Clinical presentation, laboratory investigations and exome sequencing results for 35 patients with unexplained ataxia
| ID, Sex . | Age of onset (y) . | Family history . | Symptom at onset . | Clinical signs . | Investigations . | Gene . | Variants . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cerebellar a ataxia . | Eyes . | Cerebellar dysarthria . | Electrophysiology . | MRI . | ||||||||||||
| Jerky ocular pursuit . | Gaze evoked nystagmus . | Hypometric saccades . | Optic atrophy . | Axonal sensorimotor neuropathy . | Demyelinating sensorimotor neuropathy . | Normal . | Cerebellar atrophy . | Generalized atrophy . | ||||||||
| Confirmed pathogenic | ||||||||||||||||
| P1, M | Teens | Aff sib (P2) | Learning difficulties | + | − | − | − | − | − | + | + | − | + | − | SACS | c.2076delG:p.Thr692Thr fs*713; c.3965_3966delAC:p. Gly1322Valfs*1343s |
| P2, F | 26 | Aff sib (P1) | Upper limb clumsiness | + | + | − | − | − | + | + | + | − | + | + | ||
| P3, M | Teens | Aff sib (P4) | Upper limb clumsiness | + | + | + | + | + | + | − | − | + | − | − | SACS | hemizygous c.13048G>T: p.Glu4350*; 0.7Mb deletion on Chr13q12.12s |
| P4, M | Childhood | Aff sib (P3) | Walking delay | + | + | + | − | + | + | − | − | + | + | + | ||
| P5, M | 40 | Aff sib (P6) | Gait disturbance | + | − | − | − | − | − | − | + | − | − | + | SACS | c.1580C>G:p.Ser527* c.6781C>A:p.Leu2261Iles |
| P6, F | 40s | Aff sib (P5) | Gait disturbance | + | + | − | − | − | + | − | − | − | − | − | ||
| P7, F | 23 | Aff sib (P8) | Speech, balance | + | + | − | − | + | − | − | − | − | + | − | KCNC3 | het. c.1259G>A:p.Arg420Hiss |
| P8, F | 57 | Aff sib (P7) | Upper limb clumsiness | + | + | − | − | + | − | − | − | − | + | − | ||
| P9, M | 30 | Aff sib (P10) | Upper limb clumsiness | + | + | + | − | + | + | − | − | + | − | + | SPG7 | c.1529C>T:p.Ala510Val; c.1715C>T:p.Ala572Val |
| P10, F | 29 | Aff sib (P9) | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | + | − | ||
| P11, F | Infancy | Aff sib (P12), mother (P13) | Delayed motor and speech development | + | − | + | − | + | + | − | − | − | + | − | TUBB4A | het c.900C>A:p.Met300Iles |
| P12, F | Infancy | Aff sib (P11), mother (P13) | Delayed motor and speech development | + | − | + | + | + | + | − | − | − | + | − | ||
| P13, F | 30 | Aff children (P11, P12) | Gait disturbance, slurred speech | + | − | + | − | + | + | − | − | + | + | − | mosaic c.900C>A:p.Met300Iles | |
| P14, F | 5 | None | Learning difficulties, gait disturbance | + | − | − | + | − | + | − | − | + | − | − | TUBB4A | het c.1091C>A:p.Ala364Asps |
| P15, F | 21 | 2 Aff sibs (P17) | Gait disturbance | + | − | − | + | − | + | − | − | + | − | − | NPC1 | c.467T>C: p.Met156Thr c.709C>T:p.Pro237Sers |
| P16, F | 21 | 2 Aff sibs (P16) | Upper limb clumsiness | + | + | − | + | − | + | − | − | + | − | − | ||
| P17, M | 30 | Aff mother, aff cousin (P19) | Speech disturbance Upper limb clumsiness | + | + | − | + | − | + | − | − | − | − | − | SLC1A3 | het c.1361G>A:p.Arg454Glns |
| P18, F | 39 | Aff cousin (P18), aff aunt | Speech disturbance | + | + | − | − | − | + | − | − | − | − | − | ||
| Possibly pathogenic | ||||||||||||||||
| P19, M | 32 | None | Gait disturbance | + | − | − | − | − | − | + | − | − | − | + | ZFYVE26 | c.2338C>T:p.Arg780* |
| c.2450delT:p.Leu817Cysfs*12 | ||||||||||||||||
| P20, F | 40 | None | Gait disturbance | + | − | − | − | + | + | − | − | − | − | − | WFS1 | c.577A>C:p.Lys193Gln; c.1367G>A:p.Arg456His |
| P21, F | Infancy | None | Walking delay | + | − | + | − | + | + | − | − | − | − | − | FASTKD2 | c.-66A>G; c.149A >G:p.Lys50Args |
| P22, M | 37 | Aff son (P23) | Upper limb clumsiness | + | − | + | − | − | + | − | − | − | + | − | ZFYVE27 | c.805-2A>Gs |
| P23, M | 35 | Aff father (P22) | + | − | − | − | − | + | − | − | + | + | − | |||
| P24, M | 25 | Aff father (P22) Aff half-brother (P23) | + | + | + | + | − | + | − | − | − | + | − | |||
| P25, F | 11 | None | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | − | − | WNK1 | c.1994C>T:p.Thr665Iles c.3272C>T:p.Thr1091Iles |
| Uncertain significance or no candidate variants found | ||||||||||||||||
| P26, F | 13 | None | Upper limb clumsiness | + | + | + | + | − | + | − | − | − | − | − | KCNB2 | c.1589C>T: p.Ser530Phe; c.2351T>C:p.Leu784Pro |
| P27, M | 20 | 2 Aff children | Gait disturbance | + | + | + | − | − | + | − | − | − | + | − | ABCB7 | hom (hemi) c.818G >A:p.Arg273Glns |
| POLG | ||||||||||||||||
| WFS1 | c.2243G>C:p.Trp748Ser; c.3428A>G:p.Glu1143Gly | |||||||||||||||
| het c.1294C>G:p.Leu432Val | ||||||||||||||||
| P28, F | Childhood | Aff cousin | Gait disturbance | + | + | + | − | − | − | − | − | − | + | − | No candidate variants | |
| P29, F | 40 | Aff child (P30) | Gait disturbance | + | + | + | − | − | − | − | − | − | − | + | No candidate variants | |
| P30, M | 21 | Aff mother (P29) | Gait disturbance | + | + | − | − | − | − | + | − | − | + | − | No candidate variants | |
| P31, F | 46 | None | Gait disturbance | + | + | − | − | − | + | − | − | − | − | − | No candidate variants | |
| P32, M | 31 | None | Upper limb clumsiness | + | + | + | − | − | + | − | − | − | + | + | No candidate variants | |
| P33, M | Teens | Aff sib (P34) | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | + | − | No candidate variants | |
| P34, M | 11 | Aff sib (P33) | Upper limb clumsiness | + | + | + | + | + | + | − | − | + | + | − | No candidate variants | |
| P35, F | 20 | Mother has hypotonia | Gait disturbance | + | + | + | − | + | − | − | − | − | + | − | No candidate variants | |
| ID, Sex . | Age of onset (y) . | Family history . | Symptom at onset . | Clinical signs . | Investigations . | Gene . | Variants . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cerebellar a ataxia . | Eyes . | Cerebellar dysarthria . | Electrophysiology . | MRI . | ||||||||||||
| Jerky ocular pursuit . | Gaze evoked nystagmus . | Hypometric saccades . | Optic atrophy . | Axonal sensorimotor neuropathy . | Demyelinating sensorimotor neuropathy . | Normal . | Cerebellar atrophy . | Generalized atrophy . | ||||||||
| Confirmed pathogenic | ||||||||||||||||
| P1, M | Teens | Aff sib (P2) | Learning difficulties | + | − | − | − | − | − | + | + | − | + | − | SACS | c.2076delG:p.Thr692Thr fs*713; c.3965_3966delAC:p. Gly1322Valfs*1343s |
| P2, F | 26 | Aff sib (P1) | Upper limb clumsiness | + | + | − | − | − | + | + | + | − | + | + | ||
| P3, M | Teens | Aff sib (P4) | Upper limb clumsiness | + | + | + | + | + | + | − | − | + | − | − | SACS | hemizygous c.13048G>T: p.Glu4350*; 0.7Mb deletion on Chr13q12.12s |
| P4, M | Childhood | Aff sib (P3) | Walking delay | + | + | + | − | + | + | − | − | + | + | + | ||
| P5, M | 40 | Aff sib (P6) | Gait disturbance | + | − | − | − | − | − | − | + | − | − | + | SACS | c.1580C>G:p.Ser527* c.6781C>A:p.Leu2261Iles |
| P6, F | 40s | Aff sib (P5) | Gait disturbance | + | + | − | − | − | + | − | − | − | − | − | ||
| P7, F | 23 | Aff sib (P8) | Speech, balance | + | + | − | − | + | − | − | − | − | + | − | KCNC3 | het. c.1259G>A:p.Arg420Hiss |
| P8, F | 57 | Aff sib (P7) | Upper limb clumsiness | + | + | − | − | + | − | − | − | − | + | − | ||
| P9, M | 30 | Aff sib (P10) | Upper limb clumsiness | + | + | + | − | + | + | − | − | + | − | + | SPG7 | c.1529C>T:p.Ala510Val; c.1715C>T:p.Ala572Val |
| P10, F | 29 | Aff sib (P9) | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | + | − | ||
| P11, F | Infancy | Aff sib (P12), mother (P13) | Delayed motor and speech development | + | − | + | − | + | + | − | − | − | + | − | TUBB4A | het c.900C>A:p.Met300Iles |
| P12, F | Infancy | Aff sib (P11), mother (P13) | Delayed motor and speech development | + | − | + | + | + | + | − | − | − | + | − | ||
| P13, F | 30 | Aff children (P11, P12) | Gait disturbance, slurred speech | + | − | + | − | + | + | − | − | + | + | − | mosaic c.900C>A:p.Met300Iles | |
| P14, F | 5 | None | Learning difficulties, gait disturbance | + | − | − | + | − | + | − | − | + | − | − | TUBB4A | het c.1091C>A:p.Ala364Asps |
| P15, F | 21 | 2 Aff sibs (P17) | Gait disturbance | + | − | − | + | − | + | − | − | + | − | − | NPC1 | c.467T>C: p.Met156Thr c.709C>T:p.Pro237Sers |
| P16, F | 21 | 2 Aff sibs (P16) | Upper limb clumsiness | + | + | − | + | − | + | − | − | + | − | − | ||
| P17, M | 30 | Aff mother, aff cousin (P19) | Speech disturbance Upper limb clumsiness | + | + | − | + | − | + | − | − | − | − | − | SLC1A3 | het c.1361G>A:p.Arg454Glns |
| P18, F | 39 | Aff cousin (P18), aff aunt | Speech disturbance | + | + | − | − | − | + | − | − | − | − | − | ||
| Possibly pathogenic | ||||||||||||||||
| P19, M | 32 | None | Gait disturbance | + | − | − | − | − | − | + | − | − | − | + | ZFYVE26 | c.2338C>T:p.Arg780* |
| c.2450delT:p.Leu817Cysfs*12 | ||||||||||||||||
| P20, F | 40 | None | Gait disturbance | + | − | − | − | + | + | − | − | − | − | − | WFS1 | c.577A>C:p.Lys193Gln; c.1367G>A:p.Arg456His |
| P21, F | Infancy | None | Walking delay | + | − | + | − | + | + | − | − | − | − | − | FASTKD2 | c.-66A>G; c.149A >G:p.Lys50Args |
| P22, M | 37 | Aff son (P23) | Upper limb clumsiness | + | − | + | − | − | + | − | − | − | + | − | ZFYVE27 | c.805-2A>Gs |
| P23, M | 35 | Aff father (P22) | + | − | − | − | − | + | − | − | + | + | − | |||
| P24, M | 25 | Aff father (P22) Aff half-brother (P23) | + | + | + | + | − | + | − | − | − | + | − | |||
| P25, F | 11 | None | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | − | − | WNK1 | c.1994C>T:p.Thr665Iles c.3272C>T:p.Thr1091Iles |
| Uncertain significance or no candidate variants found | ||||||||||||||||
| P26, F | 13 | None | Upper limb clumsiness | + | + | + | + | − | + | − | − | − | − | − | KCNB2 | c.1589C>T: p.Ser530Phe; c.2351T>C:p.Leu784Pro |
| P27, M | 20 | 2 Aff children | Gait disturbance | + | + | + | − | − | + | − | − | − | + | − | ABCB7 | hom (hemi) c.818G >A:p.Arg273Glns |
| POLG | ||||||||||||||||
| WFS1 | c.2243G>C:p.Trp748Ser; c.3428A>G:p.Glu1143Gly | |||||||||||||||
| het c.1294C>G:p.Leu432Val | ||||||||||||||||
| P28, F | Childhood | Aff cousin | Gait disturbance | + | + | + | − | − | − | − | − | − | + | − | No candidate variants | |
| P29, F | 40 | Aff child (P30) | Gait disturbance | + | + | + | − | − | − | − | − | − | − | + | No candidate variants | |
| P30, M | 21 | Aff mother (P29) | Gait disturbance | + | + | − | − | − | − | + | − | − | + | − | No candidate variants | |
| P31, F | 46 | None | Gait disturbance | + | + | − | − | − | + | − | − | − | − | − | No candidate variants | |
| P32, M | 31 | None | Upper limb clumsiness | + | + | + | − | − | + | − | − | − | + | + | No candidate variants | |
| P33, M | Teens | Aff sib (P34) | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | + | − | No candidate variants | |
| P34, M | 11 | Aff sib (P33) | Upper limb clumsiness | + | + | + | + | + | + | − | − | + | + | − | No candidate variants | |
| P35, F | 20 | Mother has hypotonia | Gait disturbance | + | + | + | − | + | − | − | − | − | + | − | No candidate variants | |
M = male; F = female; Hom = homozygous; Het = heterozygous; ‘+’ = present; ‘-’ = absent, not applicable (test not carried out); sib = sibling; aff = affected; N = normal (all results normal/negative).
sSegregation analysis performed in the family.
Two have been reported previously (Pyle et al., 2012, 2013).
Clinical presentation, laboratory investigations and exome sequencing results for 35 patients with unexplained ataxia
| ID, Sex . | Age of onset (y) . | Family history . | Symptom at onset . | Clinical signs . | Investigations . | Gene . | Variants . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cerebellar a ataxia . | Eyes . | Cerebellar dysarthria . | Electrophysiology . | MRI . | ||||||||||||
| Jerky ocular pursuit . | Gaze evoked nystagmus . | Hypometric saccades . | Optic atrophy . | Axonal sensorimotor neuropathy . | Demyelinating sensorimotor neuropathy . | Normal . | Cerebellar atrophy . | Generalized atrophy . | ||||||||
| Confirmed pathogenic | ||||||||||||||||
| P1, M | Teens | Aff sib (P2) | Learning difficulties | + | − | − | − | − | − | + | + | − | + | − | SACS | c.2076delG:p.Thr692Thr fs*713; c.3965_3966delAC:p. Gly1322Valfs*1343s |
| P2, F | 26 | Aff sib (P1) | Upper limb clumsiness | + | + | − | − | − | + | + | + | − | + | + | ||
| P3, M | Teens | Aff sib (P4) | Upper limb clumsiness | + | + | + | + | + | + | − | − | + | − | − | SACS | hemizygous c.13048G>T: p.Glu4350*; 0.7Mb deletion on Chr13q12.12s |
| P4, M | Childhood | Aff sib (P3) | Walking delay | + | + | + | − | + | + | − | − | + | + | + | ||
| P5, M | 40 | Aff sib (P6) | Gait disturbance | + | − | − | − | − | − | − | + | − | − | + | SACS | c.1580C>G:p.Ser527* c.6781C>A:p.Leu2261Iles |
| P6, F | 40s | Aff sib (P5) | Gait disturbance | + | + | − | − | − | + | − | − | − | − | − | ||
| P7, F | 23 | Aff sib (P8) | Speech, balance | + | + | − | − | + | − | − | − | − | + | − | KCNC3 | het. c.1259G>A:p.Arg420Hiss |
| P8, F | 57 | Aff sib (P7) | Upper limb clumsiness | + | + | − | − | + | − | − | − | − | + | − | ||
| P9, M | 30 | Aff sib (P10) | Upper limb clumsiness | + | + | + | − | + | + | − | − | + | − | + | SPG7 | c.1529C>T:p.Ala510Val; c.1715C>T:p.Ala572Val |
| P10, F | 29 | Aff sib (P9) | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | + | − | ||
| P11, F | Infancy | Aff sib (P12), mother (P13) | Delayed motor and speech development | + | − | + | − | + | + | − | − | − | + | − | TUBB4A | het c.900C>A:p.Met300Iles |
| P12, F | Infancy | Aff sib (P11), mother (P13) | Delayed motor and speech development | + | − | + | + | + | + | − | − | − | + | − | ||
| P13, F | 30 | Aff children (P11, P12) | Gait disturbance, slurred speech | + | − | + | − | + | + | − | − | + | + | − | mosaic c.900C>A:p.Met300Iles | |
| P14, F | 5 | None | Learning difficulties, gait disturbance | + | − | − | + | − | + | − | − | + | − | − | TUBB4A | het c.1091C>A:p.Ala364Asps |
| P15, F | 21 | 2 Aff sibs (P17) | Gait disturbance | + | − | − | + | − | + | − | − | + | − | − | NPC1 | c.467T>C: p.Met156Thr c.709C>T:p.Pro237Sers |
| P16, F | 21 | 2 Aff sibs (P16) | Upper limb clumsiness | + | + | − | + | − | + | − | − | + | − | − | ||
| P17, M | 30 | Aff mother, aff cousin (P19) | Speech disturbance Upper limb clumsiness | + | + | − | + | − | + | − | − | − | − | − | SLC1A3 | het c.1361G>A:p.Arg454Glns |
| P18, F | 39 | Aff cousin (P18), aff aunt | Speech disturbance | + | + | − | − | − | + | − | − | − | − | − | ||
| Possibly pathogenic | ||||||||||||||||
| P19, M | 32 | None | Gait disturbance | + | − | − | − | − | − | + | − | − | − | + | ZFYVE26 | c.2338C>T:p.Arg780* |
| c.2450delT:p.Leu817Cysfs*12 | ||||||||||||||||
| P20, F | 40 | None | Gait disturbance | + | − | − | − | + | + | − | − | − | − | − | WFS1 | c.577A>C:p.Lys193Gln; c.1367G>A:p.Arg456His |
| P21, F | Infancy | None | Walking delay | + | − | + | − | + | + | − | − | − | − | − | FASTKD2 | c.-66A>G; c.149A >G:p.Lys50Args |
| P22, M | 37 | Aff son (P23) | Upper limb clumsiness | + | − | + | − | − | + | − | − | − | + | − | ZFYVE27 | c.805-2A>Gs |
| P23, M | 35 | Aff father (P22) | + | − | − | − | − | + | − | − | + | + | − | |||
| P24, M | 25 | Aff father (P22) Aff half-brother (P23) | + | + | + | + | − | + | − | − | − | + | − | |||
| P25, F | 11 | None | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | − | − | WNK1 | c.1994C>T:p.Thr665Iles c.3272C>T:p.Thr1091Iles |
| Uncertain significance or no candidate variants found | ||||||||||||||||
| P26, F | 13 | None | Upper limb clumsiness | + | + | + | + | − | + | − | − | − | − | − | KCNB2 | c.1589C>T: p.Ser530Phe; c.2351T>C:p.Leu784Pro |
| P27, M | 20 | 2 Aff children | Gait disturbance | + | + | + | − | − | + | − | − | − | + | − | ABCB7 | hom (hemi) c.818G >A:p.Arg273Glns |
| POLG | ||||||||||||||||
| WFS1 | c.2243G>C:p.Trp748Ser; c.3428A>G:p.Glu1143Gly | |||||||||||||||
| het c.1294C>G:p.Leu432Val | ||||||||||||||||
| P28, F | Childhood | Aff cousin | Gait disturbance | + | + | + | − | − | − | − | − | − | + | − | No candidate variants | |
| P29, F | 40 | Aff child (P30) | Gait disturbance | + | + | + | − | − | − | − | − | − | − | + | No candidate variants | |
| P30, M | 21 | Aff mother (P29) | Gait disturbance | + | + | − | − | − | − | + | − | − | + | − | No candidate variants | |
| P31, F | 46 | None | Gait disturbance | + | + | − | − | − | + | − | − | − | − | − | No candidate variants | |
| P32, M | 31 | None | Upper limb clumsiness | + | + | + | − | − | + | − | − | − | + | + | No candidate variants | |
| P33, M | Teens | Aff sib (P34) | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | + | − | No candidate variants | |
| P34, M | 11 | Aff sib (P33) | Upper limb clumsiness | + | + | + | + | + | + | − | − | + | + | − | No candidate variants | |
| P35, F | 20 | Mother has hypotonia | Gait disturbance | + | + | + | − | + | − | − | − | − | + | − | No candidate variants | |
| ID, Sex . | Age of onset (y) . | Family history . | Symptom at onset . | Clinical signs . | Investigations . | Gene . | Variants . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cerebellar a ataxia . | Eyes . | Cerebellar dysarthria . | Electrophysiology . | MRI . | ||||||||||||
| Jerky ocular pursuit . | Gaze evoked nystagmus . | Hypometric saccades . | Optic atrophy . | Axonal sensorimotor neuropathy . | Demyelinating sensorimotor neuropathy . | Normal . | Cerebellar atrophy . | Generalized atrophy . | ||||||||
| Confirmed pathogenic | ||||||||||||||||
| P1, M | Teens | Aff sib (P2) | Learning difficulties | + | − | − | − | − | − | + | + | − | + | − | SACS | c.2076delG:p.Thr692Thr fs*713; c.3965_3966delAC:p. Gly1322Valfs*1343s |
| P2, F | 26 | Aff sib (P1) | Upper limb clumsiness | + | + | − | − | − | + | + | + | − | + | + | ||
| P3, M | Teens | Aff sib (P4) | Upper limb clumsiness | + | + | + | + | + | + | − | − | + | − | − | SACS | hemizygous c.13048G>T: p.Glu4350*; 0.7Mb deletion on Chr13q12.12s |
| P4, M | Childhood | Aff sib (P3) | Walking delay | + | + | + | − | + | + | − | − | + | + | + | ||
| P5, M | 40 | Aff sib (P6) | Gait disturbance | + | − | − | − | − | − | − | + | − | − | + | SACS | c.1580C>G:p.Ser527* c.6781C>A:p.Leu2261Iles |
| P6, F | 40s | Aff sib (P5) | Gait disturbance | + | + | − | − | − | + | − | − | − | − | − | ||
| P7, F | 23 | Aff sib (P8) | Speech, balance | + | + | − | − | + | − | − | − | − | + | − | KCNC3 | het. c.1259G>A:p.Arg420Hiss |
| P8, F | 57 | Aff sib (P7) | Upper limb clumsiness | + | + | − | − | + | − | − | − | − | + | − | ||
| P9, M | 30 | Aff sib (P10) | Upper limb clumsiness | + | + | + | − | + | + | − | − | + | − | + | SPG7 | c.1529C>T:p.Ala510Val; c.1715C>T:p.Ala572Val |
| P10, F | 29 | Aff sib (P9) | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | + | − | ||
| P11, F | Infancy | Aff sib (P12), mother (P13) | Delayed motor and speech development | + | − | + | − | + | + | − | − | − | + | − | TUBB4A | het c.900C>A:p.Met300Iles |
| P12, F | Infancy | Aff sib (P11), mother (P13) | Delayed motor and speech development | + | − | + | + | + | + | − | − | − | + | − | ||
| P13, F | 30 | Aff children (P11, P12) | Gait disturbance, slurred speech | + | − | + | − | + | + | − | − | + | + | − | mosaic c.900C>A:p.Met300Iles | |
| P14, F | 5 | None | Learning difficulties, gait disturbance | + | − | − | + | − | + | − | − | + | − | − | TUBB4A | het c.1091C>A:p.Ala364Asps |
| P15, F | 21 | 2 Aff sibs (P17) | Gait disturbance | + | − | − | + | − | + | − | − | + | − | − | NPC1 | c.467T>C: p.Met156Thr c.709C>T:p.Pro237Sers |
| P16, F | 21 | 2 Aff sibs (P16) | Upper limb clumsiness | + | + | − | + | − | + | − | − | + | − | − | ||
| P17, M | 30 | Aff mother, aff cousin (P19) | Speech disturbance Upper limb clumsiness | + | + | − | + | − | + | − | − | − | − | − | SLC1A3 | het c.1361G>A:p.Arg454Glns |
| P18, F | 39 | Aff cousin (P18), aff aunt | Speech disturbance | + | + | − | − | − | + | − | − | − | − | − | ||
| Possibly pathogenic | ||||||||||||||||
| P19, M | 32 | None | Gait disturbance | + | − | − | − | − | − | + | − | − | − | + | ZFYVE26 | c.2338C>T:p.Arg780* |
| c.2450delT:p.Leu817Cysfs*12 | ||||||||||||||||
| P20, F | 40 | None | Gait disturbance | + | − | − | − | + | + | − | − | − | − | − | WFS1 | c.577A>C:p.Lys193Gln; c.1367G>A:p.Arg456His |
| P21, F | Infancy | None | Walking delay | + | − | + | − | + | + | − | − | − | − | − | FASTKD2 | c.-66A>G; c.149A >G:p.Lys50Args |
| P22, M | 37 | Aff son (P23) | Upper limb clumsiness | + | − | + | − | − | + | − | − | − | + | − | ZFYVE27 | c.805-2A>Gs |
| P23, M | 35 | Aff father (P22) | + | − | − | − | − | + | − | − | + | + | − | |||
| P24, M | 25 | Aff father (P22) Aff half-brother (P23) | + | + | + | + | − | + | − | − | − | + | − | |||
| P25, F | 11 | None | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | − | − | WNK1 | c.1994C>T:p.Thr665Iles c.3272C>T:p.Thr1091Iles |
| Uncertain significance or no candidate variants found | ||||||||||||||||
| P26, F | 13 | None | Upper limb clumsiness | + | + | + | + | − | + | − | − | − | − | − | KCNB2 | c.1589C>T: p.Ser530Phe; c.2351T>C:p.Leu784Pro |
| P27, M | 20 | 2 Aff children | Gait disturbance | + | + | + | − | − | + | − | − | − | + | − | ABCB7 | hom (hemi) c.818G >A:p.Arg273Glns |
| POLG | ||||||||||||||||
| WFS1 | c.2243G>C:p.Trp748Ser; c.3428A>G:p.Glu1143Gly | |||||||||||||||
| het c.1294C>G:p.Leu432Val | ||||||||||||||||
| P28, F | Childhood | Aff cousin | Gait disturbance | + | + | + | − | − | − | − | − | − | + | − | No candidate variants | |
| P29, F | 40 | Aff child (P30) | Gait disturbance | + | + | + | − | − | − | − | − | − | − | + | No candidate variants | |
| P30, M | 21 | Aff mother (P29) | Gait disturbance | + | + | − | − | − | − | + | − | − | + | − | No candidate variants | |
| P31, F | 46 | None | Gait disturbance | + | + | − | − | − | + | − | − | − | − | − | No candidate variants | |
| P32, M | 31 | None | Upper limb clumsiness | + | + | + | − | − | + | − | − | − | + | + | No candidate variants | |
| P33, M | Teens | Aff sib (P34) | Upper limb clumsiness | + | − | + | − | − | + | − | − | + | + | − | No candidate variants | |
| P34, M | 11 | Aff sib (P33) | Upper limb clumsiness | + | + | + | + | + | + | − | − | + | + | − | No candidate variants | |
| P35, F | 20 | Mother has hypotonia | Gait disturbance | + | + | + | − | + | − | − | − | − | + | − | No candidate variants | |
M = male; F = female; Hom = homozygous; Het = heterozygous; ‘+’ = present; ‘-’ = absent, not applicable (test not carried out); sib = sibling; aff = affected; N = normal (all results normal/negative).
sSegregation analysis performed in the family.
Two have been reported previously (Pyle et al., 2012, 2013).
This PDF is available to Subscribers Only
View Article Abstract & Purchase OptionsFor full access to this pdf, sign in to an existing account, or purchase an annual subscription.
