Mój przypadek Miopatii Mitochondrialnej nazywa się choroba POLG, poniżej na obrazku jest pokazane strzałkami gdzie mam uszkodzenia. Jak mówi badanie genetyczne wykonane w WUM.
„Badanie molekularne genu POLG ujawniło obecność trzech zmian: T251I, P587L, K1191N.

  • Dwie z nich : T251I (czerwone), K1191N (niebieskie) są opisywane w literaturze jako recesywne mutacje patogenne i mogą odpowiadać za chorobę pacjenta.
  • Charakter zmiany P587L (niebieskie) jest nieustalony.

Wynik: badanie ujawniło zmiany: T251I, P587L, K1191N w stanie heterozygotycznym„

Dokładne wyniki badań wykonanych w klinice Warszawskiego Uniwersytetu Medycznego znajdziesz w dokumentach.

miopatia mitochondrialna / choroba polg

Dla mutacji T251I możliwe:
Progresive External Opthalmoplegia (arPEO – recesywne formy dziedziczenia) – postępujące porażenie nerwu okoruchowego oka

Dla mutacji P587L, K1191N możliwe
Alpers, Myocerebrohepatopathy and other Infantile Hepatocerebral Syndromes with mtDNA deletion – Zespół Alpersa, Miocerebrohepatopatia i inne dziecięce zespoły wątrobowo-mózgowe z dominującą delecją mtDNA.

dziedziczenie choroby

Amino Acid SubstitutioncDNA positionDiseaseDetailsFrequencyReferenceLink to PubMed
T251I752 c→t (exon 3)PEOar PEO. Found as compound with R309L, or 2354G insertion, or G848S in PEO.1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. (Ferrari et al., 2005) PubMed
PEOFound in compound with R807P (Del Bo et al., 2003) PubMed
Infantile Hepatocerebral SyndromeFrequently found in cis with P587L and compound in trans with L304R, V1106I, and R227W .Not found in 250 control individuals (Horvath et al., 2006) PubMed
PEOFound as compound in trans w/ S1176L, G848S, G785X, V1106I, R309L and R227W and cis w/ P587L. Also, T251I/P587L was found as a homozygous mutation. (Lamantea and Zeviani, 2004) PubMed
PEO and mtDNA deletionsFound in compound w/P587L/ R807P in1 pt. and w/P587L/ H932Y in a 2nd pt. A 3rd pt. was found in compound w/P587L only. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions.31 mitochondrial myopathy patients without any family history for the disorder (Di Fonzo et al., 2003) PubMed
Infantile Hepatocerebral Syndrome36% of patients with sporadic PEO with multiple mtDNA deletions carry mutations in one of the three genes associated with familial arPEO or adPE. Twinkle gene in 7% and POLG1 gene in 25% of our Italian and British patients with sporadic PEO. Found as compound in trans w/ R227W. Also, found as compound in cis with P587L.7 out of 27patients w/sporadic PEO compared to 250 controls individuals. (Agostino et al., 2003) PubMed
MNGIEFound in cis with P587L and in trans w/N846S.Van Goethem, 2003: Not found in 280 control chromosomes ( Van Goethem et al., 2003c) PubMed
Infantile Hepatocerebral SyndromeFound in 1 of 9 infantile hepatocerebral syndrome patients. In cis with P587L and compound with R232G.9 infantile hepatocerebral patients of German and Italian descent. (Ferrari et al., 2005) PubMed
PEOPOLG molecular defects were found in 25% of patients with multiple mtDNA deletions and mitochondrial disease. Found in trans w/M603L and in cis with P587L.24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez – Vioque et al., 2006) PubMed
PEOFound in trans w/ G848S and in cis w/ P587L in a 75 y.o. male. (Kollberg et al., 2005) PubMed
AlpersFound in trans w/ G848S and in cis w/ P587L. Also found in cis w/P587L and in trans w/R853Q in myocerebralhepatopathy patient. Also found as a heterozygous mutation with ataxia, ptosis, and neuropathy. (Wong et al., 2008) PubMed
AlpersFound in cis w/ R232G and cis w/ P587L. (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed
PEOFound in cis w/ P587L, with both mutations on each allele. A 2nd pt. found to have P587L in trans and A467T in cis. (Stewart et al., 2009) PubMed
mtDNA depletionIn cis w/P587L and in trans w/ E1136K (Taanman et al., 2008) PubMed
Hepatocerebral MDSFound in cis with P587L and in trans with R232G (Spinazzola et al., 2009) PubMed
Restless leg syndrome, ptosis, diplopia, limb weakness, blurred visionFound in trans with P587L. (Aitken, et al., 2009) PubMed
PEOFound in trans with W748S andP587L (Tzoulis, et al., 2009) PubMed
PEO and mental retardationFound in cis w/P587L and in trans w/ R275X<0.5% in Dutch population (Blok and van den Bosch et al., 2009) PubMed
PEO, exercise intolerance, diabetes and a 2nd pt. w/ cataract and myopathyFound in cis w/P587L and in trans w/ A467T<0.5% in Dutch population (Blok and van den Bosch et al., 2009) PubMed
PtosisFound in cis w/P587L and in trans w/ G848S<0.5% in Dutch population (Blok and van den Bosch et al., 2009) PubMed
Epilepsy and mental retardationad, Found w/P587L<0.5% in Dutch population (Blok and van den Bosch et al., 2009) PubMed
Seizures, hypotonia, and developmental delayFound w/P587L (Burusnukul and de los Reyes, 2009) PubMed
Acute disseminated encephalomyelitisFound w/P587L, found in one 4 y.o. patient with autoimmune central nervous system disease (Harris et al., 2010) PubMed
SANDOFound sporadically w/P587L and G848S in a 80 y.o. male (Wiess and Saneto, 2010) PubMed
Ptosis and myopathyFound in cis with P587L and in trans with P648R in a 59 y.o. male with dysphagia, dysphonia, myopathy, ptosis, and mtDNA deletions. Father had same symptoms. (Ferreira et al., 2011) PubMed
PEOFound in cis w/ P587L and in trans w/ H932Y in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency.Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
Peripheral NeuropathyFound in cis w/ P587L and in trans w/ H932Y in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness.Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
PEOFound in cis w/ P587L and in trans w/ G848S in an 80 y.o. w/ peripheral neuropathy, ptosis, and abnormal muscle histologyFound in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
PEOFound in cis w/ P587L and in trans w/ K1191N in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weaknessFound in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
Found in cis w/ P587L and in trans w/ N1157S in a 9 y.o. Symptoms not notedFound in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
Found in trans w/ G588D and in cis w/ P587L in a 6 y.o. w/ no symptoms notedFound in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
PEOFound in compound with G848S in a 45 yo female with mtDNA deletionsFound in 160 French cohort of potential POLG patients (Rouzier et al., 2013) PubMed
P587L1760 c→t (exon 10)PEO, neuropathy, and hearing lossFound in trans w/ Q1236H in 2 different families and affected siblingsFilosto, 2003: not detected in 120 healthy control alleles. (Filosto et al., 2003) PubMed
PEO and mtDNA deletionsFound in compound w/T251I/ R807P in1 pt. and w/T251I/ H932Y in a 2nd pt. A 3rd pt. was found in compound w/T251 only. The study includes 31 mitochondrial myopathy patients w/ mtDNA deletions.Di Fonzo 2003: Not found in 100 DNA samples from healthy Italians. (Di Fonzo et al., 2003) PubMed
PEOFound in compound w/T251I and N864S in 2 sisters.Van Goethem, 2003: Not found in 280 control chromosomes. (Van Goethem et al., 2003c) PubMed
Infantile Hepatocerebral SyndromeFound in compound w/T251I and R232GFerrari et al., 2005 reported 1 in 9 (11.11%) children with a combination of progressive neurological and hepatic failure, with a heterozygous frequency of 1% of Italian controls. (Ferrari et al., 2005) PubMed
PEOFound in compound w/T251I and G8484S in a 75 y.o. male(Kollberg et al., 2005) PubMed
PEOFound as compound in trans w/ S1176L, G848S, G785X, V1106I, R309L and R227W and cis w/ T251I. Also, T251I/P587L was found as a homozygous mutation. (Lamantea and Zeviani, 2004) PubMed
PEOFound in cis w/T251I and trans w/M603L. Also found in trans w/ R853W (no T251I). All had mtDNA deletions.24 patients diagnosed with mitochondrial disease and having multiple mtDNA deletions compared to 100 controls in a Spanish population. (Gonzalez-Vioque et al., 2006) PubMed
AlpersFound in cis w/ T251I and in trans w/ G848S, also found as a hetero. mutation with ataxia, ptosis, and neuropathy (Wong et al., 2008) PubMed
AlpersFound in trans w/R232G and in cis w/T251I. Also, in cis w/P589L and in trans w/W748S. (Ashley et al., 2008) and a correction in (Ashley et al., 2009) PubMed
AlpersFound in cis with T251I with both mutations on each allele. Also, found in cis w/A467T and in trans w/T251I. (Stewart et al., 2009) PubMed
mtDNA depletionIn cis w/T251I and in trans w/E1136K (Taanman et al., 2008) PubMed
Hepatocerebral MDSFound in cis w/ T251I and in trans w/ R232G (Spinazzola et al., 2009) PubMed
Restless leg syndrome, ptosis, diplopia, limb weakness, blurred visionFound in trans with T251I. (Aitken, et al., 2009) PubMed
PEOFound in cis with W748S and in trans with T251I. (Tzoulis, et al., 2009) PubMed
PEO and mental retardationFound in cis w/ T251I and in trans w/ R275X>0.5% of Dutch population (Blok and van den Bosch et al., 2009) PubMed
PEO, exercise intolerance, diabetes and a 2nd pt. w/ cataract and myopathyFound in cis w/T251I and in trans w/A467T>0.5% of Dutch population (Blok and van den Bosch et al., 2009) PubMed
PtosisFound in cis w/T251I and in trans w/G848S>0.5% of Dutch population (Blok and van den Bosch et al., 2009) PubMed
PEO, ptosis, epilepsy, mental retardation, ataxia, polyneuropathy, and cataractAd, in cis w/T251I 3 patients: 4 yr. old w/PEO, ptosis, and motor delay development. A 10 yr. old with epilepsy and mental retardation, and 44 yr. old w/ cataract, polyneuropathy, myopathy, and ataxia>0.5% of Dutch population (Blok and van den Bosch et al., 2009) PubMed
Seizures, hypotonia, and developmental delayFound w/T251I (Burusnukul and de los Reyes, 2009) PubMed
Acute disseminated encephalomyelitisFound w/T251I, found in one 4 yr. old patient with autoimmune central nervous system disease (Harris et al., 2010) PubMed
SANDOFound sporadically w/T251I and G848S in a 80 yr. old male (Weiss and Saneto, 2010) PubMed
Ptosis and myopathyFound in cis with T251I and in trans with P648R in a 59 y.o. male with dysphagia, dysphonia, myopathy, ptosis, and mtDNA deletions. Father had same symptoms. (Ferreira et al., 2011) PubMed
PEOFound in cis w/ T251I and in trans w/ H932Y in a 31 y.o. w/ neuropathy, PEO, ptosis, and COX deficiency.Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
Peripheral NeuropathyFound in cis w/ T251I and in trans w/ H932Y in a 40 y.o. w/ peripheral neuropathy, ptosis, and muscle weakness.Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
PEOFound in cis w/ T251I and in trans w/ G848S in an 80 y.o. w/ peripheral neuropathy, ptosis, and abnormal muscle histology.Found in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
PEOFound in cis w/ T251I and in trans w/ K1191N in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weaknessFound in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
Found in cis w/ T251I and in trans w/ N1157S in a 9 y.o. Symptoms not notedFound in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
Found in trans w/ G588D and in cis w/ T251I in a 6 y.o. w/ no symptoms notedFound in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed
K1191N3573 g→t (exon 22)AlpersCompound in trans with A467TNot found in 250 control individuals (Horvath et al., 2006) PubMed
PEOFound in trans w/ T251I and P587L in a 39 y.o. w/ PEO, neuropathy, ptosis, and muscle weaknessFound in a cohort of 2697 patients with suggestive clinical presentations of POLG deficiencies. (Tang et al., 2011) PubMed

Źródło: National Institute of Environmental Health Sciences (NIEHS)