CMT disorders with autosomal recessive inheritance

[Guest guest]

Med Wieku Rozwoj. 2009;XIII(2):146-153.

Charcot-Marie-Tooth disorders with autosomal recessive inheritance. search for

the molecular diagnostics model.

Kabziñska D, Franaszczyk M, Kochañski A.

Zespó³ Chorób Nerwowo-Mieœniowych Instytutu Medycyny Doœwiadczalnej i Klinicznej

im. M.J. Mossakowskiego Polskiej Akademii Nauk, ul. A. Pawiñskiego 5, 02-106

Warszawa

The aim was focused on molecular analysis of the selected genes associated with

autosomal recessive Charcot-Marie-Tooth neuropathies (AR-CMT) and construction

of a molecular diagnostic algorithm in this group of disorders in the Polish

population.

MATERIAL AND METHODS: We analyzed a group of 138 subjects from 62 families with

probably autosomal recessive inheritance and the control group of 52

individuals. The studies covered molecular genetic analysis of PMP22 gene dosage

(real-time polymerase chain reaction and polymerase chain reaction restriction

fragments length polymorphisms), analysis of coding regions of the GDAP1, PRX,

EGR2 and CTDP1 genes using: mutation screening (single strand conformation

polymorphism and heteroduplex analysis), sequencing and bioinformatics approach

to the gene sequence variants.

RESULTS: Thirty sequence variants have been found in the analysed genes, 5

pathogenic mutations in the GDAP1 gene and 2 pathogenic mutations in the PRX

gene. On the basis of bioinformatic analysis other nucleotide changes have been

categorized as harmless polymorphisms and variants of unknown pathogenic effect.

CONCLUSIONS: This is the first study focused on the autosomal recessive

Charcot-Marie-Tooth disease in the Polish population. Our results show the

difficulties in the interpretation of the pathogenic effect of the sequence

variants (pathogenic mutation or polymorphism) which is essential for molecular

diagnostics in CMT disease.

[Guest guest]

Thank you for posting this. To the best of my ability I understand this to say

that of all the mutations found on the PRX gene that only 2 of those were

pathogenic (disease causing). Do they have those 2 mutations identified

anywhere? Or do we assume that if the Athena lab says " amino acid change of

unknown significance " that it is not one of the 2 known to be pathogenic.

Thanks for reading!

>

> Med Wieku Rozwoj. 2009;XIII(2):146-153.

>

> Charcot-Marie-Tooth disorders with autosomal recessive inheritance. search for

the molecular diagnostics model.

>

> Kabziñska D, Franaszczyk M, Kochañski A.

>

> Zespó³ Chorób Nerwowo-Mieœniowych Instytutu Medycyny Doœwiadczalnej i

Klinicznej im. M.J. Mossakowskiego Polskiej Akademii Nauk, ul. A. Pawiñskiego 5,

02-106 Warszawa

>

> The aim was focused on molecular analysis of the selected genes associated

with autosomal recessive Charcot-Marie-Tooth neuropathies (AR-CMT) and

construction of a molecular diagnostic algorithm in this group of disorders in

the Polish population.

>

> MATERIAL AND METHODS: We analyzed a group of 138 subjects from 62 families

with probably autosomal recessive inheritance and the control group of 52

individuals. The studies covered molecular genetic analysis of PMP22 gene dosage

(real-time polymerase chain reaction and polymerase chain reaction restriction

fragments length polymorphisms), analysis of coding regions of the GDAP1, PRX,

EGR2 and CTDP1 genes using: mutation screening (single strand conformation

polymorphism and heteroduplex analysis), sequencing and bioinformatics approach

to the gene sequence variants.

>

> RESULTS: Thirty sequence variants have been found in the analysed genes, 5

pathogenic mutations in the GDAP1 gene and 2 pathogenic mutations in the PRX

gene. On the basis of bioinformatic analysis other nucleotide changes have been

categorized as harmless polymorphisms and variants of unknown pathogenic effect.

>

> CONCLUSIONS: This is the first study focused on the autosomal recessive

Charcot-Marie-Tooth disease in the Polish population. Our results show the

difficulties in the interpretation of the pathogenic effect of the sequence

variants (pathogenic mutation or polymorphism) which is essential for molecular

diagnostics in CMT disease.

>