Table 2 Clinical features of all reported patients with HARS2 variants
Patient | Origin/ Descent | HARS2 Variants | Sex | Age of Onset | Age at Exam | Degree of hearing loss | Hearing habilitation | Gonadal dysfunction | Age at POI | Neurological features | Additional features | Reference | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
M1 | M2 | |||||||||||||
Family 1 | II-1 | European | c.598C > G p.Leu200Val | c.1102G > T p.Val368Leu | F | 34 | NR | Mild | NR | ovarian dysgenesis, with amenorrhea and streak gonads | NR | NO | NO | Pierce et.al [1] |
II-2 | M | 6 | 22 | Moderate to severe | NR | NA | NA | NO | NO | |||||
II-4 | M | 18 | NR | Moderate to severe | NR | NA | NA | NO | NO | |||||
II-7 | F | 12 | 19 | Mild to moderate | NR | ovarian dysgenesis, with amenorrhea and streak gonads | NR | NO | NO | |||||
II-8 | F | 8 | 13 | Moderate to profound | NR | ovarian dysgenesis, with amenorrhea and streak gonads | NR | NO | NO | |||||
Family 2 | IV-1 | Morocco | c.1010A > G p.Tyr337Cys | (Hom) | F | < 3 | NR | Profound | NR | Secondary Amenorrhea | 25 | NO | Hypothyroidism | Lerat et.al [4] |
VI-1 | F | < 3 | NR | Profound | NR | Secondary Amenorrhea | 26 | NO | Hypothyroidism | |||||
Family 3 | proband | Chinese Han | c.647G > A p.Arg216Gln | c.697C > T p.Arg233Cys | M | NR | NR | NR | NA | NA | NO | NO | NO | Zou et.al [10] |
Family 4 | Proband | European | c.137 T > A p.Leu46Gln | c.259C > T p.Arg87Cys | F | 2.5 | 32 | Moderate | Bilateral CI | Secondary amenorrhea, cessation | 24 | NO | NO | Karstensen et.al [12] |
Family 5 | II-1 | European | c.172A > G p.Lys58Glu | c.448C > T p.Arg150Cys | M | 5 | 18 | Moderate to severe | Bilateral CI | NA | NA | NO | NO | Karstensen et.al [12] |
II-2 | F | 2.6 | 16 | Moderate to severe | Bilateral CI | irregular menses | 16 | NO | NO | |||||
II-3 | F | 0.3 | 13 | Moderate to severe | Bilateral CI | asymptomatic | 13 | NO | NO | |||||
Family 6 | Proband | European | c.448C > T p.Arg150Cys | c.980G > A p.Arg327Gln | F | 2 | 7 | Moderate to severe | Bilateral CI | asymptomatic | 7 | NO | NO | Karstensen et.al [12] |
Family 7 | Proband | European | c.413G > A p.Arg138His | c.1439G > A p.Arg480His | F | 6 | 6 | Moderate | HA | asymptomatic | NR | NO | NO | Demain et.al [11] |
Family 8 | II-1 | North American | c.828delTinsGTATCCCTAGTATTTCTACTA p.Gly277TyrfsTer3 | c.1439G > A p.Arg480His | M | 2.5 | 14 | Severe to profound | CI + HA | NA | NA | Difficulty with fine motor movements | Problems with tooth growth | Demain et.al [11] |
II-2 | M | 1 | 11 | Severe to profound | CI + HA | NA | NA | Tightness in the muscles of his lower limbs | Problems with tooth growth | |||||
Family 9 | Proband | North American | c.72C > A p.Cys24Stop | c.1439G > A p.Arg480His | M | 1.5 | 4 | Profound | Not recorded | NA | NA | NO | NO | Demain et.al [11] |
Family 10 | II-1 | Chinese Han | c.349G > A p.Asp117Asn | c.908 T > C p.Leu303Pro | M | 2.5 | 7 | Profound | HA + Right CI | NA | NA | NO | NO | This study |
II-2 | M | 1 | 10 | Severe to profound | HA + CI | NA | NA | NO | NO | |||||