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. 2012 Nov;35(6):1059-69.
doi: 10.1007/s10545-012-9465-2. Epub 2012 Mar 9.

Clinical features and heteroplasmy in blood, urine and saliva in 34 Dutch families carrying the m.3243A > G mutation

Paul de Laat  1 , Saskia Koene, Lambert P W J van den Heuvel, Richard J T Rodenburg, Mirian C H Janssen, Jan A M Smeitink
Affiliations

Clinical features and heteroplasmy in blood, urine and saliva in 34 Dutch families carrying the m.3243A > G mutation

Paul de Laat et al. J Inherit Metab Dis. 2012 Nov.

Erratum in

  • J Inherit Metab Dis. 2012 Nov;35(6):1155-6

Abstract

The m.3243A>G mutation has become known as the MELAS mutation. However, many other clinical phenotypes associated with this mutation have been described,most frequently being Maternally Inherited Diabetes and Deafness (MIDD). The m.3243A>G mutation, can be detected in virtually all tissues, however heteroplasmy differs between samples. Recent reports indicate, a preference to perform mutation analysis in Urinary Epithelial Cells(UEC). To test this, and to study a correlation between the mutational load in different tissues with two mitochondrial scoring systems (NMDAS and NPMDS) we investigated 34 families carrying the m.3243A>G mutation. Heteroplasmy was determined in three non-invasively collected samples,namely leucocytes, UEC and buccal mucosa. We included 127 patients, of which 82 carried the m.3243A>G mutation.None of the children (n011) had specific complaints. In adults(n071), a median NMDAS score of 15 (IQR 10-24) was found. The most prevalent symptoms were hearing loss(68 %), gastro-intestinal problems (59 %), exercise intolerance(54 %) and glucose intolerance (52 %). Ten patients had neurologic involvement. Buccal mucosa had the best correlation with the NMDAS in all adults (r00.437, p<0.001),whereas UEC had the strongest correlation with the NMDAS in severely affected patients (r00.593, p00.002). Heteroplasmy declined significantly with increasing age in all three samples (leucocytes r0-0.705 (p<0.001), UEC r0-0.374 (p00.001), buccal mucosa r0-0.460 (p<0.001). In our cohort of 82 patients, the m.3243A>Gmutation causes a wide variety of signs and symptoms, MIDD being far more prevalent than MELAS. Looking at the characteristics of the three noninvasively available tissues for testing heteroplasmy we confirm that UEC are the preferred sample to test [corrected].

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Figures

Fig. 1
Fig. 1
a-c: All clinical features scored by the NMDAS. Results of the Newcastle Mitochondrial Disease Adult Scale (NMDAS) are shown divided in the three sections of the scale, for all adult carriers of the m.3243A > G mutaion (n = 71). a) Section 1: Current function; b) Section 2: System-specific involvement; C) Section 3: Current clinical assessment
Fig. 2
Fig. 2
Quality of life Section 4 of the NMDAS is a QoL test, divided in QoLP and QoLM. All adult carriers of the m.3243A > G mutation are shown (n = 71). The line at 50 shows the US average of the test. QoLP is significantly lower than the US average
Fig. 3
Fig. 3
a-c: Heteroplasmy levels in all patients carrying the m.3243A > G mutation (n = 82) in three different samples (leucocytes, UEC and buccal mucosa) are correlated
Fig. 4
Fig. 4
a-c: Heteroplasmy vs age heteroplasmy levels in all patients carrying the m.3243A > G mutation (n = 82) show a negative correlation to age in leucocytes, UEC and buccal saliva
Fig. 5
Fig. 5
a-c: Heteroplasmy vs NMDAS score Heteroplasmy levels in leucocytes, UEC and buccal saliva in all adult patients carrying the m.3243A > G mutation (n = 71) show a correlation to the score on the NMDAS
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