T9176G

# **General Information**

| **Position** | **9176** | **Variant** | **m.9176T\>G** | **Locus** | **MT\-ATP6** | **Amino\-AcidChange** | **L217R** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | Pathogenic | **Pathogenicity** | Cfrm \[LP] |

"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.9176T\>G** variant in MT\-ATP6 has been reported in 5 pedigrees. To date, 15 carriers have been reported. Homoplasmy was reported in 4/15 carriers (26\.7%), and 7/15 carriers (46\.7%) were affected. The main clinical manifestations among affected carriers included leigh syndrome, severe neurodegenerative disorder, developmental delay, 3\-hydroxyisovaleric, 3\-hydroxypropionic, high C3, spinocerebellar syndrome, and methylcitric aciduria, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 9176 | m.9176T\>G | T9176G\-F1 | Italy | Leigh syndrome; spinocerebellar syndrome | 13 | 2 | 2001 | [11245730](https://pubmed.ncbi.nlm.nih.gov/11245730/) |  |
| 2 | 9176 | m.9176T\>G | T9176G\-F2 | Japan | Leigh syndrome | 1 | 1 | 2002 | [11731285](https://pubmed.ncbi.nlm.nih.gov/11731285/) |  |
| 3 | 9176 | m.9176T\>G | T9176G\-F3 | Italy | Leigh syndrome | 0 | 0 | 2000 | [11382202](https://pubmed.ncbi.nlm.nih.gov/11382202/) |  |
| 4 | 9176 | m.9176T\>G | T9176G\-F4 | USA | ATP6/8 deficiency; multiple\-carboxylase\-deficiency\-like biochemical phenotype | 0 | 0 | 2018 | [29307858](https://pubmed.ncbi.nlm.nih.gov/29307858/) |  |
| 5 | 9176 | m.9176T\>G | T9176G\-F5 | USA | ATP6/8 deficiency; multiple\-carboxylase\-deficiency\-like biochemical phenotype | 0 | 0 | 2018 | [29307858](https://pubmed.ncbi.nlm.nih.gov/29307858/) |  |

# **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 | 9176 | m.9176T\>G | T9176G\-F1 | T9176G\-F1\-IV1 | Fam | F | Y | Y | A | 10 | \>\=95% | \>\=95% | / | \>\=95%(F) | Severe neurodegenerative disorder; seizures; drug\-resistant epilepsy; ataxia; spastic paraparesis |  |
| 2 | 9176 | m.9176T\>G | T9176G\-F1 | T9176G\-F1\-IV2 | Fam | F | N | Y | D | ND | / | / | / | \>\=95%(postmortem tissues) | Leigh syndrome; severe neurodegenerative disorder |  |
| 3 | 9176 | m.9176T\>G | T9176G\-F1 | T9176G\-F1\-III9 | Fam | M | N | Y | A | ND | 70% | / | / | / | Spinocerebellar syndrome |  |
| 4 | 9176 | m.9176T\>G | T9176G\-F1 | T9176G\-F1\-III10 | Fam | F | N | N | A | ND | 50% | / | / | / | Healthy |  |
| 5 | 9176 | m.9176T\>G | T9176G\-F1 | T9176G\-F1\-II1 | Fam | F | N | N | A | ND | 8% | / | / | / | Healthy |  |
| 6 | 9176 | m.9176T\>G | T9176G\-F1 | T9176G\-F1\-II2 | Fam | F | N | N | A | ND | 30% | / | / | / | Healthy |  |
| 7 | 9176 | m.9176T\>G | T9176G\-F1 | T9176G\-F1\-III6 | Fam | M | N | N | A | ND | 43% | / | / | / | Healthy |  |
| 8 | 9176 | m.9176T\>G | T9176G\-F1 | T9176G\-F1\-III7 | Fam | M | N | N | A | ND | 28% | / | / | / | Healthy |  |
| 9 | 9176 | m.9176T\>G | T9176G\-F1 | T9176G\-F1\-III8 | Fam | M | N | N | A | ND | 39% | / | / | / | Healthy |  |
| 10 | 9176 | m.9176T\>G | T9176G\-F2 | T9176G\-F2\-II1 | Fam | F | Y | Y | D | 6y1mo | / | Homo | / | Homo(F) | Leigh syndrome; developmental delay; convulsions; unable to walk |  |
| 11 | 9176 | m.9176T\>G | T9176G\-F2 | T9176G\-F2\-II2 | Fam | M | N | Y | D | 10y7mo | / | Homo | / | / | Leigh syndrome; developmental delay; muscle hypotonia |  |
| 12 | 9176 | m.9176T\>G | T9176G\-F2 | T9176G\-F2\-I2 | Uninf | F | N | N | A | ND | \~50% | / | / | / | Healthy |  |
| 13 | 9176 | m.9176T\>G | T9176G\-F3 | T9176G\-F3\-P1 | Fam | ND | Y | Y | A | 10 | / | / | / | 100%(F) | Leigh syndrome; epilepsy; ataxic\-spastic gait; dystonia; axonal sensorimotor polyneuropathy; cerebellar and basal ganglia lesions. |  |
| 14 | 9176 | m.9176T\>G | T9176G\-F4 | T9176G\-F4\-P1 | De novo | F | Y | Y | D | 12 mo | Homo | / | / | / | High C3, high C5OH, low citrulline; lactic, 3\-hydroxyisovaleric, 3\-hydroxypropionic, and methylcitric aciduria; poor neonatal feeding and failure to thrive; died at 12 months after neurologic symptoms during acute diarrheal illness. | Mother tested negative for proband's mtDNA mutation. |
| 15 | 9176 | m.9176T\>G | T9176G\-F5 | T9176G\-F5\-P1 | Uninf | F | Y | N | A | 15 mo | Homo | / | / | / | High C5OH; elevated succinic acid; mildly elevated lactate and alanine; normal carboxylase activity; normal growth and age\-appropriate milestones at 15 months. |  |

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