Table 1 Clinical features of reported patients with Desmosterolosis
From: Desmosterolosis: an illustration of diagnostic ambiguity of cholesterol synthesis disorders
Feature | Present family | Previously reported cases of desmosterolosis | Frequency (n = 9) | ||||
|---|---|---|---|---|---|---|---|
Patient 1 | Patient 2 | Patient 31 | Patients 4-72 | Patient 83 | Patient 94 | ||
Mutation | c.[571G>A] + [571G>A] p.[E191K] + [E191K] | c.[571G>A] + [571G>A] p.[E191K] + [E191K] | c.[307C>T] + [307C>T] p.[R103C] + [R103C] | c.[281G>A] + [1438G>A] p.[R94H] + [E480K] | c.[1412A>C] + [881A > C;918G>C] p.[Y471S] + [N294T; K306N] | ||
Protein domain | FAD-binding domain | FAD-binding domain | FAD-binding domain | FAD-binding domain + C terminal cytoplasmic domain | C terminal cytoplasmic domain | ||
Ancestry | Middle Eastern | European | Israeli Bedouin | European | |||
Failure to thrive | 1 | 1 | 1 | 4/4 | 1 | n.a. | 8/8 |
Short stature | 1 | 1 | 1 | n.a. | n.a. | 0 | 3/4 |
Microcephaly | 0 | 0 | 1 | 4/4 | 0 | 0 | 5/9 |
Macrocephaly | 0 | 0 | 0 | 0/4 | 1 | 1 | 2/9 |
Microretrognatia | 1 | 0 | 1 | 4/4 | 1 | 1 | 8/9 |
Cleft palate | 1 | 0 | 1 | 0 | 0 | 1 | 3/9 |
Facial features | Dolicocephaly; bitemporal narrowing; low set ears; short downslanting PF; prominent columella; cleft palate | Dolicocephaly; bitemporal narrowing; low set ears; short downslanting PF; prominent columella; | Downslanting PF; bilateral epicanthal folds | Prominent forehead; Short nose; anteverted nares; telecanthus; | Frontal bossing; hypoplastic nose; low set ears; cleft palate | ||
ID/DD | 1 | 1 | 1 | 4/4 | 1 | n.a. | 8/8 |
Spasticity | 1 | 1 | 1 | 4/4 | n.a. | n.a. | 7/7 |
Distal arthrogryposis | 1 | 1 | 1 | 4/4 | 1 | 0 | 8/9 |
Large joint contractures | 0 | 1 (talipes) | 1 (talipes) | n.a. | 1 | 1 | 4/5 |
Shortening of the limbs | 0 | 0 | 0 | n.a. | 1 | 1 | 2/5 |
ACC (partial/full) | 1 | 1 | 1 | 4/4 | 1 | 1 | 9/9 |
Ventriculomegaly | 1 | 1 | 0 | 4/4 | 1 | 1 | 8/9 |
Cerebral WM atrophy | 1 | 1 | 1 | 4/4 | 1 | n.a. | 8/8 |
Cerebellar WM atrophy | 1 | 1 | n.a. | 2/2 | n.a. | n.a. | 4/4 |
Nystagmus /strabismus | 1 | 1 | 0 | 3/4 | 0 | n.a. | 5/8 |
Seizures | 1 | 1 | 0 | 3/4 | n.a. | n.a. | 5/7 |
Other features | SNHL; Hirsutism | Parietal foramina. Hirsutism | Cutis aplasia; Limb anomalies; PDA; | Hydrocephalus | Osteosclerosis; ambiguous genitalia; anomalous pulmonary venous drainage; renal hypoplasia; death at 1 h | ||
Functional assays | Expressed both mutations in c.cerevisiae (separately) with significant ⇩enzyme activity | Expressed mutations in c.cerevisiae with significant ⇩enzyme activity (including compound het) | |||||