De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy.
Am J Med Genet A
; 176(12): 2623-2629, 2018 12.
Article
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| MEDLINE
| ID: mdl-30151950
ABSTRACT
KIF26B is a member of the kinesin superfamily with evolutionarily conserved functions in controlling aspects of embryogenesis, including the development of the nervous system, though its function is incompletely understood. We describe an infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. We performed whole exome sequencing on the trio and identified a de novo KIF26B missense variant, p.Gly546Ser, in the proband. This variant alters a highly conserved amino acid residue that is part of the phosphate-binding loop motif and motor-like domain and is deemed pathogenic by several in silico methods. Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity. Overall, KIF26B may play a critical role in the brain development and, when mutated, cause pontocerebellar hypoplasia with arthrogryposis.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Atrofias Olivopontocerebelosas
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Atrofias Musculares Espinales de la Infancia
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Cinesinas
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Am J Med Genet A
Asunto de la revista:
GENETICA MEDICA
Año:
2018
Tipo del documento:
Article