Table 3.
Phenotypes Seen in Carriers of Rare Variants in PHIP, DGKI, and ZMYM4
| Variant | Age (Years) | Sex | BMI (SDS) | Height (SDS) | Bwt SDS | Learning Difficulties | Dysmorphic Features | Autistic Features | Hyperactivity | Aggression | Anxiety or Depression | Insulin (pmol/L) | Glucose (mmol/L) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PHIP | |||||||||||||
| R250Xa | 6 | F | 25 (3.6) | 111 (−0.9) | 0.6 | ||||||||
| T289P | 7.7 | F | 34 (4.2) | 133 (1.3) | 1.5 | ✓ | ✓ | 134 | 3.8 | ||||
| A389T | 5.1 | F | 40 (6.0) | 114 (1.1) | 2.2 | 146 | 4.7 | ||||||
| A389Tb | 46 | M | 54 | 173 | 171 | 5.3 | |||||||
| R409C | 1.4 | F | 24 (3.7) | 84 (1.6) | −2.9 | ✓ | ✓ | ✓ | ✓ | 47 | 5.1 | ||
| R409Cb | 34 | M | 38 | 175 | |||||||||
| R721X | 44.3 | F | 74 | 150 | @ | 9.1 | |||||||
| Q1343X | 17.2 | F | 43 (3.8) | 151 (−2.1) | −0.1 | ✓ | ✓ | 208c | 5.9 | ||||
| F1414Sa | 20.7 | M | 40 | 188 | −0.9 | ✓ | ✓ | ✓ | ✓ | ✓ | 398c | 6 | |
| K1443TfsX11 | 7.6 | F | 35 (4.3) | 119 (−1.1) | 1.7 | ✓ | ✓ | 42 | 4.4 | ||||
| T1506A | 2.4 | F | 23 (3.8) | 102 (3.8) | 1.6 | ✓ | 292 | 5.8 | |||||
| T1506Ab | 44 | M | 21 | ||||||||||
| T1506A | 15 | M | 46 (4.0) | 168 (−0.1) | 0 | ✓ | 98 | 5.1 | |||||
| T1506Ab | 54 | M | 29 | ||||||||||
| R1718S | 22.7 | M | 40 | 170 | −1.8 | 100 | 5.4 | ||||||
| c.823-2A>G | 7.9 | M | 27 (3.5) | 135 (1.4) | 0.3 | ✓ | ✓ | ✓ | 57 | 5.5 | |||
| c.1524+1G>T | 15.5 | M | 35 (3.2) | 176 (0.6) | 0.23 | ✓ | ✓ | 154 | 5.2 | ||||
| c.3536-4_3540 delTTA GATATTa |
13.1 | F | 49 (4.2) | 161 (0.7) | −0.9 | ✓ | 144 | 5.3 | |||||
| DGKI | |||||||||||||
| D833N | 15.3 | F | 45 (4.0) | 166 (0.5) | −0.2 | 144 | 4.6 | ||||||
| L430R | 9.1 | F | 26 (2.9) | 132 (−0.2) | 1.3 | ||||||||
| Q265X | 3.6 | M | 22 (3.6) | 113 (3.3) | −0.8 | ✓σ | 32 | 4.7 | |||||
| L192F | 12.6 | M | 31 (3.1) | 151 (−0.1) | −0.1 | 41 | 3.1 | ||||||
| ZMYM4 | |||||||||||||
| N89S | 15.5 | F | 39 (3.5) | 161 (−0.4) | 0.1 | ✓ | 136 | 4.6 | |||||
| K163Rfsx10 | 11.1 | M | 28.3 (3.0) | 152 (1.2) | 0.1 | 24 | 4.2 | ||||||
| R379C | 1.2 | F | 26 (4.5) | 84 (3.0) | 0.5 | 36 | |||||||
| K387N | 7.8 | M | 25 (3.3) | 131 (0.8) | 0.6 | ✓ | 30 | 3.9 | |||||
M, male; F, female. BMI (kg/m2) shown for adults with age- and gender-adjusted standard deviation scores (SDS) shown in brackets for children under 18 years of age at referral. Height in cm (SDS). Birthweight (Bwt) SDS adjusted for gestational age. ✓ indicates reported presence of a phenotype. Fasting values for glucose and insulin reported: normal range for fasting plasma insulin = 0–60 pmol/L. @, on medication for type 2 diabetes. Speech and language delay represented as ✓σ.
a
De novo inheritance established by genotyping both parents.
b
Rare coding in family member.
c
Presence of acanthosis nigricans (skin marker of insulin resistance).