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
Validation

Diseases presenting "mental retardation" symptom

achondroplasia

alexander disease

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

classical phenylketonuria

coats disease

cohen syndrome

cowden syndrome

cystinuria

dentin dysplasia

familial hypocalciuric hypercalcemia

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

lamellar ichthyosis

lymphangioleiomyomatosis

monosomy 21

phenylketonuria

primary hyperoxaluria type 1

proteus syndrome

pyruvate dehydrogenase deficiency

sneddon syndrome

triple a syndrome

wolf-hirschhorn syndrome

zellweger syndrome

This symptom has already been validated