Badania genetyczne

Badania genetyczne są istotnym elementem diagnozy choroby. Badania te potwierdzają występowanie konkretnego schorzenia. Również i ja poddałam się takim badaniom.
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Pani Blance Borkowskie - Sagan dziękuję bardzo serdecznie za przetłumaczenie wyników badań na język angielski.
Oto ich treść:
The study follows molecular diagnostics of ALPL gene.
The last diagnostic stage analyzed selected fragments of coding sequences of the gene and it identified it's mutation p.Glu311Lys in one allele (test results MedGen dated 15 January 2017). This mutation is registered in HGMD database for ALPL gene; however, according to the information from the abovementioned data base, the mutation was described in medical literature only once (a child with skeletal dysplasia and hypophosphatasia recognized in scan tests, the patient was identified with two ALPL gene mutations in total). Therefore, the analysis of detected mutation was performed with the use of Alamut software. The bioinformatic analysis showed that, both G nucleotide at position 931 of mRNA chain and amino acid Glu at position 311 of peptide chain are strongly evolutionary  conserved. Physicochemical differences between Glu and Lys are slight (56 Grantham score, range from 0 to 215). SIFT and Polyphen software, indicate that the conversion of Glu at position 311 of peptide chain into Lys is potentially pathogenic. In conclusion, the available data show that the identified alteration has a high probability of being pathogenic.

Currently, the study is extended to analysis of another fragments of ALPL gene coding sequences (exon 11).
No mutation was found in any of the alleles in currently tested ALPL gene regions.
It is recommended to perform the analysis of the carrier of the identified mutation in patient's parents and relatives, in order to establish the origin of the mutation. For people with detected mutation, clinical verification is needed to identify possible symptoms of mild hypophosphatasia.
It is also recommended to expand the analysis of APPL gene for the patient by testing further coding fragments, in order to identify the second potential mutation. (current tests)
On the assumption of pathogenic nature of the identified mutation, it should be noted that the patient has higher risk of having a child suffering from hypophosphatasia. On that account, in future it is suggested to perform genetic consultation and mutation carrier state testing on ALPL gene for the patient's partner.

Genetic advise is recommended.

Selected fragments of coding sequences of the ALPL gene (exon 11) were analyzed, using DNA sequencing technique.

Current examination result is an extension to molecular diagnostics of ALPL gene.In the first stage of molecular diagnostics, the p.Glu311Lys mutation was detected in one allele of the examined gene (test results CM MedGen dated 15 January 2017).
Presently, the diagnostic tests were extended and the mutation p.Arg272His was detected in one allele of the examined gene. This mutation is registered in HGMD database as mutation associated with hypophosphatasia.
On the assumption that mutations were detected in two, independent copies of ALPL gene, the attained result poses molecular confirmation of clinical diagnosis of hypophosphatasia.
The current result forms the basis for carriers testing of detected abnormalities in patient's relatives.
In case of reproductive planning, the patient's partner should be considered to be tested on ALPL gene.
Genetic advise is recommended to discuss the results of examination.

Selected fragments of coding sequences of the ALPL gene (exons: 2,3,4,7,8) were analyzed, using DNA sequencing technique.
Hypophosphatasia is caused by ALPL gene mutations coding TNSALP (Tissue non-specific alkaline phosphatase). The degree of clinical severity of the disorder may vary. A severe perinatal and neonatal form of the disease is heritable in an autosomal recessive way. A milder form the disease, especially an adult or odonto  hypophosphatasia can be either autosomal dominant or recessive, depending on the effects of ALPL gene mutation regarding enzymatic activity TNSALP. In case of recessive inheritance, parents of the patient are obligatory carriers (heterozygotes) of the mutation. In parents, either biochemical abnormalities with no clinical abnormalities are diagnosed or there are mild clinical symptoms, depending on the type of ALPL gene mutation.