than 1% of Charcot-Marie-Tooth (CMT) cases, resulting in the reporting of 35 variants in 173 CMT patients to date. However, only six variants have been reported in 17 patients with impaired hearing. No genotype-phenotype correlations have yet been established. Here, we report an additional case: a 69-year-old female, who originally presented with axonal sensory and motor neuropathy at the age of 45, associated with moderate sensorineural hearing loss, with a slight slope at high frequencies. Next-generation sequencing identified a novel pathogenic variant: c.269A > G, p.(Glu90Gly). Hearing impairment is often linked to CMT due to pathogenic variants of NEFL, especially p.(Glu90Lys) and p.(Asn98Ser), and in our case p.(Glu90Gly). These pathogenic variants are all located at hot spots, in the head domain and the two ends of the rod domain of the protein.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Pérdida Auditiva Sensorineural/genética , Proteínas de Neurofilamentos/genética , Anciano , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Literatura de Revisión como Asunto
4.
J Peripher Nerv Syst ; 22(2): 77-84, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28448692

RESUMEN

PHARC syndrome (MIM612674) is an autosomal recessive neurodegenerative pathology that leads to demyelinating Polyneuropathy, Hearing loss, cerebellar Ataxia, Retinitis pigmentosa, and early-onset Cataracts (PHARC). These various symptoms can appear at different ages. PHARC syndrome is caused by mutations in ABHD12 (α-ß hydrolase domain 12), of which several have been described. We report here a new complex homozygous mutation c.379_385delAACTACTinsGATTCCTTATATACCATTGTAGTCTTACTGCTTTTGGTGAACACA (p.Asn127Aspfs*23). This mutation was detected in a 36-year-old man, who presented neuropathic symptoms from the age of 15, using a next-generation sequencing panel. This result suggests that the involvement of ABHD12 in polyneuropathies is possibly underestimated. We then performed a comparative study of other patients presenting ABHD12 mutations and searched for genotype-phenotype correlations and functional explanations in this heterogeneous population.


Asunto(s)
Ataxia/genética , Catarata/genética , Análisis Mutacional de ADN , Monoacilglicerol Lipasas/genética , Mutación/genética , Polineuropatías/genética , Retinitis Pigmentosa/genética , Adulto , Animales , Ataxia/fisiopatología , Catarata/fisiopatología , Homocigoto , Humanos , Masculino , Modelos Moleculares , Polineuropatías/fisiopatología , Retinitis Pigmentosa/fisiopatología
5.
Hum Mutat ; 37(12): 1354-1362, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27650058

RESUMEN

Perrault syndrome (PS) is a rare autosomal recessive condition characterized by deafness and gonadic dysgenesis. Recently, mutations in five genes have been identified: C10orf2, CLPP, HARS2, HSD17B4, and LARS2. Probands included are presented with sensorineural deafness associated with gonadic dysgenesis. DNA was sequenced using next-generation sequencing (NGS) with a panel of 35 deafness genes including the five Perrault genes. Exonic variations known as pathogenic mutations or detected with <1% frequency in public databases were extracted and subjected to segregation analysis within each family. Both mutations and low coverage regions were analyzed by Sanger sequencing. Fourteen female index patients were included. The screening in four cases has been extended to four family members presenting with PS phenotype. For four unrelated patients (28.6%), causative mutations were identified: three homozygous mutations in C10orf2, CLPP, and HARS2, and one compound heterozygous mutation in LARS2. Three additional heterozygous mutations in LARS2 and HSD17B4 were found in three independent familial cases. All these missense mutations were verified by Sanger sequencing. Familial segregation analyses confirmed the molecular diagnosis in all cases carrying biallelic mutations. Because of NGS, molecular analysis confirmed the clinical diagnosis of PS in 28.6% of our cohort and four novel mutations were found in four Perrault genes. For the unsolved cases, exome sequencing should be performed to search for a sixth unknown PS gene.


Asunto(s)
Disgenesia Gonadal 46 XX/genética , Pérdida Auditiva Sensorineural/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación Missense , Análisis de Secuencia de ADN/métodos , Adolescente , Aminoacil-ARNt Sintetasas/genética , Niño , Preescolar , ADN Helicasas/genética , Endopeptidasa Clp/genética , Exoma , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Proteínas Mitocondriales/genética , Linaje , Proteína-2 Multifuncional Peroxisomal/genética
6.
Surg Innov ; 19(1): 60-6, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21737466

RESUMEN

BACKGROUND: Transoral robotic surgery (TORS) is a recent endoscopic technique to resect selected head and neck cancers. STUDY DESIGN: In total, 13 patients underwent TORS procedure for resection of head and neck cancers of various localizations, within the ENT Department of Limoges University Hospital Center between March and October 2010. RESULTS: Tumor localizations were aryepiglottic fold (n = 3), pyriform sinus (n = 2), posterior pharyngeal wall (n = 2), base of tongue (n = 2), lateral pharyngeal wall (n = 2), vallecula (n = 1), and epiglottis (n = 1). Average TORS setup time was 23 minutes. Average TORS operative time was 45 minutes. Average hospital stay was 8.4 days. CONCLUSIONS: TORS is a new technique that permits excellent resection of selected head and neck cancers with poor morbidity. Future reports on long-term oncologic and functional outcomes are needed to assess the risks and benefits of this approach compared with external approaches and nonsurgical alternatives.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Robótica/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Otorrinolaringológicos/instrumentación , Robótica/instrumentación , Resultado del Tratamiento
7.
Oral Oncol ; 117: 105302, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33905915

RESUMEN

OBJECTIVE: To investigate whether palatine tonsillectomy in youth influences the risk of oropharyngeal cancers (OPC) by assessing the association between history of tonsillectomy and risk of tonsillar, base of tongue (BOT) cancer, and other head and neck cancers (HNC). MATERIALS AND METHODS: RACKAM was a case-case study comparing frequency of tonsillectomy history in individuals diagnosed with HNC from 2013 to 2018 in 15 centers across France. History of tonsillectomy was defined using combined assessment of patients' recollections and surgeons' visualizations of tonsil area. OPC subsite-specific odds ratios (OR) of tonsillectomy were calculated using multinomial logistic regression with non-oropharyngeal HNC as reference. RESULTS: 1045 patients were included in the study. Frequency of tonsillectomy was 19.5% in patients with tonsillar cancer (N = 85), 49.3% in BOT (N = 76), 33.8% in other oropharyngeal cancers (N = 202) and 38.0% in non-oropharyngeal HNC (N = 682). History of tonsillectomy was inversely associated with tonsillar cancer (adjusted OR 0.4; 95% CI 0.2-0.8), and positively associated with BOT cancer (adjusted OR 1.8; 95% CI 1.1-3.1), but was not associated with all OPC combined (adjusted OR 1.1; 95% CI 0.8-1.4). Sensitivity analyses considering only patients' or surgeons' assessments of tonsillectomy provided comparable results. CONCLUSION: We confirm the long-term protective effect of tonsillectomy performed in youth on future risk of tonsillar cancer, and our study is the second to report a concurrent increased risk of BOT cancer. Our data suggest that tonsillectomy in youth shifts the site of the first diagnosed oropharyngeal tumor and has a limited impact on overall risk of OPC.


Asunto(s)
Neoplasias Orofaríngeas , Tonsilectomía , Adolescente , Humanos , Neoplasias Orofaríngeas/epidemiología , Neoplasias Orofaríngeas/cirugía , Tonsila Palatina/cirugía , Tonsilectomía/efectos adversos
8.
Mol Genet Genomic Med ; 7(9): e875, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31338985

RESUMEN

BACKGROUND: CMTX5 is characterized by peripheral neuropathy, early-onset sensorineural hearing impairment, and optic neuropathy. Only seven variants have been reported and no genotype-phenotype correlations have yet been established. PRPS1 has a crystallographic structure, as it is composed of three dimers that constitute a hexamer. METHODS: Next-generation sequencing (NGS) was performed using a custom 92-gene panel designed for the diagnosis of Charcot-Marie-Tooth (CMT) and associated neuropathies. RESULTS: We report the case of a 35-year-old male, who had presented CMT and hearing loss since childhood associated to bilateral optic neuropathy without any sign of retinitis pigmentosa. A new hemizygous variant on chromosomic position X:106,882,604, in the PRPS1 gene, c.202A > T, p.(Met68Leu) was found. This change is predicted to lead to an altered affinity between the different subunits in the dimer, thereby may prevent the hexamer formation. CONCLUSION: CMTX5 is probably under-diagnosed, as an overlap among the different features due to PRPS1 exists. Patients who developed polyneuropathy associated to sensorineural deafness and optic atrophy during childhood should be assessed for PRPS1.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Dimerización , Pérdida Auditiva Central/genética , Pérdida Auditiva Sensorineural/genética , Trastornos Musculares Atróficos/genética , Atrofias Ópticas Hereditarias/genética , Polineuropatías/genética , Ribosa-Fosfato Pirofosfoquinasa/genética , Adulto , Enfermedad de Charcot-Marie-Tooth/diagnóstico , Sordera/genética , Estudios de Asociación Genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Genotipo , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Masculino , Modelos Moleculares , Linaje , Fenotipo , Polineuropatías/diagnóstico , Conformación Proteica , Retinitis Pigmentosa , Ribosa-Fosfato Pirofosfoquinasa/química
9.
Mol Genet Genomic Med ; 7(9): e839, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31393079

RESUMEN

BACKGROUND: The most common inherited peripheral neuropathy is Charcot-Marie-Tooth disease (CMT), with a prevalence of 1/2500. Other symptoms can be associated to the condition, such as hearing loss. Currently, no global hearing impairment assessment has been determined, and the physiopathology is not well known. METHODS: The aim of the study was to analyze among a French series of 3,412 patients with inherited peripheral neuropathy (IPN), the ones who also suffer from hearing loss, to establish phenotype-genotype correlations. An NGS strategy for IPN one side and nonsyndromic hearing loss (NSHL) on the other side, were performed. RESULTS: Hearing loss (HL) was present in only 44 patients (1.30%). The clinical data of 27 patients were usable. Demyelinating neuropathy was diagnosed in 15 cases and axonal neuropathy in 12 cases. HL varied from mild to profound. Five cases of auditory neuropathy were noticed. Diagnosis was made for 60% of these patients. Seven novel pathogenic variants were discovered in five different genes: PRPS1; MPZ; SH3TC2; NEFL; and ABHD12. Two patients with PMP22 variant, had also an additional variant in COCH and MYH14 respectively. No pathogenic variant was found at the DFNB1 locus. Genotype-phenotype correlations do exist, especially with SH3TC2, PRPS1, ABHD12, NEFL, and TRPV4. CONCLUSION: Involvement of PMP22 is not enough to explain hearing loss in patients suffering from IPN. HL can be due to cochlear impairment and/or auditory nerve dysfunction. HL is certainly underdiagnosed, and should be evaluated in every patient suffering from IPN.


Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/genética , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Alelos , Biología Computacional , Femenino , Francia/epidemiología , Estudios de Asociación Genética/métodos , Pruebas Genéticas , Genotipo , Pérdida Auditiva/epidemiología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Patrón de Herencia , Masculino , Persona de Mediana Edad , Mutación , Linaje , Enfermedades del Sistema Nervioso Periférico/epidemiología , Fenotipo
10.
Bull Cancer ; 104(10): 850-857, 2017 Oct.
Artículo en Francés | MEDLINE | ID: mdl-29031506

RESUMEN

INTRODUCTION: The aim of this study was to correlate the cytological and histological results and evaluate the diagnostic performance of fine-needle aspiration cytology (FNAC) in the management of parotid gland tumors. METHODS: This retrospective study included 160 patients with a parotid gland tumor who underwent fine-needle aspiration and parotidectomy surgery between January 2005 and August 2016 at the Limoges university hospital center. RESULTS: On 160 fine-needle aspirations performed, fine-needle aspiration diagnoses were: 77 benign lesions, 35 malignant lesions and 48 non-diagnostic cases. Final histological diagnosis revealed there were 113 benign lesions and 47 malignant lesions. A hundred and one cytological diagnoses were accurate over 112 contributive fine-needle aspirations: seven false-negative cases and 4 false-positive cases were observed. The sensitivity, specificity, and accuracy were 82, 95 and 90% respectively for fine-needle aspiration, and 83, 95 and 92% respectively for association of fine-needle aspiration and magnetic resonance imaging. Diagnostic concordance between fine-needle aspiration and final histology for malignant lesions was 78%. A greater number of contributive fine-needle aspirations was observed among experimented operators. DISCUSSION: Fine-needle aspiration is a reliable, safe and effective diagnostic tool that allows good differentiation between malignant and benign diagnosis in the preoperative management of parotid gland tumors. The association of fine-needle aspiration and magnetic resonance imaging (MRI) can improve diagnostic performance.


Asunto(s)
Glándula Parótida/patología , Glándula Parótida/cirugía , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/cirugía , Biopsia con Aguja Fina/métodos , Biopsia con Aguja Fina/estadística & datos numéricos , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Enfermedades de las Parótidas/diagnóstico por imagen , Enfermedades de las Parótidas/patología , Glándula Parótida/diagnóstico por imagen , Neoplasias de la Parótida/diagnóstico por imagen , Estudios Retrospectivos , Sensibilidad y Especificidad
11.
World Neurosurg ; 106: 266-276, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28698084

RESUMEN

INTRODUCTION: Surgery of the craniocervical junction (CCJ) and clivus is technically demanding. For many years, we have used the submandibular retropharyngeal approach for surgery of the upper cervical spine, especially hangman fracture. We hypothesized that submandibular gland resection could offer a significant cranial enlargement of the operative field, up to the clivus. Our aim in this work was to assess the feasibility of an endoscope-assisted retropharyngeal approach to the CCJ and clivus. METHODS: Eight anatomic specimens were used, including 4 silicon-injected specimens. We performed a submandibular retropharyngeal approach with gland resection, and then we exposed the CCJ and clivus. We drilled the C2 vertebral body, odontoid process, C1 anterior arch, and the clivus. We noted 8 anatomic landmarks that were easily identified on each anatomic specimen. These measurements were designed to quantify the exposure of the clivus and CCJ after bone resection. RESULTS: A submandibular approach was feasible in all specimens. The main dimensions of the area of dural exposure after bone drilling were as follows: mean width between C1 lateral masses, 19 mm (range, 17-20 mm); at the tip of the clival window, 18 mm (range, 16-20 mm); distance between the C3 vertebra and the tip of the window within the clivus, 57 mm (range, 55-60 mm). CONCLUSIONS: An endoscopic submandibular retropharyngeal approach provides a simple and straightforward access to the CCJ. It also conveniently exposes the clivus. This technique could be added to the techniques used for this difficult surgery.


Asunto(s)
Vértebras Cervicales/cirugía , Fosa Craneal Posterior/cirugía , Neuroendoscopía/métodos , Glándula Submandibular/cirugía , Cadáver , Femenino , Humanos , Masculino , Modelos Anatómicos
12.
Auris Nasus Larynx ; 43(1): 105-7, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26142980

RESUMEN

A 61-year-old man with obstructive sleep apnea syndrome and normal BMI complained of dyspnea. Nasofibroscopy revealed a global and major oedema of the glottis and supraglottis and also a paralysis of the left vocal fold. CT-scan pointed out a spontaneous hyperdensity of the left arytenoid cartilage. A tracheostomy was performed. Clinical examination revealed large hands and macroglossy with high IGF1 rate. MRI confirmed a supracentimetric pituitary adenoma. To our knowledge, this is the first description of a case of acute respiratory distress due to unilateral larynx paralysis leading to acromegaly diagnosis. This is due to submucosal hypertrophy and vocal cord immobility.


Asunto(s)
Acromegalia/diagnóstico , Adenoma/diagnóstico , Obstrucción de las Vías Aéreas/etiología , Disnea/etiología , Edema/diagnóstico , Adenoma Hipofisario Secretor de Hormona del Crecimiento/diagnóstico , Laringoestenosis/diagnóstico , Parálisis de los Pliegues Vocales/diagnóstico , Acromegalia/complicaciones , Adenoma/complicaciones , Obstrucción de las Vías Aéreas/cirugía , Cartílago Aritenoides/diagnóstico por imagen , Edema/complicaciones , Adenoma Hipofisario Secretor de Hormona del Crecimiento/complicaciones , Humanos , Laringoscopía , Laringoestenosis/complicaciones , Laringoestenosis/cirugía , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Traqueostomía , Parálisis de los Pliegues Vocales/complicaciones , Parálisis de los Pliegues Vocales/cirugía
13.
Crit Care Res Pract ; 2012: 252719, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-21808730

RESUMEN

Total thyroidectomy involving the adjacent structures of the trachea can cause tracheal damage such as early tracheal necrosis. The authors describe the first case of anterior tracheal necrosis following total thyroidectomy treated using vacuum-assisted closure device. After two weeks of VAC therapy, there was no evidence of ongoing infection and the trachea was partially closed around a tracheotomy cannula, removed after 3 months. The use of a VAC therapy to reduce and close the tracheal rent and to create a rapid granulation tissue over tracheal structure appeared as a good opportunity after anterior tracheal necrosis.

14.
Skull Base Rep ; 1(2): 133-8, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23984216

RESUMEN

Carotid pseudoaneurysms of petrous localization are rare. They are mostly due to trauma, tumoral or infectious diseases, or a result of iatrogenic complications after skull base surgery. Symptoms such as facial paralysis are exceptional and have rarely been described in the literature until now. We report the case of a 64-year-old woman, who developed left peripheral facial paralysis induced by two carotid pseudoaneurysms in their intrapetrous section. The treatment is endovascular, despite the high morbidity rate. She was first put on antiplatelet medications, before the left carotid aneurysm was bypassed thanks to a self-expanding pipeline-type stent with flow diversion. The left peripheral facial paralysis was due to the compression exerted by the left carotid aneurysm, probably a congenital malformation. The progressive palsy recovery was fist due to the aneurysmal thrombosis, then to the secondary fibrosis.

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