Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here on a RAB23 mutation (c.86dupA) present in the homozygote state in four relatives of Comorian origin with Carpenter syndrome. All children presented with acrocephaly and polysyndactyly. However, intrafamilial variability was observed with variable severity of craniosynostosis ranging from cloverleaf skull to predominant involvement of the metopic ridge. All children also presented with a combination of brachydactyly with agenesis of the middle phalanges, syndactyly, broad thumbs, and postaxial polydactyly (2/4) in the hands, and preaxial polydactyly (3) and syndactyly (4) in the toes. Mental development was normal in all four children but the eldest one presented with impaired motor development as a result of orthopedic complications. Brain imaging showed hydrocephalus in 2/4 and additional features included genu valgum (2/4), abnormal genitalia (3/4), corneal anomaly (2/4), umbilical hernia (1/4), severe cyphoscoliosis (1), patent ductus arteriosus (1/4), and accessory spleen (1). In contrast to previous reports, growth was below average except for one patient and the eldest one became moderately overweight with time. We conclude from the report of this large unique family with four affected children that Carpenter syndrome is a genetically homogenous but a clinically variable condition.
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PMID:RAB23 mutation in a large family from Comoros Islands with Carpenter syndrome. 2035 13

Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed.
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PMID:Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization. 2306 20