Homozygous variants in the HEXB and MBOAT7 genes underlie neurological diseases in consanguineous families.
BMC Med Genet
; 20(1): 199, 2019 12 18.
Article
em En
| MEDLINE
| ID: mdl-31852446
BACKGROUND: Neurological disorders are a common cause of morbidity and mortality within Pakistani populations. It is one of the most important challenges in healthcare, with significant life-long socio-economic burden. METHODS: We investigated the cause of disease in three Pakistani families in individuals with unexplained autosomal recessive neurological conditions, using both genome-wide SNP mapping and whole exome sequencing (WES) of affected individuals. RESULTS: We identified a homozygous splice site variant (NM_000521:c.445 + 1G > T) in the hexosaminidase B (HEXB) gene confirming a diagnosis of Sandhoff disease (SD; type II GM2-gangliosidosis), an autosomal recessive lysosomal storage disorder caused by deficiency of hexosaminidases in a single family. In two further unrelated families, we identified a homozygous frameshift variant (NM_024298.3:c.758_778del; p.Glu253_Ala259del) in membrane-bound O-acyltransferase family member 7 (MBOAT7) as the likely cause of disease. MBOAT7 gene variants have recently been identified as a cause of intellectual disability (ID), seizures and autistic features. CONCLUSIONS: We identified two metabolic disorders of lipid biosynthesis within three Pakistani families presenting with undiagnosed neurodevelopmental conditions. These findings enabled an accurate neurological disease diagnosis to be provided for these families, facilitating disease management and genetic counselling within this population. This study consolidates variation within MBOAT7 as a cause of neurodevelopmental disorder, broadens knowledge of the clinical outcomes associated with MBOAT7-related disorder, and confirms the likely presence of a regionally prevalent founder variant (c.758_778del; p.Glu253_Ala259del) in Pakistan.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aciltransferases
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Cadeia beta da beta-Hexosaminidase
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Homozigoto
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Proteínas de Membrana
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Doenças do Sistema Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Infant
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Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
BMC Med Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Paquistão