| [PMID]: | 28259707 |
| [Au] Autor: | Bryan MM; Tolman NJ; Simon KL; Huizing M; Hufnagel RB; Brooks BP; Speransky V; Mullikin JC; Gahl WA; Malicdan MC; Gochuico BR |
| [Ad] Endereço: | Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. |
| [Ti] Título: | Clinical and molecular phenotyping of a child with Hermansky-Pudlak syndrome-7, an uncommon genetic type of HPS. |
| [So] Source: | Mol Genet Metab;120(4):378-383, 2017 Apr. |
| [Is] ISSN: | 1096-7206 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | PURPOSE: Hermansky-Pudlak syndrome (HPS) is a rare inherited disorder with ten reported genetic types; each type has defects in subunits of either Adaptor Protein-3 complex or Biogenesis of Lysosome-related Organelles Complex (BLOC)-1, -2, or -3. Very few patients with BLOC-1 deficiency (HPS-7, -8, and -9 types) have been diagnosed. We report results of comprehensive clinical testing and molecular analyses of primary fibroblasts from a new case of HPS-7. RESULTS: A 6-year old Paraguayan male presented with hypopigmentation, ocular albinism, nystagmus, reduced visual acuity, and easy bruising. He also experienced delayed motor and language development as a very young child; head and chest trauma resulted in intracranial hemorrhage with subsequent right hemiparesis and lung scarring. There was no clinical evidence of immunodeficiency or colitis. Whole mount transmission electron microscopy revealed absent platelet delta granules; platelet aggregation testing was abnormal. Exome sequencing revealed a homozygous nonsense mutation in the Dystrobrevin binding protein 1 (DTNBP1) gene [NM_032122.4: c.307C>T; p.Gln103*], previously reported in a Portuguese adult. The gene encodes the dysbindin subunit of BLOC-1. Dysbindin protein expression was negligible in our patient's dermal fibroblasts, while his DTNBP1 mRNA level was similar to that of a normal control. CONCLUSIONS: Comprehensive clinical evaluation of the first pediatric case reported with HPS-7 reveals oculocutaneous albinism and platelet storage pool deficiency; his phenotype is consistent with findings in other patients with BLOC-1 disorders. This patient's markedly reduced Dysbindin protein expression in HPS-7 resulted from a mechanism other than nonsense mediated decay. |
| [Mh] Termos MeSH primário: |
Códon sem Sentido
Proteínas Associadas à Distrofina/genética
Síndrome de Hermanski-Pudlak/patologia
|
| [Mh] Termos MeSH secundário: |
Criança
Disbindina
Proteínas Associadas à Distrofina/metabolismo
Exoma
Síndrome de Hermanski-Pudlak/genética
Síndrome de Hermanski-Pudlak/metabolismo
Seres Humanos
Masculino
Análise de Sequência de DNA
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| [Pt] Tipo de publicação: | CASE REPORTS; JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Codon, Nonsense); 0 (DTNBP1 protein, human); 0 (Dysbindin); 0 (Dystrophin-Associated Proteins) |
| [Em] Mês de entrada: | 1708 |
| [Cu] Atualização por classe: | 171116 |
[Lr] Data última revisão:
| 171116 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 170306 |
| [St] Status: | MEDLINE |
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