Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
1.
Am J Med Genet A ; 191(6): 1614-1618, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36891747

RESUMO

Ethylmalonic encephalopathy (EE) is a rare, severe, autosomal recessive condition caused by pathogenic variants in ETHE1 leading to progressive encephalopathy, hypotonia evolving to dystonia, petechiae, orthostatic acrocyanosis, diarrhea, and elevated ethylmalonic acid in urine. In this case report, we describe a patient with only mild speech and gross motor delays, subtle biochemical abnormalities, and normal brain imaging found to be homozygous for a pathogenic ETHE1 variant (c.586G>A) via whole exome sequencing. This case highlights the clinical heterogeneity of ETHE1 mutations and the utility of whole-exome sequencing in diagnosing mild cases of EE.


Assuntos
Encefalopatias Metabólicas Congênitas , Encefalopatias , Púrpura , Humanos , Encefalopatias Metabólicas Congênitas/diagnóstico , Encefalopatias Metabólicas Congênitas/genética , Púrpura/diagnóstico , Púrpura/genética , Encéfalo/patologia , Encefalopatias/diagnóstico , Encefalopatias/genética , Encefalopatias/patologia , Proteínas Mitocondriais/genética , Proteínas de Transporte Nucleocitoplasmático/genética
2.
Brain ; 143(1): 55-68, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834374

RESUMO

MN1 encodes a transcriptional co-regulator without homology to other proteins, previously implicated in acute myeloid leukaemia and development of the palate. Large deletions encompassing MN1 have been reported in individuals with variable neurodevelopmental anomalies and non-specific facial features. We identified a cluster of de novo truncating mutations in MN1 in a cohort of 23 individuals with strikingly similar dysmorphic facial features, especially midface hypoplasia, and intellectual disability with severe expressive language delay. Imaging revealed an atypical form of rhombencephalosynapsis, a distinctive brain malformation characterized by partial or complete loss of the cerebellar vermis with fusion of the cerebellar hemispheres, in 8/10 individuals. Rhombencephalosynapsis has no previously known definitive genetic or environmental causes. Other frequent features included perisylvian polymicrogyria, abnormal posterior clinoid processes and persistent trigeminal artery. MN1 is encoded by only two exons. All mutations, including the recurrent variant p.Arg1295* observed in 8/21 probands, fall in the terminal exon or the extreme 3' region of exon 1, and are therefore predicted to result in escape from nonsense-mediated mRNA decay. This was confirmed in fibroblasts from three individuals. We propose that the condition described here, MN1 C-terminal truncation (MCTT) syndrome, is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein. Our data show that MN1 plays a critical role in human craniofacial and brain development, and opens the door to understanding the biological mechanisms underlying rhombencephalosynapsis.


Assuntos
Anormalidades Múltiplas/genética , Anormalidades Craniofaciais/genética , Deficiência Intelectual/genética , Transtornos do Desenvolvimento da Linguagem/genética , Malformações do Sistema Nervoso/genética , Transativadores/genética , Proteínas Supressoras de Tumor/genética , Anormalidades Múltiplas/diagnóstico por imagem , Adolescente , Artéria Basilar/anormalidades , Artéria Basilar/diagnóstico por imagem , Artérias Carótidas/anormalidades , Artérias Carótidas/diagnóstico por imagem , Vermis Cerebelar/anormalidades , Vermis Cerebelar/diagnóstico por imagem , Cerebelo/anormalidades , Cerebelo/diagnóstico por imagem , Criança , Pré-Escolar , Estudos de Coortes , Hibridização Genômica Comparativa , Anormalidades Craniofaciais/diagnóstico por imagem , Feminino , Fibroblastos/metabolismo , Humanos , Imageamento Tridimensional , Lactente , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Malformações do Sistema Nervoso/diagnóstico por imagem , Degradação do RNAm Mediada por Códon sem Sentido , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/genética , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , Síndrome , Tomografia Computadorizada por Raios X , Sequenciamento do Exoma , Sequenciamento Completo do Genoma
3.
Genes (Basel) ; 14(3)2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36980998

RESUMO

The Multidisciplinary Ophthalmic Genetics Clinic (MOGC) at the University of Michigan Kellogg Eye Center aims to provide medical and ophthalmic genetics care to patients with inherited ocular conditions. We have developed a clinical and referral workflow where each patient undergoes coordinated evaluation by our multidisciplinary team followed by discussions on diagnosis, prognosis, and genetic testing. Testing approaches are specific to each patient and can be targeted (single-gene, gene panel), broad (chromosomal microarray, whole-exome sequencing), or a combination. We hypothesize that this clinic model improves patient outcomes and quality of care. A retrospective chart review of patients in the MOGC from July 2020 to October 2022 revealed that the most common referral diagnoses were congenital cataracts, optic neuropathy, and microphthalmia, with 52% syndromic cases. Within this patient cohort, we saw a 76% uptake for genetic testing, among which 33% received a diagnostic test result. Our results support a tailored approach to genetic testing for specific conditions. Through case examples, we highlight the power and impact of our clinic. By integrating ophthalmic care with medical genetics and counseling, the MOGC has not only helped solve individual patient diagnostic challenges but has aided the greater population in novel genetic discoveries and research towards targeted therapeutics.


Assuntos
Microftalmia , Doenças do Nervo Óptico , Humanos , Estudos Retrospectivos , Testes Genéticos , Olho
4.
Mol Syndromol ; 10(6): 327-331, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32021607

RESUMO

Interstitial and terminal deletions of chromosome 4q have been described for many years and have variable phenotypes depending on the size of the deletion present. Clinical features can include developmental delay, growth difficulty, digital differences, dysmorphic features, and cardiac anomalies. Here, we present an infant with pseudohypoaldosteronism found to have a deletion of 4q31.21q31.23, including NR3C2. Heterozygous mutations in NR3C2 have been reported to cause autosomal dominant pseudohypoaldosteronism type 1 (PHA1A). This represents a rare case of PHA1A due to a contiguous interstitial deletion and highlights the importance of evaluating patients with overlapping deletions for PHA1A.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA