A13528G

# **General Information**

| **Position** | **13528** | **Variant** | **m.13528A\>G** | **Locus** | **MT\-ND5** | **Amino\-AcidChange** | **T398A** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \- | **APOGEE2** | Benign | **Pathogenicity** | Reported \[LB] |

"Pathogenicity" status is derived from published literature or predictions from bioinformatics tools. Researchers and clinicians are cautioned that additional data and/or analysis may still be necessary to confirm the pathological significance of these variants. For more information, please see [Mitofam Info](https://mitofam.com/doc/385/).

# **Pedigree Information**

The **m.13528A\>G** variant in MT\-ND5 has been reported in 7 pedigrees. To date, 22 carriers have been reported. Homoplasmy was reported in 9/22 carriers (40\.9%), and 14/22 carriers (63\.6%) were affected. The main clinical manifestations among affected carriers included autism spectrum disorder., diabetes, lHON\-like ocular symptoms, ataxia, lHON phenotype, leigh syndrome, MELAS, renal failure, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 13528 | m.13528A\>G | [A13528G\-F1 ](https://mitofam.com/doc/1318/)| France | LHON\-like ocular symptoms | 0 | 0 | 2000 | [11102991](https://pubmed.ncbi.nlm.nih.gov/11102991/) |  |
| 2 | 13528 | m.13528A\>G | [A13528G\-F2 ](https://mitofam.com/doc/1319/)| UK | MELAS | 1 | 0 | 2007 | [17940288](https://pubmed.ncbi.nlm.nih.gov/17940288/) | two target variants carried in same maternal line.; Patient 1 and mother; pages 1,3,4,7; UK mitochondrial disease centre / UCL affiliations |
| 3 | 13528 | m.13528A\>G | A13528G\-F3 | Sweden | Leigh syndrome | 0 | 0 | 2009 | [19103152](https://pubmed.ncbi.nlm.nih.gov/19103152/) | m.13528A\>G noted as not conserved/LHON\-like phenotype reference; not listed as pathogenic mtDNA mutation in Table 2\.; Patient 8; Tables 1\-3\.; Sweden; all patients born in central Sweden with some non\-Swedish parental origin. |
| 4 | 13528 | m.13528A\>G | [A13528G\-F4](https://mitofam.com/doc/1320/) | Italy | Leber hereditary optic neuropathy / optic subatrophy | 8 | 1 | 2012 | [22589247](https://pubmed.ncbi.nlm.nih.gov/22589247/) | Authors conclude apparent heteroplasmy was explained by NumtS interference; variant may represent haplogroup U4b1b polymorphism.; Fig.1 family; Clinical pedigree and PCR\-RFLP/deep\-sequencing analyses of proband, mother, and sister.; Italy; Italian family and clinical workup reported by Italian centers |
| 5 | 13528 | m.13528A\>G | [A13528G\-F5](https://mitofam.com/doc/1321/) | United Kingdom | MELAS\-like mitochondrial disease with POLG A467T background | 1 | 0 | 2016 | [26735972](https://pubmed.ncbi.nlm.nih.gov/26735972/) | POLG homozygous A467T is major nuclear background; mtDNA variants should be annotated cautiously.; Patient 4 family; Patient table and genetic discussion.; United Kingdom/European clinical genetics setting; Same Patient 4 report lists C13565T, but mother evidence was not extrapolated to C13565T. |
| 6 | 13528 | m.13528A\>G |[ A13528G\-F6](https://mitofam.com/doc/1322/) | USA inferred | autism spectrum disorder | 0 | 3 | 2017 | [28419775](https://pubmed.ncbi.nlm.nih.gov/28419775/) | Use cautiously: individual labels/genders/ages/load absent; only aggregate family\-level affected sibling evidence is available.; ASD family 74\-0733; pages 1\-4; USA inferred from ASD cohort/source and affiliations. |
| 7 | 13528 | m.13528A\>G | A13528G\-F7 | France | LHON\-like ocular symptoms | 0 | 0 | 2000 | [11102991](https://pubmed.ncbi.nlm.nih.gov/11102991/) |  |

# **Carrier Information**

| **No.** | **Position** | **Variant** | **Family ID** | **Carrier ID** | **Type (Fam/De novo/Uninf)** | **Gender (F/M)** | **Proband (Y/N)** | **Affected (Y/N)** | **Die/Alive(D/A)** | **Age** | **Blood Mutant Level** | **Muscle Mutant level** | **Urine Mutant level** | **Other Mutant level** | **Clinical Features** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 13528 | m.13528A\>G | A13528G\-F1 | A13528G\-F1\-II1 | Fam | F | Y | Y | ND | ND | Homo | / | / | / | LHON\-like ocular symptoms |  |
| 2 | 13528 | m.13528A\>G | A13528G\-F1 | A13528G\-F1\-I1 | Uninf | F | N | ND | ND | ND | Homo | / | / | / | ND |  |
| 3 | 13528 | m.13528A\>G | A13528G\-F7 | A13528G\-F7\-P1 | Uninf | ND | Y | Y | ND | ND | Homo | / | / | / | LHON\-like ocular symptoms | Patient 2 |
| 4 | 13528 | m.13528A\>G | A13528G\-F2 | A13528G\-F2\-II1 | Fam | F | Y | Y | ND | ND | m.13528A\>G 99\.9%; m.13565C\>T Homo | m.13528A\>G Homo; m.13565C\>T Homo | / | Homo(F) | MELAS; neuropathy; hearing impairment | patient muscle homoplasmic for both; blood near homoplasmic for m.13528; results/discussion; Source: Patient 1; Daughter/proband; same report also supports separate C13565T family.; COX\-negative ragged\-red fibers. |
| 5 | 13528 | m.13528A\>G | A13528G\-F2 | A13528G\-F2\-I2 | Fam | F | N | N | ND | 65 | m.13528A\>G approx 93\.9%; m.13565C\>T Homo | / | / | / | Healthy | 6\.1% wild type at m.13528 in blood; discussion; Source: mother |
| 6 | 13528 | m.13528A\>G | A13528G\-F3 | A13528G\-F3\-P1 | Uninf | F | Y | Y | A | 22 y at report; onset birth | / | / | / | / | Leigh syndrome; hypotonia, developmental retardation, epilepsy, poor feeding, ataxia/dystonia features in Table 1 | Variant listed in Table 3 as m.13528A\>G in patient 8; mutation load not quantified and pathogenicity uncertain.; Tables 1\-3 and discussion.; Source: Patient 8 |
| 7 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-II2 | Uninf | M | Y | Y | A | 50 | Homo | / | / | Homo(F) | LHON phenotype; optic subatrophy; visual impairment | Tested in blood and fibroblasts; apparent heteroplasmy explained by NumtS in the paper.; Fig.1 and PCR\-RFLP/deep sequencing text.; Source: II\-2 |
| 8 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-I2 | Uninf | F | N | N | A | ND | Homo | / | / | / | Healthy | Mother of proband; clinically healthy carrier.; Pedigree and PCR\-RFLP text.; Source: I\-2; No visual impairment reported. |
| 9 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-II7 | Uninf | F | N | N | A | ND | Homo | / | / | / | Healthy | Sister of proband; clinically healthy carrier.; Pedigree and PCR\-RFLP text.; Source: II\-7; No visual impairment reported. |
| 10 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-II1 | Fam | M | N | N | A | 48 | / | / | / | / | Healthy | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 11 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-II3 | Fam | F | N | Y | A | 52 | / | / | / | / | Diabetes | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported.; No visual impairment reported in pedigree. |
| 12 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-II4 | Fam | M | N | N | A | 56 | / | / | / | / | Healthy | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 13 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-II5 | Fam | F | N | Y | A | 58 | / | / | / | / | Diabetes | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported.; No visual impairment reported in pedigree. |
| 14 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-II6 | Fam | M | N | N | A | 60 | / | / | / | / | Healthy | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 15 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-II8 | Fam | M | N | Y | A | 65 | / | / | / | / | Diabetes | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported.; No visual impairment reported in pedigree. |
| 16 | 13528 | m.13528A\>G | A13528G\-F4 | A13528G\-F4\-II9 | Fam | F | N | Y | D | 13 | / | / | / | / | Renal failure; died at 13 years. | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 17 | 13528 | m.13528A\>G | A13528G\-F5 | A13528G\-F5\-II1 | Uninf | F | Y | Y | A | 31 | Homo | Homo | / | / | Seizures; stroke\-like episode; deafness; myopathic weakness; ptosis; ophthalmoparesis; dysarthria; ataxia | Patient 4; onset at 24; alive at 31 |
| 18 | 13528 | m.13528A\>G | A13528G\-F5 | A13528G\-F5\-I2 | Uninf | F | N | N | A | ND | Het | / | / | / | Healthy |  |
| 19 | 13528 | m.13528A\>G | A13528G\-F6 | A13528G\-F6\-II1 | Fam | ND | N | Y | A | ND | / | / | / | Positive(LCL) | Autism spectrum disorder. | Anonymous carrier; family also has m.13565C\>T.; pages 1\-4; Source: affected sibling 1 |
| 20 | 13528 | m.13528A\>G | A13528G\-F6 | A13528G\-F6\-II3 | Fam | ND | N | Y | A | ND | / | / | / | Positive(LCL) | Autism spectrum disorder. | Anonymous carrier; family also has m.13565C\>T.; pages 1\-4; Source: affected sibling 2 |
| 21 | 13528 | m.13528A\>G | A13528G\-F6 | A13528G\-F6\-II4 | Fam | ND | N | Y | A | ND | / | / | / | Positive(LCL) | Autism spectrum disorder. | Anonymous carrier; family also has m.13565C\>T.; pages 1\-4; Source: affected sibling 3 |
| 22 | 13528 | m.13528A\>G | A13528G\-F6 | A13528G\-F6\-II5 | Fam | ND | N | Y | A | ND | / | / | / | Positive(LCL) | Autism spectrum disorder. | Anonymous carrier; family also has m.13565C\>T.; pages 1\-4; Source: affected sibling 4 |

For abbreviations and other usage instructions, please see [Mitofam Info](https://mitofam.com/doc/385/).