Protein-elongating mutations in MYH11 are implicated in a dominantly inherited smooth muscle dysmotility syndrome with severe esophageal, gastric, and intestinal disease.
Hum Mutat
; 41(5): 973-982, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-31944481
ABSTRACT
Gastrointestinal motility disorders include a spectrum of mild to severe clinical phenotypes that are caused by smooth muscle dysfunction. We investigated the genetic etiology of severe esophageal, gastric, and colonic dysmotility in two unrelated families with autosomal dominant disease presentation. Using exome sequencing, we identified a 2 base pair insertion at the end of the myosin heavy chain 11 (MYH11) gene in all affected members of Family 1 [NM_001040113c.5819_5820insCA(p.Gln1941Asnfs*91)] and a 1 base pair deletion at the same genetic locus in Proband 2 [NM_001040113c.5819del(p.Pro1940Hisfs*91)]. Both variants are predicted to result in a similarly elongated protein product. Heterozygous dominant negative MYH11 pathogenic variants have been associated with thoracic aortic aneurysm and dissection while biallelic null alleles have been associated with megacystis microcolon intestinal hypoperistalsis syndrome. This report highlights heterozygous protein-elongating MYH11 variants affecting the SM2 isoforms of MYH11 as a cause for severe gastrointestinal dysmotility, and we hypothesize that the mechanistic pathogenesis of this disease, dominant hypercontractile loss-of-function, is distinct from those implicated in other diseases involving MYH11 dysfunction.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Cadenas Pesadas de Miosina
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Predisposición Genética a la Enfermedad
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Estudios de Asociación Genética
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Músculo Liso
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Mutación
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
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Child
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Female
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Humans
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Infant
/
Male
/
Middle aged
Idioma:
En
Revista:
Hum Mutat
Asunto de la revista:
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article