Table 1 Clinical data for three patients with novel LHX3 mutations
Patient 1 (II:2, Family 1) | Patient 2 (II:2, Family 2) | Patient 3 (II:4, Family 2) | |
|---|---|---|---|
Age, years | 7 | 11 | 2 |
Gestational age, weeks | 39 | 39 | 39 |
Birth weight, kg (SD) | 3.2 (0SD) | 3 (− 0.7SD) | 2.9 (− 0.7SD) |
Birth length, cm (SD) | 45 (−2.5SD) | NA | 46 (−1.8SD) |
Age of onset, months | 3 | 2 | 2 |
Initial manifestation hypopituitarism | + | + | + |
Basal GH μg/L (>10) | <0.2 | <0.5 | <0.5 |
TSH mU/L (0.27–4.2) | 0.02 | 0.04 | 0.4 |
PRL μg/L (2.5–15) | 0.1 | 0.1 | NA |
LH U/L (0.1–3.3) | <0.1 | <0.1 | <0.1 |
FSH U/L (0.1–7) | <0.1 | <0.1 | <0.1 |
ACTH ng/L (5–60) | 6 | 8 | 16 |
cortisol nmol/L (190–750) | 70 | 62 | 102 |
FT4 pmol/L (12–22) | 4.4 | 9.3 | 10.3 |
IGF1 ng/L (115–498) | <25 | <25 | NA |
IGFBP3 mg/L (0.7–3.6) | <0.5 | <0.3 | NA |
Hypolplastic pituitary gland | + | + | - |
Limited neck rotation | + | + | - |
SNHL | + | + | + |
Developmental delay (Mild) | + | + | + |
Other findings | Dolichocephaly, Hypolasia of facial bones, frontal bossing, short webbed neck | Dolichocephaly, Thoracic scoliosis, squint | None |
Mutation Identified | c.437G > T (p. Cys146Phe) Homozygous | c.466C > T (p. Arg156Ter) Homozygous | |
Type of mutation | Missense mutation | Nonsense | |
Effect on protein | Location a well-established domain | Null mutation | |
Computation (in silico) predictive analysis | “Damaging” | “Damaging” | |
Population data | Not annotated as polymorphism | Not annotated as polymorphism | |
Functional data | Located in functional domain | Located in functional domain | |
Allelic and family segregation data | Recessive mutation and strong segregation | Recessive mutation and strong segregation | |
Other Evidence | Relevant to patient’s phenotype | Relevant to patient’s phenotype | |
Variant classification (ACMG) | Likely pathogenic | Pathogenic | |