Athena Labs testing 6 mtDNA MELAS mutations?? was: Re: lots of melas ?

[Guest guest]

Hi Steve,

This is amazing. All the Mito doctors that I have spoken to or emailed have all

told me that there are only 2 maybe 3 mtDNA mutations for MELAS.

In my opinion the Athena Lab is NOT on the up and up. Too many problems with the

company, screwed up lab results, missing blood, testing for the wrong panels,

etc... If they are testing for 6 mutations of MELAS how come no other Lab is

testing for that many? Did Athena some how discover the extra mutations on their

own. hehehe!!!

So if Athena isn't the only Lab testing for this many MELAS mutations, someone

please let me know what over labs are testing for all 6.

Maybe I am wrong and I am not up to date with the latest MELAS information. If

this is the case someone let me know so I don't make the same mistake again.

Thanks

Hugs,

Ann-Marie

lots of melas ?

it seems as though an awful lot of people (adults with mito) at least from

this list have melas ! can anyone hazard a guess as to % ?

----- Original Message -----

[Guest guest]

Got curious about MELAS mutations, so here's excerpts from a few sites below. I

have first hand experience with some questionable handling at Athena. But in

their possible defense, regarding the MELAS panel, it may be that there are an

array of tests of decreasing frequency of mutation occurrence, and that doctors

reasonably differ as to testing methodology.

Several sites identified the most likely two as 3243 around 80%, and 3271 as

about 7.5%, and in fact these two head off the Athena list. One doctor might

want to test just the first of those, before ordering the second only if the

first is negative. But another doctor might do both at once. It looks to me that

there might be disagreement about some of the much less common mutations, as to

how to count them (MELAS or something else) and how often to even test for them.

But I would imagine that Athena's choice is responsible by SOME rationale

(possibly just profit motivated), and I would certainly expect that they do

generally give accurate results for each test properly performed (let's hope

they occasionally run blind checks). Whether the blood tested is actually from

the right patient, or is contaminated by poor handling, or poorly stored so as

to negate all results, is another story.

I think Athena's list is perhaps more inclusive than most panels in common

usage. Note for instance that I could find only occasional oblique reference to

13513 in a MELAS search, but it is in the title of an article below, as a MELAS

mutation. Also for example 3256 is listed below, from neuro.wustl.edu, as being

" MERRF-like " . Another example, 3252 is listed as " ENCEPHALOMYOPATHY,

MITOCHONDRIAL " (a rather general term) at OMIM.

The long OMIM article on MTTL1 at http://www.fonama.org/i_omim/590050.html has a

major line item for most of the " Athena list " , but describes some without the

term " MELAS " , which might be part of the confusion. Perhaps the better title for

the Athena panel should be " MELAS+ " .

Steve D.

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From http://www.emedicine.com/ped/topic1406.htm

MELAS has been associated with at least 6 different point mutations, 4 of which

are located in the same gene, the tRNALeu (UUR) gene in MELAS. The most common

mutation, found in 80% of individuals with MELAS, is an A-to-G transition at

nucleotide (nt)-3243 in the tRNALeu (UUR) gene. An additional 7.5% have a

heteroplasmic T-to-C point mutation at base pair (bp) 3271 in the terminal

nucleotide pair of the anticodon stem of the tRNALeu (UUR) gene.

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From http://www.neuro.wustl.edu/neuromuscular/mitosyn.html#melas

Screen for most common mutations associated with syndrome

e.g. MELAS A3243G then T3271C

mtDNA point mutations

a.. Heteroplasmic: Mutant mtDNA proportion ~ 56% to 95%

b.. Genes

a.. tRNA Leu (common)

a.. A3243G mutation: 80% of MELAS syndromes

b.. Other MELAS mutation loci: T3271C has later age of onset; 3291

c.. Other syndromes with tRNA Leu mutations

a.. Riboflavin sensitive myopathy (T3250C)

b.. Isolated cardiomyopathy (A3243G; A3260G)

c.. Diabetes (A3243G; C3256T)

d.. Sudden infant death (SIDS)

e.. MERRF-like with diabetes, optic neuropathy & retinopathy (C3256T)

f.. Fatigue

g.. Rhabdomyolysis (A3243G)

b.. tRNA Leu 2 (MTTL2; CUN) : Also cardiomyopathy, PEO, sideroblastic anemia

c.. Cytochrome c Oxidase (Subunit 3 of Complex IV) : COX reduced; Few SDH +

fibers

d.. tRNA Val (G1642A) : Also Leigh syndrome

e.. tRNA Ser : MERRF/MELAS overlap

f.. tRNA Phe (G583A) : Also myoglobinuria

g.. tRNA Lys (T8316C) : MERRF with other mutations

h.. tRNA His (T12417G)

i.. tRNA Gln (A4332G) : Atypical MELAS syndrome with deafness

j.. NADH-Dehydrogenase Subunit 1 (MTND1) : MELAS, LHON or overlap phenotype

k.. MTND5 (Complex I): MELAS + Leigh syndromes

l.. MTND6 (Complex I): LHON is most common phenotype; Occasional early

onset MELAS or Leigh with Complex I deficiency

m.. Cytochrome b (Complex III): Myopathy is most common phenotype;

Occasional MELAS

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From http://jmg.bmjjournals.com/cgi/content/full/40/3/188

Article Title: The mitochondrial DNA G13513A MELAS mutation in the NADH

dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated

complex I deficiency

lots of melas ?

it seems as though an awful lot of people (adults with mito) at least

from this list have melas ! can anyone hazard a guess as to % ?

----- Original Message -----