Table 1.
Summary of clinical presentations, and CMA and molecular findings in nine individuals with TRIP12 mutations
| Subject 1 | Subject 2 | Subject 3 | Subject 4 | Subject 5 | Subject 6 | Subject 7 | Subject 8 | Subject 9 | Summary from this study | Summary from Bramswig et al.) | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Gender | Male | Male | Male | Female | Female | Male | Male | Female | Male | 6 males, 3 females | 7 males, 4 females |
| Age at examination (years) | 15 | 7 | 15 | 4 | 1.8 | 4 | 10 | 12.5 | 7 | 1.8 to 15 | 5.7 to 26.3 |
|
TRIP12 Variant
(NM_004238) Genomic coordinates (min/max, hg19) |
Deletion of 9 exons
(30–38) chr2:230,634,390/230,636,077–230,654,539/230,655,748 |
Deletion of 17 exons
(25–41) chr2: 230,631,958/230,632,049–230,660,565/230,661,210 |
Deletion of 4 exons
(2–5) chr2:230, 230,679,862/698,794–230,781,114/230,801,002 |
Deletion of TRIP12 and
adjacent 7
genes chr2:230,489,478/230,513,445–231,457,431/231,508,839 |
Deletion of TRIP12 and 3
adjacent
genes chr2:229,076,749/229,152,599–230,801,061/230,811,273 |
Frameshift c.3446_3447delCA
(p.S1149*X) Chr2: 230,661,450 |
Frameshift c.2979dupA (p.G994Rfs*5) Chr2: 230,666,969 |
Missense c.2282C>T (p.A761V) Chr2: 230,672,494 |
Splicing c.3743+1G>A Chr2: 230,659,894 |
5 CNVs (microdeletions) 3 SNVs/indels (2 truncating, 1 missense) |
1 translocation 10 SNVs/indels (5 truncating, 5 missense) |
| Ethnicity | Mexican | NA | NA | Caucasian | NA | Saudi Arabia | United Arab Emirates (second cousins parents) | North European/Caucasian | Caucasian | ||
| Inheritance | de novo | Unknown | Unknown | de novo | de novo | de novo | de novo | de novo | de novo | 7 de novo, 2 parents NA | 9 de novo 2 parents NA |
| Maternal age at birth (years) | 45 | NA | NA | NA | NA | 25 | 25 | 26 | 29 | 25–45 | 22–34 |
| Paternal age at birth (years) | 47 | NA | NA | NA | NA | 35 | 27 | 34 | 48 | 27–48 | 25–41 |
| DD/ID | + | + | + | + | + | + | + | + | + | 9/9 | 11/11 |
| Speech delay | + | + | ND | + | + | +. | + | + | + | 8/8 | 10/11 1 ND |
| Autistic behaviors | + Poor social interaction | − | ND | +. Stereotypic behaviors |
+ | +. | +. | +. | − | 6/8 | 8/11 |
| Other behavioral anomalies | Hyper anxiety. Untypical behaviors | ND | Repetitive, aggressive behaviors/sensory issues | Hyperactive and destructive behavior | ND | Extremely impulsive and aggressive behaviors. | − | 6/7 | 8/11 | ||
| First words (months) | 36 | 60 | ND | 24 | ND | ND | ND | 24 | 42 | ||
| Verbal ability | Fluent speech | <100 words at 7 years | ND | 30 words | 5–6 words | No words | single words | Phrase speech | Few phrase speech | 1/8 fluent speech 6/8 phrase or single words 1/8 no words |
6/11 fluent speech 5/11 phrase or single words |
| Motor delay | + | − | ND | + | + | + | + | + | + | 7/8 | 7/11 |
| Walking independently (months) | 15 | ND | ND | 20 | ND | ND | 22 | 23 | 29 | 15–29 | 13–23 |
| Seizures | − | − | ND | − | + | − | − | − | − | 1/8 | 3/11 |
| Microcephaly/OFC (cm) (percentile) | + 52.2 (2–10%) |
ND | ND | + 49 (25%) |
− | ND | − | − | − | 2/6 | 0/11 1 ND |
| Obesity/Weight (kg, percentile) | + 86kg (morbid obesity) |
− 23.3kg (BMI 91%) |
ND | + | − 65% |
ND | + 97% |
+ 90% |
− 50–75% |
4/7 | 2/11 |
| Height (cm) | 174 (75–90%) | 113.5 (6%) | ND | 103 (50%) | 89 (46%) | ND | ND | ND | 123 (75%) | Variable | Variable |
| Dysmorphic features | |||||||||||
| Head shape | Brachycephaly, dolichocephaly | − | ND | − | − | Sloping forehead | − | − | − | 2/8 | ND |
| Narrow palpebral fissures | + | − | ND | − | + | − | + | + | ND | 4/7 | ND |
| Downturned mouth corners | + | − | ND | − | + | − | + | + | − | 4/8 | ND |
| Wide month | + | − | ND | − | − | − | + | + | − | 3/8 | 3/8 |
| Hypertelorism | + | − | ND | − | − | − | − | − | − | 1/8 | 1/8 |
| Epicanthic folds | − | − | ND | + | + | − | + | − | − | 3/8 | 1/8 |
| Depressed nasal bridge | − | − | ND | − | − | − (high nasal bridge) | − | − | − | 0/8 | 1/8 |
| Short nose | − (long nose) | − | ND | − | − | − | − | − | − | 0/8 | 2/8 |
| Anteverted nares | − | − | ND | + | − | − | − | − | − | 1/8 | 1/8 |
| Low hanging columella | + | − | ND | − | − | − | − | − | − | 1/8 | 3/8 |
| Long philtrum | − | − | ND | − | − | − | − | − (short philtrum) | − | 0/8 | 2/8 |
| Smooth philtrum | − | − | ND | − | − | − | − | − | − | 0/8 | 2/8 |
| Thin upper lip vermilion | − (full lips) | − | ND | − | − | − | + | − | − | 1/8 | 2/8 |
| Exaggerated Cupid’s bow | − | − | ND | − | − | − | − | − | − | 0/8 | 4/8 |
| Pointed chin | − | − | ND | − | − | + | − | + | − | 2/8 | ND |
| Large ear lobe | + | − | ND | − | − | + | − | − | + | 3/8 | 3/8 |
| Low set ears | − | − | ND | − | + | − | − | − | − | 1/8 | 2/8 |
| Hand anomalies | − | − | − | − | − | − | spindle shaped fingers | − | − | ||
| Hearing loss (HL) | − | − | − | + Unilateal HL |
− | − | − | − | − | 1/9 | 0/11 |
| Brain anomalies | ND | − | ND | − | − | ND | ND | − | − | ||
Abbreviations are as follows: NA, not available; ND, not determined because of non-availability or non-applicability.