T3271C

# **General Information**

| **Position** | **3271** | **Variant** | **m.3271T\>C** | **Locus** | **MT\-TL1** | **RNA** | **tRNA Leu (UUR)** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | Pathogenic | **Pathogenicity** | Cfrm \[P] |

"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.3271T\>C** variant in MT\-TL1 has been reported in 10 pedigrees. To date, 57 carriers have been reported. Reported mutation loads ranged from 0% to 98%, with a median of 57% overall; affected carriers showed mutation loads from 0% to 98%, with a median of 60%; unaffected carriers showed mutation loads from 4% to 88%, with a median of 27\.5%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in urine (35%) than in blood (less than 5%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in urine (43%) than in blood (less than 5%). Similar tissue\-specific differences were observed in 8 additional carriers. The main clinical manifestations among affected carriers included migraine, MELAS, short stature, muscle weakness, diabetes, distal amyotrophy, distal sensory loss, dysarthria, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3271 | m.3271T\>C |[ T3271C\-F1](https://mitofam.com/doc/2303/) | Japan | Diabetes | 1 | 2 | 1997 | [9455930](https://pubmed.ncbi.nlm.nih.gov/9455930/) |  |
| 2 | 3271 | m.3271T\>C | [T3271C\-F2](https://mitofam.com/doc/2304/) | Japan | Encephalo\-myo\-neuropathy | 4 | 3 | 2001 | [11404119](https://pubmed.ncbi.nlm.nih.gov/11404119/) |  |
| 3 | 3271 | m.3271T\>C | [T3271C\-F3](https://mitofam.com/doc/2305/) | USA | MELAS | 10 | 15 | 2005 | [15794182](https://pubmed.ncbi.nlm.nih.gov/15794182/) |  |
| 4 | 3271 | m.3271T\>C | [T3271C\-F4](https://mitofam.com/doc/2306/) | USA | MELAS | 2 | 4 | 2005 | [15794182](https://pubmed.ncbi.nlm.nih.gov/15794182/) |  |
| 5 | 3271 | m.3271T\>C | [T3271C\-F5 ](https://mitofam.com/doc/2307/)| Finland | MELAS | 4 | 0 | 2005 | [16006433](https://pubmed.ncbi.nlm.nih.gov/16006433/) |  |
| 6 | 3271 | m.3271T\>C | [T3271C\-F6](https://mitofam.com/doc/2308/) | France | MELAS | 1 | 0 | 2013 | [24153443](https://pubmed.ncbi.nlm.nih.gov/24153443/) | Carrying T9185C |
| 7 | 3271 | m.3271T\>C |[ T3271C\-F7 ](https://mitofam.com/doc/2309/)| Italy | MELAS | 1 | 0 | 2015 | [25680467](https://pubmed.ncbi.nlm.nih.gov/25680467/) |  |
| 8 | 3271 | m.3271T\>C | T3271C\-F8 | Japan | MELAS | ND | ND | 1993 | [7684581](https://pubmed.ncbi.nlm.nih.gov/7684581/) |  |
| 9 | 3271 | m.3271T\>C | T3271C\-F9 | Japan | MELAS | ND | ND | 1998 | [9766710](https://pubmed.ncbi.nlm.nih.gov/9766710/) |  |
| 10 | 3271 | m.3271T\>C | T3271C\-F10 | Japan | MELAS | ND | ND | 2003 | [12609508](https://pubmed.ncbi.nlm.nih.gov/12609508/) |  |

# **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 | 3271 | m.3271T\>C | T3271C\-F1 | T3271C\-F1\-I2 | Uninf | F | N | Y | A | ND | / | / | / | / | Diabetes |  |
| 2 | 3271 | m.3271T\>C | T3271C\-F1 | T3271C\-F1\-II2 | Fam | F | N | Y | A | ND | / | / | / | / | Diabetes |  |
| 3 | 3271 | m.3271T\>C | T3271C\-F1 | T3271C\-F1\-III1 | Fam | M | Y | Y | A | 39 | / | / | / | / | Diabetes |  |
| 4 | 3271 | m.3271T\>C | T3271C\-F1 | T3271C\-F1\-III2 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 5 | 3271 | m.3271T\>C | T3271C\-F2 | T3271C\-F2\-I2 | Uninf | F | N | N | D | 67 | / | / | / | / | Healthy |  |
| 6 | 3271 | m.3271T\>C | T3271C\-F2 | T3271C\-F2\-II1 | Fam | M | N | Y | D | 32 | / | / | / | / | Cerebellar ataxia, stroke, sudden death |  |
| 7 | 3271 | m.3271T\>C | T3271C\-F2 | T3271C\-F2\-II3 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 8 | 3271 | m.3271T\>C | T3271C\-F2 | T3271C\-F2\-II5 | Fam | F | Y | Y | A | 48 | / | / | / | / | Dementia (memory loss), photo\-reactive syncope/seizure, abnormal eye movement, hearing disturbance, dysarthria, facial myokymia \& spasm, tremor \& myoclonus, limb \& truncal ataxia, hypotonia, hyporeflexia, distal amyotrophy, distal sensory loss |  |
| 9 | 3271 | m.3271T\>C | T3271C\-F2 | T3271C\-F2\-III5 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 10 | 3271 | m.3271T\>C | T3271C\-F2 | T3271C\-F2\-III6 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 11 | 3271 | m.3271T\>C | T3271C\-F2 | T3271C\-F2\-III7 | Fam | M | N | Y | A | 20 | / | / | / | / | Photo\-reactive syncope/seizure, abnormal eye movement, hearing disturbance, dysarthria, facial myokymia \& spasm, tremor \& myoclonus, limb \& truncal ataxia, hypotonia, hyporeflexia, distal amyotrophy, distal sensory loss |  |
| 12 | 3271 | m.3271T\>C | T3271C\-F2 | T3271C\-F2\-III8 | Fam | M | N | Y | A | 19 | / | / | / | / | Photo\-reactive syncope/seizure, dysarthria, tremor \& myoclonus, limb \& truncal ataxia, hypotonia, hyporeflexia, distal amyotrophy, distal sensory loss |  |
| 13 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-I2 | Uninf | F | N | Y | A | ND | / | / | / | / | Stroke |  |
| 14 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-II1 | Fam | F | N | Y | A | ND | \<5% | / | 35% | / | Migraine |  |
| 15 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-II2 | Fam | F | N | Y | A | ND | / | / | / | / | Migraine,stroke |  |
| 16 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-II3 | Fam | F | N | Y | A | ND | \<5% | / | 43% | / | Migraine, hyperthyroidism |  |
| 17 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-II4 | Fam | F | N | Y | A | ND | / | / | / | / | Migraine |  |
| 18 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-II5 | Fam | F | N | Y | A | ND | / | / | / | / | Migraine |  |
| 19 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-III1 | Fam | F | N | Y | A | ND | \<5% | / | 58% | / | Migraine, short stature |  |
| 20 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-III2 | Fam | F | N | Y | A | ND | \<5% | / | 67% | / | Migraine, fatigue, muscle weakness |  |
| 21 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-III3 | Fam | F | N | Y | A | ND | / | / | 57% | / | Migraine |  |
| 22 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-III4 | Fam | M | Y | Y | D | 14 | / | / | / | / | Migraine, seizures, strokes, deafness, cortical blindness |  |
| 23 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-III5 | Fam | M | N | Y | A | ND | \<5% | / | 9% | / | Migraine |  |
| 24 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-III6 | Fam | F | N | Y | A | ND | 26% | / | 71% | / | Migraine, muscle weakness, supraventricular tachycardia |  |
| 25 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-III8 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 26 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-III9 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 27 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-III10 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 28 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV1 | Fam | M | N | Y | A | ND | 29% | / | 98% | / | Migraine, short stature, deafness, muscle weakness, chronic vomiting |  |
| 29 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV2 | Fam | M | N | N | A | ND | / | / | / | / | Short stature |  |
| 30 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV3 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 31 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV4 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 32 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV5 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 33 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV6 | Fam | M | N | Y | A | ND | / | / | 67% | / | Headaches, short stature, muscle cramps |  |
| 34 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV7 | Fam | M | N | Y | A | ND | / | / | 71% | / | Headaches, attention\-deficit hyperactivity disorder |  |
| 35 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV8 | Fam | M | N | Y | A | ND | / | / | \<5% | / | Muscle cramps |  |
| 36 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV9 | Fam | M | N | Y | A | ND | / | / | 32% | / | MELAS |  |
| 37 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV10 | Fam | M | N | Y | A | \<5 | / | / | 45% | / | MELAS |  |
| 38 | 3271 | m.3271T\>C | T3271C\-F3 | T3271C\-F3\-IV11 | Fam | F | N | Y | A | \<5 | / | / | 98% | / | MELAS |  |
| 39 | 3271 | m.3271T\>C | T3271C\-F4 | T3271C\-F4\-I1 | Uninf | F | N | Y | A | ND | / | / | / | / | Diabetes mellitus |  |
| 40 | 3271 | m.3271T\>C | T3271C\-F4 | T3271C\-F4\-II2 | Fam | F | N | Y | A | ND | 0 | / | 0 | 5% (BM), 65% (H) | Gestational diabetes mellitus, depression, seizures |  |
| 41 | 3271 | m.3271T\>C | T3271C\-F4 | T3271C\-F4\-II3 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 42 | 3271 | m.3271T\>C | T3271C\-F4 | T3271C\-F4\-II4 | Fam | M | N | Y | D | 12 | / | / | / | / | Mental retardation, cerebral palsy |  |
| 43 | 3271 | m.3271T\>C | T3271C\-F4 | T3271C\-F4\-II5 | Fam | F | N | Y | D | ND | / | / | / | / | MELAS |  |
| 44 | 3271 | m.3271T\>C | T3271C\-F4 | T3271C\-F4\-III6 | Fam | M | N | N | A | ND | 10% | / | 28% | 47% (BM), 88% (H) | Healthy |  |
| 45 | 3271 | m.3271T\>C | T3271C\-F4 | T3271C\-F4\-III7 | Fam | F | Y | Y | A | 7 | 31% | / | 60% | 82% (BM), 60% (H) | Migraine, short stature, seizures, psychomotor retardation, cortical blindness |  |
| 46 | 3271 | m.3271T\>C | T3271C\-F5 | T3271C\-F5\-III2 | Uninf | F | N | N | D | 42 | / | / | / | / | Healthy |  |
| 47 | 3271 | m.3271T\>C | T3271C\-F5 | T3271C\-F5\-IV2 | Fam | F | N | N | A | ND | 5% | / | / | / | Healthy |  |
| 48 | 3271 | m.3271T\>C | T3271C\-F5 | T3271C\-F5\-V1 | Fam | F | Y | Y | D | 6 | / | 94% | / | 94% (F), 85% (Brain), 92% (Heart), 89% (Liver) | poor growth, weight loss, exercise\-induced fatigue, exercise\-induced palpitation, ankle swelling, muscle atrophy, Achilles tendon tightness, excessive fatigue, vomiting, metabolic acidosis, bilateral pleural effusions, pneumothorax, anuria, decreased gastric motility, elbow and ankle contractions, partial growth hormone deficiency, therapy\-resistant partial seizures, stroke\-like lesions, multiorgan failure |  |
| 49 | 3271 | m.3271T\>C | T3271C\-F5 | T3271C\-F5\-V2 | Fam | F | N | N | A | 18 | 27% | / | / | / | Healthy |  |
| 50 | 3271 | m.3271T\>C | T3271C\-F5 | T3271C\-F5\-V3 | Fam | F | N | N | A | ND | 4% | / | / | / | Healthy |  |
| 51 | 3271 | m.3271T\>C | T3271C\-F6 | T3271C\-F6\-I2 | Uninf | F | N | N | A | 18 | / | / | / | / | Pes cavus, proprioceptive ataxia, pyramidal syndrome | Carrying T9185C |
| 52 | 3271 | m.3271T\>C | T3271C\-F6 | T3271C\-F6\-II1 | Fam | F | Y | Y | A | ND | / | / | / | / | MELAS | Carrying T9185C |
| 53 | 3271 | m.3271T\>C | T3271C\-F7 | T3271C\-F7\-I2 | Uninf | F | N | N | A | 37 | 21\.6% | / | 51% | 71\.6% (F) | Healthy |  |
| 54 | 3271 | m.3271T\>C | T3271C\-F7 | T3271C\-F7\-II1 | Fam | F | Y | Y | A | 3 | 84\.3% | 96\.3% | 95\.6% | 82\.9% (F) | Easy fatigability, myalgia, failure to thrive, short stature, complete growth hormone deficiency, generalized hypotonia, muscle wasting, muscle weakness, positive Gowers sign, reduced tendon reflexes, mild sensory\-neural hearing loss, generalized osteoporosis, epiphyseal knee abnormalities, severely delayed bone age, mild concentric hypertrophic cardiomyopathy, left ventricular hypertrophy |  |
| 55 | 3271 | m.3271T\>C | T3271C\-F8 | T3271C\-F8\-P1 | Uninf | ND | Y | Y | ND | ND | / | 80\~90% | / | / | MELAS |  |
| 56 | 3271 | m.3271T\>C | T3271C\-F9 | T3271C\-F9\-P1 | Uninf | F | Y | Y | A | 36 | / | / | / | / | MELAS |  |
| 57 | 3271 | m.3271T\>C | T3271C\-F10 | T3271C\-F10\-P1 | Uninf | ND | Y | Y | A | 18 | / | 65% | / | / | MELAS |  |

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