Clinical and auxological details for the probands with the novel GHR variants.
| Features . | Proband 1 . | Proband 2 . |
|---|---|---|
| GHR genetic variant | c.876-15T > G (rs199960137) | c.902T > G, p.V301G |
| Age at presentation (years) | 16.5 | 14.6 |
| Height at presentation, cm (SDS) | 153 (−3.2) | 155 (−2.7) |
| Bone age | 18 years G + P (CA 16.5yrs) | ND |
| Birth weight, g (SDS) | 2580 (−2.4) | 3650 (0.2) |
| BMI SDS | 0.6 | −1.5 |
| Basal GH µg/L | 0.4 | 0.7 |
| Peak GH µg/La | ND | 57.5 |
| IGF-1 ng/mL (SDS) | 345 (1.0) | <25 (−3.0) |
| GHBP IFMA pM (adult reference interval: 536-3634 pM) | 1666 | 14 567 |
| GHBP LIFA pM (adult reference interval: 154-1073 pM) | 467 | 3366 |
| Clinical phenotype | Relative macrocephaly, disproportionate short stature borderline mesomelic shortening on skeletal survey | No dysmorphic features |
| In silico predictions | CADD <10%, Gnomad Allele Frequency 0.03% | SIFT: Damaging, CADD 27.7 PolyPhen2:Probably Damaging, Not listed on Gnomad (novel) |
| Features . | Proband 1 . | Proband 2 . |
|---|---|---|
| GHR genetic variant | c.876-15T > G (rs199960137) | c.902T > G, p.V301G |
| Age at presentation (years) | 16.5 | 14.6 |
| Height at presentation, cm (SDS) | 153 (−3.2) | 155 (−2.7) |
| Bone age | 18 years G + P (CA 16.5yrs) | ND |
| Birth weight, g (SDS) | 2580 (−2.4) | 3650 (0.2) |
| BMI SDS | 0.6 | −1.5 |
| Basal GH µg/L | 0.4 | 0.7 |
| Peak GH µg/La | ND | 57.5 |
| IGF-1 ng/mL (SDS) | 345 (1.0) | <25 (−3.0) |
| GHBP IFMA pM (adult reference interval: 536-3634 pM) | 1666 | 14 567 |
| GHBP LIFA pM (adult reference interval: 154-1073 pM) | 467 | 3366 |
| Clinical phenotype | Relative macrocephaly, disproportionate short stature borderline mesomelic shortening on skeletal survey | No dysmorphic features |
| In silico predictions | CADD <10%, Gnomad Allele Frequency 0.03% | SIFT: Damaging, CADD 27.7 PolyPhen2:Probably Damaging, Not listed on Gnomad (novel) |
Glucagon stimulation, GH provocation testing (normal GH peak ≥7 ng/mL).
Abbreviations: BMI, body mass index; BWSDS, birth weight SD score; CA, chronological age; CADD, combined annotation dependent depletion; G + P, Greulich and Pyle bone age assessment utilizes a standard bone age atlas to estimate the bone age; GHBP, growth hormone binding protein; GHR, growth hormone receptor; GnomAD, Genome Aggregation Database; HSDS, height SD score; IFMA, immunofluorometric assay (total GHBP measurement); IGF1, insulin-like growth factor-I; LIFA, ligand immunofunctional assay (measurement of GHBP which can bind recombinant GH ie, “normal” extracellular domains); ND, not documented; SIFT, sorting intolerant from tolerant; SDS, SD score.
CADD score of 20 means the variant is amongst the top 1% of deleterious variants in the human genome but CADD has limited clinical validity for intronic variants.
Clinical and auxological details for the probands with the novel GHR variants.
| Features . | Proband 1 . | Proband 2 . |
|---|---|---|
| GHR genetic variant | c.876-15T > G (rs199960137) | c.902T > G, p.V301G |
| Age at presentation (years) | 16.5 | 14.6 |
| Height at presentation, cm (SDS) | 153 (−3.2) | 155 (−2.7) |
| Bone age | 18 years G + P (CA 16.5yrs) | ND |
| Birth weight, g (SDS) | 2580 (−2.4) | 3650 (0.2) |
| BMI SDS | 0.6 | −1.5 |
| Basal GH µg/L | 0.4 | 0.7 |
| Peak GH µg/La | ND | 57.5 |
| IGF-1 ng/mL (SDS) | 345 (1.0) | <25 (−3.0) |
| GHBP IFMA pM (adult reference interval: 536-3634 pM) | 1666 | 14 567 |
| GHBP LIFA pM (adult reference interval: 154-1073 pM) | 467 | 3366 |
| Clinical phenotype | Relative macrocephaly, disproportionate short stature borderline mesomelic shortening on skeletal survey | No dysmorphic features |
| In silico predictions | CADD <10%, Gnomad Allele Frequency 0.03% | SIFT: Damaging, CADD 27.7 PolyPhen2:Probably Damaging, Not listed on Gnomad (novel) |
| Features . | Proband 1 . | Proband 2 . |
|---|---|---|
| GHR genetic variant | c.876-15T > G (rs199960137) | c.902T > G, p.V301G |
| Age at presentation (years) | 16.5 | 14.6 |
| Height at presentation, cm (SDS) | 153 (−3.2) | 155 (−2.7) |
| Bone age | 18 years G + P (CA 16.5yrs) | ND |
| Birth weight, g (SDS) | 2580 (−2.4) | 3650 (0.2) |
| BMI SDS | 0.6 | −1.5 |
| Basal GH µg/L | 0.4 | 0.7 |
| Peak GH µg/La | ND | 57.5 |
| IGF-1 ng/mL (SDS) | 345 (1.0) | <25 (−3.0) |
| GHBP IFMA pM (adult reference interval: 536-3634 pM) | 1666 | 14 567 |
| GHBP LIFA pM (adult reference interval: 154-1073 pM) | 467 | 3366 |
| Clinical phenotype | Relative macrocephaly, disproportionate short stature borderline mesomelic shortening on skeletal survey | No dysmorphic features |
| In silico predictions | CADD <10%, Gnomad Allele Frequency 0.03% | SIFT: Damaging, CADD 27.7 PolyPhen2:Probably Damaging, Not listed on Gnomad (novel) |
Glucagon stimulation, GH provocation testing (normal GH peak ≥7 ng/mL).
Abbreviations: BMI, body mass index; BWSDS, birth weight SD score; CA, chronological age; CADD, combined annotation dependent depletion; G + P, Greulich and Pyle bone age assessment utilizes a standard bone age atlas to estimate the bone age; GHBP, growth hormone binding protein; GHR, growth hormone receptor; GnomAD, Genome Aggregation Database; HSDS, height SD score; IFMA, immunofluorometric assay (total GHBP measurement); IGF1, insulin-like growth factor-I; LIFA, ligand immunofunctional assay (measurement of GHBP which can bind recombinant GH ie, “normal” extracellular domains); ND, not documented; SIFT, sorting intolerant from tolerant; SDS, SD score.
CADD score of 20 means the variant is amongst the top 1% of deleterious variants in the human genome but CADD has limited clinical validity for intronic variants.
This PDF is available to Subscribers Only
View Article Abstract & Purchase OptionsFor full access to this pdf, sign in to an existing account, or purchase an annual subscription.
