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1.
Am J Hum Genet ; 108(1): 8-15, 2021 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-33417889

RESUMEN

The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as "GENE-related phenotype descriptor" (e.g., "CFTR-related cystic fibrosis"). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.


Asunto(s)
Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Genómica/métodos , Fibrosis Quística/diagnóstico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Genotipo , Humanos , Mutación/genética , Fenotipo
2.
Genet Med ; 23(7): 1315-1324, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33864021

RESUMEN

PURPOSE: Several clinical phenotypes including fetal hydrops, central conducting lymphatic anomaly or capillary malformations with arteriovenous malformations 2 (CM-AVM2) have been associated with EPHB4 (Ephrin type B receptor 4) variants, demanding new approaches for deciphering pathogenesis of novel variants of uncertain significance (VUS) identified in EPHB4, and for the identification of differentiated disease mechanisms at the molecular level. METHODS: Ten index cases with various phenotypes, either fetal hydrops, CM-AVM2, or peripheral lower limb lymphedema, whose distinct clinical phenotypes are described in detail in this study, presented with a variant in EPHB4. In vitro functional studies were performed to confirm pathogenicity. RESULTS: Pathogenicity was demonstrated for six of the seven novel EPHB4 VUS investigated. A heterogeneity of molecular disease mechanisms was identified, from loss of protein production or aberrant subcellular localization to total reduction of the phosphorylation capability of the receptor. There was some phenotype-genotype correlation; however, previously unreported intrafamilial overlapping phenotypes such as lymphatic-related fetal hydrops (LRFH) and CM-AVM2 in the same family were observed. CONCLUSION: This study highlights the usefulness of protein expression and subcellular localization studies to predict EPHB4 variant pathogenesis. Our accurate clinical phenotyping expands our interpretation of the Janus-faced spectrum of EPHB4-related disorders, introducing the discovery of cases with overlapping phenotypes.


Asunto(s)
Hidropesía Fetal , Receptor EphB4 , Estudios de Asociación Genética , Humanos , Fenotipo , Fosforilación , Receptor EphB4/genética
3.
Am J Hum Genet ; 98(5): 909-918, 2016 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-27132593

RESUMEN

The proteins encoded by TELO2, TTI1, and TTI2 interact to form the TTT complex, a co-chaperone for maturation of the phosphatidylinositol 3-kinase-related protein kinases (PIKKs). Here we report six affected individuals from four families with intellectual disability (ID) and neurological and other congenital abnormalities associated with compound heterozygous variants in TELO2. Although their fibroblasts showed reduced steady-state levels of TELO2 and the other components of the TTT complex, PIKK functions were normal in cellular assays. Our results suggest that these TELO2 missense variants result in loss of function, perturb TTT complex stability, and cause an autosomal-recessive syndromic form of ID.


Asunto(s)
Discapacidad Intelectual/etiología , Chaperonas Moleculares/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas de Unión a Telómeros/genética , Adolescente , Proteínas Portadoras/genética , Niño , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Linaje , Fosfatidilinositol 3-Quinasas/genética
5.
Am J Med Genet A ; 179(8): 1543-1546, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31207089

RESUMEN

1p36 deletion syndrome is a well-described condition with a recognizable phenotype, including cognitive impairment, seizures, and structural brain anomalies such as periventricular leukomalacia (PVL). In a large series of these individuals by Battaglia et al., "birth history was notable in 50% of the cases for varying degrees of perinatal distress." Given the potential for perinatal distress, seizures and PVL, we questioned if this disorder has clinical overlap with hypoxic ischemic encephalopathy (HIE). We reviewed the medical records of 69 individuals with 1p36 deletion to clarify the perinatal phenotype of this disorder and determine if there is evidence of perinatal distress and/or hypoxic injury. Our data provides evidence that these babies have signs of perinatal distress. The majority (59% term; 75% preterm) needed resuscitation and approximately 18% had cardiac arrest. Most had abnormal brain imaging (84% term; 73% preterm) with abnormal white matter findings in over half of patients. PVL or suggestion of "hypoxic insult" was present in 18% of term and 45% of preterm patients. In conclusion, individuals with 1p36 deletion have evidence of perinatal distress, white matter changes, and seizures, which can mimic HIE but are likely related to their underlying chromosome disorder.


Asunto(s)
Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/genética , Hipoxia-Isquemia Encefálica/diagnóstico , Fenotipo , Distrés Psicológico , Deleción Cromosómica , Cromosomas Humanos Par 1/genética , Diagnóstico Diferencial , Femenino , Humanos , Recién Nacido , Masculino , Embarazo
6.
Genet Med ; 20(9): 965-975, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29300384

RESUMEN

PURPOSE: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS. METHODS: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. RESULTS: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. CONCLUSION: Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.


Asunto(s)
Enfermedad de Hirschsprung/diagnóstico , Enfermedad de Hirschsprung/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Microcefalia/diagnóstico , Microcefalia/genética , Anomalías Múltiples/genética , Adolescente , Adulto , Niño , Preescolar , Facies , Femenino , Estudios de Asociación Genética/métodos , Genotipo , Humanos , Lactante , Masculino , Mutación , Fenotipo , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/genética
7.
J Hum Genet ; 63(12): 1231-1239, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30232357

RESUMEN

We present a case of a newborn female with multiple anomalies demonstrating that the causes of imprinting disorders rely not only on the parent-of-origin of the chromosomal aberrations, but also the scope of genes contained in the imprinted region. The newborn female presented with prenatal polyhydramnios, neonatal respiratory distress, distal contractures, abdominal hernia, bell-shaped thorax, and abnormal ribs. The neonate required mechanical ventilation due to apnea, underwent surgery for laryngomalacia, and showed development delay by age 11 months. Chromosomal microarray analysis identified a single copy number loss in chromosome region 14q32.2q32.31, containing genes that are differentially expressed based on parent-of-origin. Microarray analysis also confirmed the identical deletion in the patient's mother, who was reported to be normal. Additional molecular analyses determined the exact size and breakpoints of the deletion as well as methylation states in both the patient and her mother. The maternally transmitted deletion was responsible for Kagami-Ogata syndrome in the patient.


Asunto(s)
Anomalías Múltiples/genética , Secuencia de Bases , Cromosomas Humanos Par 14/genética , Eliminación de Secuencia , Anomalías Múltiples/patología , Femenino , Humanos , Síndrome
9.
Genet Med ; 19(6): 691-700, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27831545

RESUMEN

PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations. RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.


Asunto(s)
Encéfalo/diagnóstico por imagen , Enfermedad de Hirschsprung/diagnóstico por imagen , Discapacidad Intelectual/diagnóstico por imagen , Imagen por Resonancia Magnética , Microcefalia/diagnóstico por imagen , Neuroimagen , Encéfalo/patología , Niño , Preescolar , Estudios de Cohortes , Epilepsia/patología , Facies , Femenino , Genotipo , Haploinsuficiencia , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/patología , Humanos , Lactante , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Estudios Longitudinales , Masculino , Microcefalia/genética , Microcefalia/patología , Fenotipo , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/genética
10.
Am J Med Genet A ; 173(7): 1848-1857, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28464518

RESUMEN

Congenital heart defects (CHD) are the most frequent type of congenital anomaly and are often associated with genetic and chromosomal syndromes. Haploinsufficiency of TAB2 (TGF-beta activated kinase 1/MAP3K7 binding protein 2) has been proposed to cause valvular and cardiac outflow tract structural abnormalities. In this study, we describe 13 newly identified individuals with microdeletions of chromosome 6q25.1 that involve TAB2. One of the patients in our study cohort has the smallest deletion yet reported, affecting only TAB2. These were compared to 27 other patients reported in the published literature or DECIPHER to have similar microdeletions, for a total study group of 40 patients. Our study shows that individuals with TAB2 deletions are predisposed to developing a primary cardiomyopathy with reduced systolic function, even in the absence of CHD. Our study cohort also shares a number of non-cardiac phenotypic findings: characteristic dysmorphic facial features, intrauterine growth restriction and/or postnatal proportionate short stature, hypotonia, developmental delay and/or intellectual disability, and connective tissue abnormalities. We conclude that a microdeletion of 6q25.1 that includes TAB2 causes a distinctive, multi-systemic syndrome. The 6q25.1 microdeletion syndrome should be considered in a patient with cardiomyopathy or a CHD, especially valve and/or atrial or ventricular septal abnormalities, and with phenotypic features described in this study. We recommend that patients with a TAB2 deletion be screened longitudinally for systolic heart failure, even if an initial echocardiogram is normal.

12.
Am J Med Genet A ; 161A(4): 717-31, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23495017

RESUMEN

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray-based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P = 6.08 × 10(-7) ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1.


Asunto(s)
Moléculas de Adhesión Celular Neuronal/genética , Eliminación de Gen , Proteínas del Tejido Nervioso/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Adolescente , Adulto , Trastorno Autístico/genética , Proteínas de Unión al Calcio , Niño , Preescolar , Hibridación Genómica Comparativa , Discapacidades del Desarrollo/genética , Exones , Facies , Femenino , Interacción Gen-Ambiente , Estudio de Asociación del Genoma Completo , Humanos , Lactante , Discapacidad Intelectual/genética , Masculino , Persona de Mediana Edad , Moléculas de Adhesión de Célula Nerviosa , Penetrancia , Fenotipo , Esquizofrenia/genética , Adulto Joven
13.
Eur J Hum Genet ; 29(9): 1384-1395, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33594261

RESUMEN

Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K+ channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann-Laband and Temple-Baraitser syndromes, caused by dominant variants in KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K+ conductance, referred to as syndromic neurodevelopmental K+ channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3.


Asunto(s)
Anomalías Múltiples/genética , Canalopatías/genética , Anomalías Craneofaciales/genética , Canales de Potasio Éter-A-Go-Go/genética , Fibromatosis Gingival/genética , Mutación con Ganancia de Función , Hallux/anomalías , Deformidades Congénitas de la Mano/genética , Discapacidad Intelectual/genética , Uñas Malformadas/genética , Canales de Potasio/genética , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/genética , Pulgar/anomalías , Anomalías Múltiples/patología , Adolescente , Adulto , Canalopatías/patología , Niño , Anomalías Craneofaciales/patología , Femenino , Fibromatosis Gingival/patología , Hallux/patología , Deformidades Congénitas de la Mano/patología , Humanos , Discapacidad Intelectual/patología , Masculino , Uñas Malformadas/patología , Fenotipo , Pulgar/patología
14.
Clin Lab Med ; 40(1): 61-67, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32008640

RESUMEN

Direct-to-consumer genetic testing came on the scene 2 decades ago as a means for allowing consumers to access their genetic information without the involvement of a physician or genetic counselor. Results are delivered directly to the consumer, often leading to misinterpretation and needless medical interventions or false reassurance. Increasingly, we are seeing these patients in our genetics clinics for test interpretation, management guidance and confirmatory genetic testing.


Asunto(s)
Pruebas Dirigidas al Consumidor , Pruebas Genéticas , Asesoramiento Genético , Estudio de Asociación del Genoma Completo , Humanos , Médicos , Polimorfismo de Nucleótido Simple/genética
15.
Am J Med Genet C Semin Med Genet ; 151C(3): 241-54, 2009 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-19621460

RESUMEN

In 2006, all clinical genetics practices in Northern New England (Vermont, New Hampshire, and Maine) formed a learning collaborative with the purpose of improving genetic health care and outcomes. This article describes the current status of this effort. The methodology is based on our own modifications of the Institute of Healthcare Improvement "Breakthrough Series" and the Northern New England Cystic Fibrosis Consortium. Because of similarities across practices and the availability of existing published practice parameters, the clinical genetics evaluation of the child with developmental delay or intellectual disability was chosen as the topic to be studied. The aim was to improve the rate of etiological diagnosis of those with developmental delays referred to each genetics center by improving the processes of care. Process and outcomes were evaluated. Four of five sites also evaluated the impact of array comparative genomic hybridization (a-CGH) laboratory testing of such patients. There was significant site-to-site variation in the rate of new diagnoses by a-CGH with the average new diagnosis rate of 11.8% (range 5.4-28.8%). Barriers to implementation of the process and outcome data collection and analysis were significant and related to time pressures, lack of personnel or staff to support this activity, and competing quality improvement initiatives at the institutional home of some genetics centers.


Asunto(s)
Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Servicios Genéticos/organización & administración , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Niño , Atención a la Salud , Femenino , Pruebas Genéticas/métodos , Humanos , Cariotipificación , Masculino , New England , Hibridación de Ácido Nucleico , Evaluación de Resultado en la Atención de Salud , Proyectos Piloto , Garantía de la Calidad de Atención de Salud , Indicadores de Calidad de la Atención de Salud
16.
Sci Rep ; 7: 39636, 2017 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-28051109

RESUMEN

We retrospectively analyzed electronic medical records of patients with Ehlers-Danlos Syndrome hypermobility type (HEDS), including demographic information, workup, rheumatological diagnoses in order to determine its association with rheumatological conditions. HEDS Patients were stratified according to level of workup received (no additional work (physical exam only) = NWU, limited workup = LWU, comprehensive workup = CWU)). HEDS patients were predominantly female (21:4, F:M). The percentage of patients with at least one rheumatological condition was significantly correlated with level of workup (NWU, 9.2%; LWU, 33.3%, CWU, 67.1%; p-value < 0.0001). The HLA-B27 antigen was more prevalent (p-value < 2.2 × 10-8) in the CWU HEDS patients (23.9%) than in the general population of the United States (6.1%). HEDS with CWU were associated with more rheumatological conditions (i.e. psoriasis, ankylosing spondylitis, rheumatoid arthritis, fibromyalgia) than those with NWU or LWU. In conclusion, HEDS is associated with complicated rheumatological conditions, which are uncovered by comprehensive workup. These conditions require different clinical management strategies than HEDS, and left untreated could contribute to the pain or even physical disability (i.e. joint erosions) in HEDS patients. While the mechanisms underlying these associations are unknown, it is important that all HEDS patients receive adequate workup to ensure a complete clinical understanding for the best care strategy possible.


Asunto(s)
Síndrome de Ehlers-Danlos/epidemiología , Enfermedades Reumáticas/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Síndrome de Ehlers-Danlos/complicaciones , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Reumáticas/complicaciones , Adulto Joven
18.
Eur J Hum Genet ; 23(12): 1615-26, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25853300

RESUMEN

Array comparative genomic hybridization (aCGH) is a powerful genetic tool that has enabled the identification of novel imbalances in individuals with intellectual disability (ID), autistic disorders and congenital malformations. Here we report a 'genotype first' approach using aCGH on 13 unrelated patients with 19p13.3 submicroscopic rearrangement (11 deletions and 2 duplications) and review cases in the literature and in public databases. Shared phenotypic features suggest that these patients represent an interstitial microdeletion/microduplication syndrome at 19p13.3. Common features consist of abnormal head circumference in most patients (macrocephaly with the deletions and microcephaly with the duplications), ID with developmental delay (DD), hypotonia, speech delay and common dysmorphic features. The phenotype is associated with at least a ~0.113 Mb critical region harboring three strong candidate genes probably associated with DD, ID, speech delay and other dysmorphic features: MAP2K2, ZBTB7A and PIAS4, an E3 ubiquitin ligase involved in the ubiquitin signaling pathways, which we hypothesize for the first time to be associated with head size in humans.


Asunto(s)
Deleción Cromosómica , Duplicación Cromosómica , Cromosomas Humanos Par 19/genética , Discapacidades del Desarrollo/genética , Megalencefalia/genética , Microcefalia/genética , Proteínas Inhibidoras de STAT Activados/genética , Niño , Preescolar , Proteínas de Unión al ADN/genética , Discapacidades del Desarrollo/patología , Femenino , Humanos , Lactante , MAP Quinasa Quinasa 2/genética , Masculino , Megalencefalia/patología , Microcefalia/patología , Proteínas de Unión a Poli-ADP-Ribosa , Síndrome , Factores de Transcripción/genética
20.
Mol Genet Metab ; 88(3): 272-9, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16459121

RESUMEN

Mutations in the DAX1 (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita (AHC) critical region on the X chromosome gene 1; NR0B1) cause X-linked AHC, a disease characterized by primary adrenal failure in infancy and hypogonadotropic hypogonadism. All known missense mutations impair DAX1 repression of steroidogenic factor 1 (SF1) transactivation and have been localized to the putative ligand binding domain. Here, an asymptomatic father and his late-onset AHC daughter were both shown to share a novel DAX1 mutation (C200W), the first missense mutation identified in the hinge region of DAX1. Using immunohistochemistry we demonstrate that the sub-cellular localization of the C200W mutant DAX1 protein is shifted from the nucleus to the cytoplasm. The disturbed localization of the C200W mutant in transfected cells correlates with impaired transcriptional repression activity. The import defect is relatively mild, retaining 80% of wild-type activity, which may explain the unusually mild phenotype. Import of DAX1 into the nucleus involves a direct interaction with SF1. In vitro assays demonstrate that the C200W mutant retains the ability to functionally interact with SF1, which suggests that SF1-independent interactions of DAX1 could be responsible for the import defect.


Asunto(s)
Hiperplasia Suprarrenal Congénita/genética , Proteínas de Unión al ADN/fisiología , Receptores de Ácido Retinoico/fisiología , Proteínas Represoras/fisiología , Transporte Activo de Núcleo Celular , Adulto , Edad de Inicio , Animales , Núcleo Celular/metabolismo , Células Cultivadas , Niño , Receptor Nuclear Huérfano DAX-1 , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Femenino , Humanos , Masculino , Ratones , Mutación Missense/genética , Linaje , Unión Proteica , Transporte de Proteínas , Pubertad , Factores de Empalme de ARN , Receptores de Ácido Retinoico/genética , Proteínas Represoras/genética , Factor Esteroidogénico 1 , Factores de Transcripción/metabolismo , Activación Transcripcional
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