Table 1 Clinical details and genotypes of individuals with Perrault syndrome associated with variants in HARS2.
Individual ID | Family 1 from Pierce et al. [3] | Individual IV-1 from Lerat et al. [11] | Individual VI-1 from Lerat et al. [11] | Family 1 from Karstensen et al. [12] | Family 2 from Karstensen et al. [12] | Family 3 from Karstensen et al. [12] | F1-II-1 (this study) | F2-II-1 (this study) | F2-II-2 (this study) | F3-II-1 (this study) |
|---|---|---|---|---|---|---|---|---|---|---|
Variant | c.598C>G p.(Leu200Val); c.1102G>T p.(Val368Leu) | Homozygous c.1010A>G p.(Tyr337Cys) | Homozygous c.1010A>G p.(Tyr337Cys) | c.172A>G p.(Lys58Glu); c.448C>T p.(Arg150Cys) | c.448C>T p.(Arg150Cys); c.980G>A p.(Arg327Gln) | c.137T>A p.(Leu46Gln); c.259C>T p.(Arg87Cys) | c.413G>A p.(Arg138His); c.1439G>A, p.(Arg480His) | c.828delTinsGTATCCCTAGTATTTCTACTA (p.Gly277TyrfsTer3); c.1439G>A, p.(Arg480His) | c.72C>A, p.Cys24Stop; c.1439G>A, p.(Arg480His) | |
Reference | Pierce et al. [3] | Lerat et al. [11] | Karstensen et al. [12] | This report | ||||||
Ethnicity | Mixed European | Moroccan | Moroccan | European | European | European | European | North American | North American | North American |
Consanguinity | No | Yes | Yes | No | No | No | No | No | No | No |
Sex | M and F (5 affected) | F | F | M and F (3 affected) | F | F | F | M | M | M |
Karyotype | 46, XX for 3 affected females | NR | NR | NR | NR | NR | 46, XX | N/A | N/A | N/A |
Age (years) at last assessment | Variable (13–37) | NR | NR | Variable (18–13) | 7 | 32 | 6 | 14 | 11 | 4 |
Sensorineural hearing loss | ||||||||||
Age at detection (years) | Variable (3–31) | <3 | <3 | Variable (5 years–3 months) | 2 | 2.5 | 6 | 2.5 | 1 | 1.5 |
Degree of hearing loss | Variable severity | Profound | Profound | Moderate/severe | Moderate/severe | Moderate | Moderate | Severe/profound | Severe/profound | Profound |
Course of hearing loss | Progressive | None | None | Rapidly progressive | Rapidly progressive | Rapidly progressive | None | Progressive | Progressive | None |
Hearing habilitation | Not recorded | Not recorded | Not recorded | Bilateral CI | Bilateral CI | Bilateral CI | HA | CI + HA | CI + HA | Not recorded |
Gonadal dysfunction | ||||||||||
POI | Ovarian dysgenesis, with amenorrhea and streak gonads | Secondary amenorrhea, 25 years at onset | Secondary amenorrhea, 26 years at onset | One affected female has irregular menses at 16 years of age | N/A | Secondary amenorrhea, cessation of menses at 24 years | N/A | N/A | N/A | N/A |
Notes | Affected males are fertile | None | None | None | None | None | None | None | None | None |
Neurological features | None reported | None reported | None reported | None reported | None reported | None reported | None reported | One male has very tight muscles in his lower limbs, one has fine motor issues | None | |
Additional features | None reported | Hypothyroidism | Hypothyroidism | None reported | None reported | None reported | None reported | None reported | None reported | None reported |
