A homozygous loss-of-function variant in MYH11 in a case with megacystis-microcolon-intestinal hypoperistalsis syndrome.
Eur J Hum Genet
; 23(9): 1266-8, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-25407000
ABSTRACT
Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is characterized by marked dilatation of the bladder and microcolon and decreased intestinal peristalsis. Recent studies indicate that heterozygous variants in ACTG2, which codes for a smooth muscle actin, cause MMIHS. However, such variants do not explain MMIHS cases that show an autosomal recessive mode of inheritance. We performed exome sequencing in a newborn with MMIHS and prune belly phenotype whose parents are consanguineous and identified a homozygous variant (c.3598A>T p.Lys1200Ter) in MYH11, which codes for the smooth muscle myosin heavy chain. Previous studies showed that loss of Myh11 function in mice causes a bladder and intestinal phenotype that is highly reminiscent of MMIHS. All together, these observations strongly suggest that loss-of-function variants in MYH11 cause MMIHS. The documentation of variants in ACTG2 and MYH11 thus points to the involvement of the contractile apparatus of the smooth muscle in MMIHS. Interestingly, dominant-negative variants in MYH11 have previously been shown to cause thoracic aortic aneurism and dilatation. Different mechanisms of MYH11 disruption may thus lead to distinct patterns of smooth muscle dysfunction.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Síndrome del Abdomen en Ciruela Pasa
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Anomalías Múltiples
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Vejiga Urinaria
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Seudoobstrucción Intestinal
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Colon
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Cadenas Pesadas de Miosina
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Homocigoto
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Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Humans
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Male
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Newborn
Idioma:
En
Revista:
Eur J Hum Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Canadá