Re: this information was sent to me

[Guest guest]

Hi - where is this particular reference from? These data

come from you all - it is the Baylor CHARGE gene study that Dr. Seema

Lalani has been doing. Dr. Belmont started the study, drawing

blood on kids with CHARGE and their parents at the 1999 Houston

conference. They didn't find the gene first, but once CHD7 was found

to be a cause of CHARGE, they tested all their samples for CHD7

mutations. The first go-around found mutations in 64/110 samples.

And the (not yet published, but really exciting) update is that CHD7

mutations have now been found in even more of the 110 subjects - as

the techniques for doing the test gets better, they are finding more

kids to be " positive " for mutations!

For a long, complete (written for doctors, but you'll get most of it)

discussion of CHARGE, go to www.genetests.org and look up the

GeneReview on CHARGE.

Meg

Meg Hefner

Genetic Counselor

St. Louis MO

>

> i have more if you want it

>

> CHARGE syndrome (MIM 214800) is a distinctive syndrome with a complex

> constellation of multiple congenital anomalies. The incidence of

> CHARGE syndrome may be as high as 1 in 8, 500 births (Issekutz et al.

> 2005). It is characterized by variable occurrence of coloboma,

> choanal atresia or cleft lip and/or palate, cranial nerve

> dysfunction, characteristic external ear malformations with distinct

> temporal bone anomalies, cardiovascular malformations, and

> hypogonadotropic hypogonadism with genitourinary anomalies (Hall

> 1979; Hittner et al. 1979; Pagon et al. 1981; Blake et al. 1998).

> Inner ear defects, including Mondini malformation and/or semicircular

> canal hypoplasia/aplasia are common and often cause hearing loss and

> vestibular abnormalities in the affected individuals (Amiel et al.

> 2001). Many types of cardiovascular malformations have been reported,

> but conotruncal and aortic arch malformations appear to be more

> common than the others (Blake et al. 1998). Growth delay, distinctive

> facial features, Di sequence, and tracheoesophageal fistula are

> some of the additional clinical features of this condition. In the 25

> years since its initial characterization, the diagnostic criteria for

> the original CHARGE acronym were revised and standardized (Blake et

> al. 1998), with a further proposal to update them (Verloes 2005).

> What was considered a prototypic " association " is now viewed as a

> syndrome in many well-defined cases (Lubinsky 1994), for which the

> name " Hall-Hittner syndrome " may also apply (Graham 2001). Vissers et

> al. (2004) reported mutations in the CHD7 gene, which encodes

> chromodomain helicase DNA-binding protein, in ~60% of individuals

> with CHARGE syndrome. Chromatin remodeling is a recognized mechanism

> of gene-expression regulation, and the CHD7 gene is likely to play a

> significant role in embryonic development and cell-cycle regulation

> (Woodage et al. 1997). The prevalence of CHD7 mutations in a large

> cohort of individuals with CHARGE syndrome and the possible

> correlation of specific mutations with clinical characteristics have

> not been formally addressed. We report the systematic molecular and

> phenotypic evaluation of 110 individuals with clinical CHARGE

> syndrome. We identified mutations in the CHD7 gene in 58% (64/110) of

> the affected individuals and analyzed the phenotypic data of the

> study cohort, using multivariate analysis conditional on the mutation

> status. Our results indicate significant phenotypic differences

> between CHD7 mutation carriers and noncarriers and are consistent

> with locus heterogeneity as the likely explanation for the group of

> individuals with CHARGE syndrome whose sequence analysis of CHD7 was

> normal. Nucleotide sequence data reported herein are available in the

> DDBJ/EMBL/GenBank databases; for details, see the Web Resources

> section.

>

[Guest guest]

The URL for that review is:

http://genetests.org/servlet/access?db=geneclinics & site=gt & id=8888891 & key=ObZ8mm\

T-gfTvf & gry= & fcn=y & fw=wQMA & filename=/profiles/charge/index.html

(who should be studying for a psychology exam but is reading CHARGE

genereview article instead!)

www.chargesyndrome.info

>

> Hi - where is this particular reference from? These data

> come from you all - it is the Baylor CHARGE gene study that Dr. Seema

> Lalani has been doing. Dr. Belmont started the study, drawing

> blood on kids with CHARGE and their parents at the 1999 Houston

> conference. They didn't find the gene first, but once CHD7 was found

> to be a cause of CHARGE, they tested all their samples for CHD7

> mutations. The first go-around found mutations in 64/110 samples.

>

> And the (not yet published, but really exciting) update is that CHD7

> mutations have now been found in even more of the 110 subjects - as

> the techniques for doing the test gets better, they are finding more

> kids to be " positive " for mutations!

>

> For a long, complete (written for doctors, but you'll get most of it)

> discussion of CHARGE, go to www.genetests.org and look up the

> GeneReview on CHARGE.

> Meg

>

> Meg Hefner

> Genetic Counselor

> St. Louis MO

>

>

> >

> > i have more if you want it

> >

> > CHARGE syndrome (MIM 214800) is a distinctive syndrome with a complex

> > constellation of multiple congenital anomalies. The incidence of

> > CHARGE syndrome may be as high as 1 in 8, 500 births (Issekutz et al.

> > 2005). It is characterized by variable occurrence of coloboma,

> > choanal atresia or cleft lip and/or palate, cranial nerve

> > dysfunction, characteristic external ear malformations with distinct

> > temporal bone anomalies, cardiovascular malformations, and

> > hypogonadotropic hypogonadism with genitourinary anomalies (Hall

> > 1979; Hittner et al. 1979; Pagon et al. 1981; Blake et al. 1998).

> > Inner ear defects, including Mondini malformation and/or semicircular

> > canal hypoplasia/aplasia are common and often cause hearing loss and

> > vestibular abnormalities in the affected individuals (Amiel et al.

> > 2001). Many types of cardiovascular malformations have been reported,

> > but conotruncal and aortic arch malformations appear to be more

> > common than the others (Blake et al. 1998). Growth delay, distinctive

> > facial features, Di sequence, and tracheoesophageal fistula are

> > some of the additional clinical features of this condition. In the 25

> > years since its initial characterization, the diagnostic criteria for

> > the original CHARGE acronym were revised and standardized (Blake et

> > al. 1998), with a further proposal to update them (Verloes 2005).

> > What was considered a prototypic " association " is now viewed as a

> > syndrome in many well-defined cases (Lubinsky 1994), for which the

> > name " Hall-Hittner syndrome " may also apply (Graham 2001). Vissers et

> > al. (2004) reported mutations in the CHD7 gene, which encodes

> > chromodomain helicase DNA-binding protein, in ~60% of individuals

> > with CHARGE syndrome. Chromatin remodeling is a recognized mechanism

> > of gene-expression regulation, and the CHD7 gene is likely to play a

> > significant role in embryonic development and cell-cycle regulation

> > (Woodage et al. 1997). The prevalence of CHD7 mutations in a large

> > cohort of individuals with CHARGE syndrome and the possible

> > correlation of specific mutations with clinical characteristics have

> > not been formally addressed. We report the systematic molecular and

> > phenotypic evaluation of 110 individuals with clinical CHARGE

> > syndrome. We identified mutations in the CHD7 gene in 58% (64/110) of

> > the affected individuals and analyzed the phenotypic data of the

> > study cohort, using multivariate analysis conditional on the mutation

> > status. Our results indicate significant phenotypic differences

> > between CHD7 mutation carriers and noncarriers and are consistent

> > with locus heterogeneity as the likely explanation for the group of

> > individuals with CHARGE syndrome whose sequence analysis of CHD7 was

> > normal. Nucleotide sequence data reported herein are available in the

> > DDBJ/EMBL/GenBank databases; for details, see the Web Resources

> > section.

> >

>

>

>

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" It is far better to grasp the universe as it really is than to persist in

delusion, however satisfying and reassuring. " --Carl Sagan