Mutational spectrum of COH1 and clinical heterogeneity in Cohen syndrome.

[cohen syndrome]

Cohen syndrome (CS ) is an autosomal recessive disorder with variability in the clinical manifestations , characterised by mental retardation , postnatal microcephaly , facial dysmorphism , pigmentary retinopathy , myopia , and intermittent neutropenia . Mutations in the gene COH 1 have been found in an ethnically diverse series of patients . Brief clinical descriptions of 24 patients with CS are provided . The patients were from 16 families of different ethnic backgrounds and between 2 .5 and 60 years of age at assessment . DNA samples from all patients were analysed for mutations in COH 1 by direct sequencing . Splice site mutations were characterised using reverse transcriptase PCR analysis from total RNA samples . In this series , we detected 25 different COH 1 mutations ; 19 of these were novel , including 9 nonsense mutations , 8 frameshift mutations , 4 verified splice site mutations , 3 larger in frame deletions , and 1 missense mutation . We observed marked variability of developmental and growth parameters . The typical facial gestalt was seen in 23 /24 patients . Early onset progressive myopia was present in all the patients older than 5 years . Widespread pigmentary retinopathy was found in 12 /14 patients assessed over 5 years of age . We present evidence for extended allelic heterogeneity of CS , with the vast majority of mutations leading to premature termination codons in COH 1 . Our data confirm the broad clinical spectrum of CS with some patients lacking even the characteristic facial gestalt and pigmentary retinopathy at school age .

Diseases
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Diseases presenting "premature termination codons" symptom

cohen syndrome

dystrophic epidermolysis bullosa

harlequin ichthyosis

homocystinuria without methylmalonic aciduria

junctional epidermolysis bullosa

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