1 |
+; Family I |
GHR |
Splice |
Intron 6: c.619-1 G>C |
|
At 13 years old: 87.5cm (-8.5 SDS) and 12.4kg. Several hypoglycemic episodes. Late closure of fontanelles. Trunkal obesity, high-pitched voice, doll-like face, irregular hypoplastic teeth and small external genitalia. Absence of pubertal development. |
Saldanha and Toledo, 1981Saldanha PH and Toledo SP (1981) Familial dwarfism with high IR-GH: Report of two affected sibs with genetic and epidemiologic considerations. Hum Genet 59:367-372.
|
2 |
+; Family I |
GHR |
Splice |
Intron 6: c.619-1 G>C |
|
At 8 years old: 76cm (-9.4 SDS) and 10kg. Several hypoglycemic episodes. Late closure of fontanelles. Trunkal obesity, high-pitched voice, doll-like face, irregular hypoplastic teeth, small external genitalia and learning difficulties. |
Saldanha and Toledo, 1981Saldanha PH and Toledo SP (1981) Familial dwarfism with high IR-GH: Report of two affected sibs with genetic and epidemiologic considerations. Hum Genet 59:367-372.
|
3 |
+; Family II |
GHR |
Missense |
Exon 7: c.731 G>T |
p.S244I |
At 15.7 years old: 124cm (-6.1 SDS), 43.4 kg and BA=13.2 years. Weight at birth (full term) = 2 kg (< 3rd centile). GH=12mcg/L, IGF1 <18mcg/L, IGFBP3= 1.1mg/L. |
Jorge, et al., 2004Jorge AA, Souza SC, Arnhold IJ and Mendonca BB (2004) The first homozygous mutation (S226I) in the highly-conserved WSXWS-like motif of the GH receptor causing Laron syndrome: Supression of GH secretion by GnRH analogue therapy not restored by dihydrotestosterone administration. Clin Endocrinol 60:36-40.
|
4 |
?; Adopted; Family III |
GHR |
Nonsense |
Exon 5: c.338 dupA |
p.Y113X |
At 12 years old: 87.8cm (SDS) and 11.1kg. Length at birth = 44cm, and Weight= 3kg. Facial asymmetry, prominent forehead, depressed nasal bridge, short face, blue sclerae and microstomia. Severe dental crowding and high-pitched voice. Small penis (10th percentile). GH=26 mcg/L, IGF-1=22.5 ng/mL. |
Diniz et al., 2008Diniz ET, Jorge AA, Arnhold IJ, Rosenbloom AL and Bandeira F (2008) Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome. Arq Bras Endocrinol Metabol 52:1264-1271.
|
5 |
?; Family IV
|
GHR |
Splice |
Exon 6: c.594 A>G |
p.V199_M206del |
At 17.8 years old: 104.3cm (?7.8 SDS); GH =30mcg/L, GH peak =94mcg/L, IGF1 =23mcg/L, IGFBP3= 0.6mg/L. |
Jorge et al., 2005Diniz ET, Jorge AA, Arnhold IJ, Rosenbloom AL and Bandeira F (2008) Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome. Arq Bras Endocrinol Metabol 52:1264-1271.
|
6 |
+; Family V
|
GHR |
Splice |
Exon 6: c.594 A>G |
p.V199_M206del |
At 8.8 years old: 103.3cm (?5.0 SDS); GH 7.2mcg/L, GH peak 118mcg/L, IGF1 <18mcg/L. |
Jorge et al., 2005Diniz ET, Jorge AA, Arnhold IJ, Rosenbloom AL and Bandeira F (2008) Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome. Arq Bras Endocrinol Metabol 52:1264-1271.
|
7 |
?; Family VI
|
GHR |
Splice |
Exon 6: c.594 A>G |
p.V199_M206del |
At 11.3 years old: 113.8cm (-4.5 SDS); GH= 3.3mcg/L, GH peak= 36mcg/L, IGF1 <18mcg/L, IGFBP3= 0.6mg/L. |
Jorge et al., 2005Diniz ET, Jorge AA, Arnhold IJ, Rosenbloom AL and Bandeira F (2008) Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome. Arq Bras Endocrinol Metabol 52:1264-1271.
|
8 |
?; Family VI
|
GHR |
Splice |
Exon 6: c.594 A>G |
p.V199_M206del |
At 6.8 years old: 81cm (-7.6 SDS); IGF1 <18 mcg/L, IGFBP3= 0.4mg/L. |
Jorge et al., 2005Diniz ET, Jorge AA, Arnhold IJ, Rosenbloom AL and Bandeira F (2008) Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome. Arq Bras Endocrinol Metabol 52:1264-1271.
|
9 |
?; Family VII
|
GHR |
Splice |
Exon 6: c.594 A>G |
p.V199_M206del |
At 19.1 years old: 132cm (-6.4 SDS); GH 1.6mcg/L, GH peak= 38mcg/L, IGF1= 51mcg/L. |
Jorge et al., 2005Diniz ET, Jorge AA, Arnhold IJ, Rosenbloom AL and Bandeira F (2008) Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome. Arq Bras Endocrinol Metabol 52:1264-1271.
|
10 |
?; Family VII
|
GHR |
Splice |
Exon 6: c.594 A>G |
p.V199_M206del |
At 3.2 years old: 69cm (-7.4 SDS); GH peak =39mcg/L, IGF1 <18mcg/L. |
Jorge, et al., 2005Diniz ET, Jorge AA, Arnhold IJ, Rosenbloom AL and Bandeira F (2008) Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome. Arq Bras Endocrinol Metabol 52:1264-1271.
|
11 |
?; Family VIII |
GHR |
Splice |
Exon 6: c.594 A>G |
p.V199_M206del |
No data |
Gonçalves et al., 2014Goncalves FT, Fridman C, Pinto EM, Guevara-Aguirre J, Shevah O, Rosembloom AL, Hwa V, Cassorla F, Rosenfeld RG, Lins TS et al. (2014) The E180splice mutation in the GHR gene causing Laron syndrome: Witness of a Sephardic Jewish exodus from the Iberian Peninsula to the New World? Am J Medic Genet Part A 164a:1204-1208.
|
12 |
?; Family VIII |
GHR |
Splice |
Exon 6: c.594 A>G |
p.V199_M206del |
No data |
Gonçalves et al., 2014Goncalves FT, Fridman C, Pinto EM, Guevara-Aguirre J, Shevah O, Rosembloom AL, Hwa V, Cassorla F, Rosenfeld RG, Lins TS et al. (2014) The E180splice mutation in the GHR gene causing Laron syndrome: Witness of a Sephardic Jewish exodus from the Iberian Peninsula to the New World? Am J Medic Genet Part A 164a:1204-1208.
|
13 |
+; Family IX |
GHR |
Missense |
Exon 5 (GHR): c.409 G>A |
p.317N |
At 6 years old: 86cm (SDS), 10kg and BA= 3 years. Length at preterm birth (28 weeks) =39cm and Weight= 1.7kg. Mild dysmorphic features, atopic eczema, interstitial lung disease, hyperprolactinemia. GH peak =20.6mcg/L, IGF1=34ng/mL. Treatment with GH whithout clear improvement. |
Pugliese-Pires et al., 2010Pugliese-Pires PN, Tonelli CA, Dora JM, Silva PC, Czepielewski M, Simoni G, Arnhold IJ and Jorge AA (2010) A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings. Eur J Endocrinol 163:349-355.
|
|
|
STAT5B |
Frameshift |
Exon 5 (STAT5B): c.424_427 del |
p.L142fs X161 |
|
|
14 |
+; Family IX |
STAT5B |
Frameshift |
Exon 5: c.424_427 del |
p.L142fs X161 |
At 2 years old: 76cm (SDS), 7,5kg and BA=6.0 months. Length at preterm birth (33 weeks) = 49cm and Weight= 2.4kg. Prominent forehead, depressed nasal bridge and obesity with centripetal fat distribution. Atopic eczema, thrombocytopenic purpura, interstitial lung disease, hyperprolactinemia. |
Pugliese-Pires et al., 2010Pugliese-Pires PN, Tonelli CA, Dora JM, Silva PC, Czepielewski M, Simoni G, Arnhold IJ and Jorge AA (2010) A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings. Eur J Endocrinol 163:349-355.
|
|
|
|
|
|
|
GH peak =14.2mcg/L, IGF1 < 25ng/mL. Treatment with GH and IGF-1 whithout clear improvement |
|
15 |
+; Family X |
STAT5B |
Frameshift |
Exon 5: c.424_427 del |
p.L142fs X161 |
Deceased as a consequence of respiratory failure |
Scalco et al., 2017Scalco RC, Goncalves FT, Santos HC, Cardena M, Tonelli CA, Funari MFA, Aracava RM, Pereira AC, Fridman C and Jorge AAL (2017) Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: Evidence for a founder effect. Genet Mol Biol 40:436-441.
|
16 |
+; Family X |
STAT5B |
Frameshift |
Exon 5: c.424_427 del |
p.L142fs X161 |
Deceased as a consequence of respiratory failure |
Scalco et al., 2017Scalco RC, Goncalves FT, Santos HC, Cardena M, Tonelli CA, Funari MFA, Aracava RM, Pereira AC, Fridman C and Jorge AAL (2017) Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: Evidence for a founder effect. Genet Mol Biol 40:436-441.
|
17 |
+; Family XI |
GHR |
Misstart |
Exon 2: c.1A>T |
p.M1? |
At 4 years old: 80.2cm (??? SDS) and BA=2.0 years. Length at birth = 46cm and Weight= 3.450kg. Prominent forehead, depressed nasal bridge, high-pitched voice and delayed dentition. |
Present study |
GH peak>40.0mcg/L, IGF1=12.3ng/mL. |
|
|
|
|
|
|
|
18 |
+; Family XI |
GHR |
Misstart |
Exon 2: c.1A>T |
p.M1? |
At 2 years old: 73.2cm (SDS). Length at birth = 46cm and Weight= 3.400kg. Prominent forehead, depressed nasal bridge, high-pitched voice, sparse hair and late closure of fontanelles. GH =11.4mcg/L, IGF1=79ng/mL. |
Present study |