Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Am J Med Genet A ; 179(9): 1884-1894, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313512

RESUMO

Brachyolmia is a skeletal dysplasia characterized by short spine-short stature, platyspondyly, and minor long bone abnormalities. We describe 18 patients, from different ethnic backgrounds and ages ranging from infancy to 19 years, with the autosomal recessive form, associated with PAPSS2. The main clinical features include disproportionate short stature with short spine associated with variable symptoms of pain, stiffness, and spinal deformity. Eight patients presented prenatally with short femora, whereas later in childhood their short-spine phenotype emerged. We observed the same pattern of changing skeletal proportion in other patients. The radiological findings included platyspondyly, irregular end plates of the elongated vertebral bodies, narrow disc spaces and short over-faced pedicles. In the limbs, there was mild shortening of femoral necks and tibiae in some patients, whereas others had minor epiphyseal or metaphyseal changes. In all patients, exome and Sanger sequencing identified homozygous or compound heterozygous PAPSS2 variants, including c.809G>A, common to white European patients. Bi-parental inheritance was established where possible. Low serum DHEAS, but not overt androgen excess was identified. Our study indicates that autosomal recessive brachyolmia occurs across continents and may be under-recognized in infancy. This condition should be considered in the differential diagnosis of short femora presenting in the second trimester.

2.
Am J Med Genet A ; 179(3): 344-349, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30637921

RESUMO

Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype-up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50-90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrome.

3.
Clin Genet ; 95(4): 496-506, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30666632

RESUMO

Whole-exome sequencing has established IQSEC2 as a neurodevelopmental disability gene. The IQSEC2 variant phenotype includes developmental delay, intellectual disability, epilepsy, hypotonia, autism, developmental regression, microcephaly and stereotypies but is yet to be fully described. Presented here are 14 new patients with IQSEC2 variants. In addition to the established features, we observed: gait ataxia in 7 of 9 (77.8%), drooling in 9 of 14 (64.2%), early feeding difficulties in 7 of 14 (50%), structural brain abnormalities in 6 of 13 (46.2%), brachycephaly in 5 of 14 (35.7%), and scoliosis and paroxysms of laughter each in 4 of 14 (28.6%). We suggest that these are features of the IQSEC2-related disorder. Gastrostomy requirement, plagiocephaly, strabismus and cortical blindness, each seen in 2 of 14 (14.3%), may also be associated. Shared facial features were noted in 8 of 14 patients, and shared hair patterning was identified in 5 of 14 patients. This study further delineates the IQSEC2 phenotypic spectrum and supports the notion of an emerging IQSEC2 syndrome. We draw parallels between the IQSEC2-related disorder and the Angelman-/Rett-/Pitt-Hopkins syndrome group of conditions and recommend the addition of IQSEC2 to epilepsy and developmental delay gene panels. We observed discordant phenotypes in monozygotic twins and apparent gonadal mosaicism, which has implications for recurrence risk counselling in the IQSEC2-related disorder.

4.
Am J Med Genet A ; 176(9): 1950-1955, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30144375

RESUMO

Transient receptor potential vanilloid 6 (TRPV6) functions in tetramer form for calcium transport. Until now, TRPV6 has not been linked with skeletal development disorders. An infant with antenatal onset thoracic insufficiency required significant ventilatory support. Skeletal survey showed generalized marked undermineralization, hypoplastic fractured ribs, metaphyseal fractures, and extensive periosteal reaction along femoral, tibial, and humeral diaphyses. Parathyroid hormone (PTH) elevation (53.4-101 pmol/L) initially suggested PTH signaling disorders. Progressively, biochemical normalization with radiological mineralization suggested recovery from in utero pathophysiology. Genomic testing was undertaken and in silico protein modeling of variants. No abnormalities in antenatal CGH array or UPD14 testing. Postnatal molecular genetic analysis found no causative variants in CASR, GNA11, APS21, or a 336 gene skeletal dysplasia panel investigated by whole exome sequencing. Trio exome analysis identified compound heterozygous TRPV6 likely pathogenic variants: novel maternally inherited missense variant, c.1978G > C p.(Gly660Arg), and paternally inherited nonsense variant, c.1528C > T p.(Arg510Ter), confirming recessive inheritance. p.(Gly660Arg) generates a large side chain protruding from the C-terminal hook into the interface with the adjacent TRPV6 subunit. In silico protein modeling suggests steric clashes between interface residues, decreased C-terminal hook, and TRPV6 tetramer stability. The p.(Gly660Arg) variant is predicted to result in profound loss of TRPV6 activity. This first case of a novel dysplasia features severe but improving perinatal abnormalities. The TRPV6 compound heterozygous variants appear likely to interfere with fetoplacental calcium transfer crucial for in utero skeletal development. Astute clinical interpretation of evolving perinatal abnormalities remains valuable in complex calcium and bone pathophysiology and informs exome sequencing interpretation.

5.
Hum Mutat ; 39(10): 1360-1365, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30040876

RESUMO

Saethre-Chotzen syndrome (SCS), one of the most common forms of syndromic craniosynostosis (premature fusion of the cranial sutures), results from haploinsufficiency of TWIST1, caused by deletions of the entire gene or loss-of-function variants within the coding region. To determine whether non-coding variants also contribute to SCS, we screened 14 genetically undiagnosed SCS patients using targeted capture sequencing, and identified novel single nucleotide variants (SNVs) in the 5' untranslated region (UTR) of TWIST1 in two unrelated SCS cases. We show experimentally that these variants, which create translation start sites in the TWIST1 leader sequence, reduce translation from the main open reading frame (mORF). This is the first demonstration that non-coding SNVs of TWIST1 can cause SCS, and highlights the importance of screening the 5' UTR in clinically diagnosed SCS patients without a coding mutation. Similar 5' UTR variants, particularly of haploinsufficient genes, may represent an under-ascertained cause of monogenic disease.

6.
Hum Mutat ; 39(9): 1226-1237, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29897170

RESUMO

Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip, and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall-Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only.

7.
Pediatr Dermatol ; 35(4): e221-e223, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29683223

RESUMO

Mid-dermal elastolysis is an acquired skin condition affecting the elastin fibers of the dermis, resulting in laxity of the skin. We report a case of mid-dermal elastolysis for which novel treatment with mycophenolate mofetil was successful.


Assuntos
Tecido Elástico/patologia , Inibidores Enzimáticos/uso terapêutico , Ácido Micofenólico/uso terapêutico , Dermatopatias/tratamento farmacológico , Adolescente , Diagnóstico Diferencial , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imuno-Histoquímica , Pele/patologia
8.
Prenat Diagn ; 38(1): 33-43, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29096039

RESUMO

OBJECTIVE: Rare genetic disorders resulting in prenatal or neonatal death are genetically heterogeneous, but testing is often limited by the availability of fetal DNA, leaving couples without a potential prenatal test for future pregnancies. We describe our novel strategy of exome sequencing parental DNA samples to diagnose recessive monogenic disorders in an audit of the first 50 couples referred. METHOD: Exome sequencing was carried out in a consecutive series of 50 couples who had 1 or more pregnancies affected with a lethal or prenatal-onset disorder. In all cases, there was insufficient DNA for exome sequencing of the affected fetus. Heterozygous rare variants (MAF < 0.001) in the same gene in both parents were selected for analysis. Likely, disease-causing variants were tested in fetal DNA to confirm co-segregation. RESULTS: Parental exome analysis identified heterozygous pathogenic (or likely pathogenic) variants in 24 different genes in 26/50 couples (52%). Where 2 or more fetuses were affected, a genetic diagnosis was obtained in 18/29 cases (62%). In most cases, the clinical features were typical of the disorder, but in others, they result from a hypomorphic variant or represent the most severe form of a variable phenotypic spectrum. CONCLUSION: We conclude that exome sequencing of parental samples is a powerful strategy with high clinical utility for the genetic diagnosis of lethal or prenatal-onset recessive disorders. © 2017 The Authors Prenatal Diagnosis published by John Wiley & Sons Ltd.


Assuntos
Anormalidades Congênitas/genética , Doenças Genéticas Inatas/diagnóstico , Pais , Diagnóstico Pré-Natal/métodos , Sequenciamento Completo do Exoma , Feminino , Genes Recessivos , Humanos , Masculino , Gravidez
9.
J Med Genet ; 55(2): 104-113, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29097605

RESUMO

BACKGROUND: De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. OBJECTIVES: To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. METHODS: Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotype-phenotype correlations by analysis of both recurrent mutations as well as mutation classes. RESULTS: We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. CONCLUSION: We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.

10.
12.
Pediatr Dev Pathol ; 20(4): 340-347, 2017 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28727976

RESUMO

Monozygotic twins with discordant karyotypes for trisomy 13 are rare. We report a case of a spontaneously conceived pregnancy who presented with first-trimester ultrasound finding of umbilical cord cyst and increased nuchal translucency in Twin A and no abnormalities in Twin B. Amniocentesis revealed 47,XY,+13 karyotype in Twin A and 46,XY karyotype in Twin B. Selective fetal reduction was performed for Twin A. Twin B was delivered at 32 weeks gestation with normal phenotype. Peripheral blood karyotype revealed 15% mosaicism for trisomy 13 and skin fibroblast revealed 46,XY karyotype. The surviving twin will be monitored for potential complication of uniparental disomy 13 and mosaic trisomy 13. This case reinforces the need for early ultrasound and nuchal translucency measurements, especially in twin gestations.

13.
Med Clin North Am ; 101(4): 807-821, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28577628

RESUMO

The burden of depression in the United States is substantial. Evidence supports the benefits of screening for depression in all adults, including older patients and pregnant and postpartum women, when coupled with appropriate resources for management of disease. Developing, implementing, and sustaining a high-fidelity screening process is an important first step for improving the care of patients with depression in primary care. Initial treatment for depression should include psychotherapy, pharmacotherapy, or a combination of both. Collaborative care models are evidence-based approaches to depression treatment and follow-up that can be feasibly initiated in the primary care setting.


Assuntos
Depressão/diagnóstico , Programas de Rastreamento/organização & administração , Atenção Primária à Saúde/organização & administração , Fatores Etários , Antidepressivos/uso terapêutico , Depressão/epidemiologia , Depressão/terapia , Depressão Pós-Parto/diagnóstico , Feminino , Humanos , Programas de Rastreamento/métodos , Psicoterapia , Fatores Sexuais , Estados Unidos
14.
Nat Genet ; 49(7): 1148-1151, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28553959

RESUMO

Through exome sequencing, we identified six individuals with biallelic loss-of-function mutations in TRIP13. All six developed Wilms tumor. Constitutional mosaic aneuploidies, microcephaly, developmental delay and seizures, which are features of mosaic variegated aneuploidy (MVA) syndrome, were more variably present. Through functional studies, we show that TRIP13-mutant patient cells have no detectable TRIP13 and have substantial impairment of the spindle assembly checkpoint (SAC), leading to a high rate of chromosome missegregation. Accurate segregation, as well as SAC proficiency, is rescued by restoring TRIP13 function. Individuals with biallelic TRIP13 or BUB1B mutations have a high risk of embryonal tumors, and here we show that their cells display severe SAC impairment. MVA due to biallelic CEP57 mutations, or of unknown cause, is not associated with embryonal tumors and cells from these individuals show minimal SAC deficiency. These data provide insights into the complex relationships between aneuploidy and carcinogenesis.


Assuntos
Proteínas de Transporte/genética , Segregação de Cromossomos/genética , Neoplasias Renais/genética , Pontos de Checagem da Fase M do Ciclo Celular/genética , Tumor de Wilms/genética , ATPases Associadas a Diversas Atividades Celulares , Aneuploidia , Proteínas de Ciclo Celular/genética , Pré-Escolar , DNA de Neoplasias/genética , Deficiências do Desenvolvimento/genética , Feminino , Predisposição Genética para Doença , Humanos , Leucemia Mieloide Aguda/genética , Microcefalia/genética , Proteínas Associadas aos Microtúbulos/genética , Mosaicismo , Mutação , Neoplasias Primárias Múltiplas/genética , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Proteínas Serina-Treonina Quinases/genética , Estabilidade de RNA/genética , Convulsões/genética , Tumor de Células de Sertoli-Leydig/genética
15.
Eur J Hum Genet ; 25(5): 552-559, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28327570

RESUMO

PUF60 encodes a nucleic acid-binding protein, a component of multimeric complexes regulating RNA splicing and transcription. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects. Very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome. We report 12 additional patients with PUF60 variants who were ascertained using exome sequencing: six through the Deciphering Developmental Disorders Study and six through similar projects. Detailed phenotypic analysis of all patients was undertaken. All 12 patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing: four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. Analysis of cDNA from a fibroblast cell line derived from one of the patients with an ESS variants revealed aberrant splicing. The consistent feature was developmental delay and most patients had short stature. The phenotypic variability was striking; however, we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney. Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function.


Assuntos
Anormalidades Múltiplas/genética , Deficiência Intelectual/genética , Microcefalia/genética , Mutação de Sentido Incorreto , Fatores de Processamento de RNA/genética , Proteínas Repressoras/genética , Anormalidades Múltiplas/diagnóstico , Células Cultivadas , Criança , Códon de Terminação/genética , Exoma , Feminino , Heterozigoto , Humanos , Deficiência Intelectual/diagnóstico , Masculino , Microcefalia/diagnóstico , Fenótipo , Síndrome
16.
Australas J Dermatol ; 58(2): 155-159, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28251611

RESUMO

Although most infantile haemangiomas do not require treatment due to a natural history of spontaneous involution, some require early intervention. The Australasian Vascular Anomalies Network and the Australasian Paediatric Dermatology Network have developed a consensus statement for the treatment of infantile haemangiomas with oral propranolol. Infants with haemangiomas that are life threatening, at risk of ulceration, or at risk of causing a significant functional impairment, psychological impact or physical deformity should be treated early with oral propranolol. Oral propranolol is safe and effective and in most healthy infants oral propranolol can be started in an outpatient setting.


Assuntos
Consenso , Hemangioma Capilar/tratamento farmacológico , Síndromes Neoplásicas Hereditárias/tratamento farmacológico , Propranolol/uso terapêutico , Vasodilatadores/uso terapêutico , Monitoramento de Medicamentos , Humanos , Seleção de Pacientes , Propranolol/administração & dosagem , Vasodilatadores/administração & dosagem
18.
Am J Med Genet A ; 170(11): 2835-2846, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27667800

RESUMO

KBG syndrome is characterized by short stature, distinctive facial features, and developmental/cognitive delay and is caused by mutations in ANKRD11, one of the ankyrin repeat-containing cofactors. We describe 32 KBG patients aged 2-47 years from 27 families ascertained via two pathways: targeted ANKRD11 sequencing (TS) in a group who had a clinical diagnosis of KBG and whole exome sequencing (ES) in a second group in whom the diagnosis was unknown. Speech delay and learning difficulties were almost universal and variable behavioral problems frequent. Macrodontia of permanent upper central incisors was seen in 85%. Other clinical features included short stature, conductive hearing loss, recurrent middle ear infection, palatal abnormalities, and feeding difficulties. We recognized a new feature of a wide anterior fontanelle with delayed closure in 22%. The subtle facial features of KBG syndrome were recognizable in half the patients. We identified 20 ANKRD11 mutations (18 novel: all truncating) confirmed by Sanger sequencing in 32 patients. Comparison of the two ascertainment groups demonstrated that facial/other typical features were more subtle in the ES group. There were no conclusive phenotype-genotype correlations. Our findings suggest that mutation of ANKRD11 is a common Mendelian cause of developmental delay. Affected patients may not show the characteristic KBG phenotype and the diagnosis is therefore easily missed. We propose updated diagnostic criteria/clinical recommendations for KBG syndrome and suggest that inclusion of ANKRD11 will increase the utility of gene panels designed to investigate developmental delay. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Anormalidades Dentárias/diagnóstico , Anormalidades Dentárias/genética , Deleção Cromossômica , Cromossomos Humanos Par 16 , Hibridização Genômica Comparativa , Facies , Feminino , Humanos , Masculino , Fenótipo , Proteínas Repressoras/genética
19.
Pediatr Dev Pathol ; 2016 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-27018625

RESUMO

Monozygotic twins with discordant karyotypes for trisomy 13 are rare. We report a case of a spontaneously conceived pregnancy who presented with first trimester ultrasound finding of umbilical cord cyst and increased nuchal translucency in Twin A and no abnormalities in Twin B. Amniocentesis revealed 47,XY,+13 karyotype in Twin A and 46,XY karyotype in Twin B. Selective fetal reduction was performed for Twin A. Twin B was delivered at 32 weeks gestation with normal phenotype. Peripheral blood karyotype revealed 15% mosaicism for trisomy 13 and skin fibroblast revealed 46,XY karyotype. The surviving twin will be monitored for potential complication of uniparental disomy 13 and mosaic trisomy 13. This case reinforces the need for early ultrasound and nuchal translucency measurements, especially in twin gestations.

20.
PLoS One ; 11(3): e0150555, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26974433

RESUMO

Axial spondylometaphyseal dysplasia (axial SMD) is an autosomal recessive disease characterized by dysplasia of axial skeleton and retinal dystrophy. We conducted whole exome sequencing and identified C21orf2 (chromosome 21 open reading frame 2) as a disease gene for axial SMD. C21orf2 mutations have been recently found to cause isolated retinal degeneration and Jeune syndrome. We found a total of five biallelic C21orf2 mutations in six families out of nine: three missense and two splicing mutations in patients with various ethnic backgrounds. The pathogenic effects of the splicing (splice-site and branch-point) mutations were confirmed on RNA level, which showed complex patterns of abnormal splicing. C21orf2 mutations presented with a wide range of skeletal phenotypes, including cupped and flared anterior ends of ribs, lacy ilia and metaphyseal dysplasia of proximal femora. Analysis of patients without C21orf2 mutation indicated genetic heterogeneity of axial SMD. Functional data in chondrocyte suggest C21orf2 is implicated in cartilage differentiation. C21orf2 protein was localized to the connecting cilium of the cone and rod photoreceptors, confirming its significance in retinal function. Our study indicates that axial SMD is a member of a unique group of ciliopathy affecting skeleton and retina.


Assuntos
Doenças Genéticas Inatas/genética , Mutação , Osteocondrodisplasias/genética , Proteínas/genética , Adolescente , Cartilagem/metabolismo , Cartilagem/patologia , Diferenciação Celular/genética , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica , Doenças Genéticas Inatas/diagnóstico por imagem , Doenças Genéticas Inatas/metabolismo , Humanos , Masculino , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/metabolismo , Fenótipo , Proteínas/metabolismo , Radiografia , Retina/metabolismo , Retina/patologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA