Short Stature in a Patient with Cystic Fibrosis Caused by a 6.7-kb Human Growth Hormone Gene Deletion

Mullis, Primus-Eugen; Liechti‐Gallati, Sabina; Silvio, L. Di; Brook, C. G. D.; Paes-Alves, Auristela Freire

doi:10.1159/000182097

Cited by 9 publications

(7 citation statements)

References 9 publications

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“…37 Two studies did not report the dose of rhGH. 31,34 Baseline measures of height and weight were inconsistently reported among the observational studies, but all patients had deficient height and weight for their age. [31][32][33][34][35][36][37][38] Data Synthesis A summary of the results for all key questions of both qualitative and quantitative synthesis and strength of evidence is listed in Table 3.…”

Section: Single-arm Observational Studiesmentioning

confidence: 99%

“…Three were case reports, 31,37,38 of which 1 was of a patient with growth hormone deficiency and short stature, 31 1 was of a patient who had previously undergone lung transplantation, 37 and another was of 2 patients with CF-related liver dysfunction. 38 One study was funded by a foundation grant, 31 4 studies were funded by industry, 32-34,36 and 3 did not report their sources of funding. 35,37,38 The duration of treatment with rhGH ranged from 6 months to 3 years.…”

Section: Single-arm Observational Studiesmentioning

confidence: 99%

“…35,37,38 The duration of treatment with rhGH ranged from 6 months to 3 years. Ages of the patients in the studies ranged from 6 months to 13 years, [31][32][33][34][35][36]38 with the exception of 1 case report of a patient aged 18 years. 37 Doses of rhGH in the studies ranged from 0.16 to 0.35 mg/kg per week, 32,33,35,36,38 with the exception of 1 case report in which the dose was 2.2 mg/day.…”

Section: Single-arm Observational Studiesmentioning

confidence: 99%

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Recombinant Human Growth Hormone in the Treatment of Patients With Cystic Fibrosis

et al. 2010

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CONTEXT: Recombinant human growth hormone (rhGH) improves growth in patients with growth hormone deficiency or idiopathic short stature. Its role in patients with cystic fibrosis (CF) is unclear. OBJECTIVE:To review the effectiveness of rhGH in the treatment of patients with CF. METHODS:Medline and the Cochrane Central Register of Controlled Trials were searched from the earliest date through April 2010. Randomized controlled trials, observational studies, systematic reviews/ meta-analyses, or case reports were included if rhGH therapy was administered to patients with CF and data on prespecified harms, intermediate outcomes, or final health outcomes were reported. When applicable, end points were pooled by using a random-effects model. The overall body of evidence was graded for each outcome as insufficient, low, moderate, or high. RESULTS:Ten unique controlled trials (n ϭ 312) and 8 observational studies (n ϭ 58) were included. On quantitative synthesis of controlled trials, several markers of pulmonary function, anthropometrics, and bone mineralization were significantly improved versus control. Results of single-arm observational studies for the aforementioned outcomes were generally supportive of findings in clinical trials. There is insufficient evidence to determine the effect of rhGH on intravenous antibiotic use during therapy, pulmonary exacerbations, healthrelated quality-of-life, bone consequences, or total mortality, but moderate evidence suggests that rhGH therapy reduces the rate of hospitalization versus control.CONCLUSIONS: rhGH improved almost all intermediate measures of pulmonary function, height, and weight in patients with CF. Improvements in bone mineral content are also promising. However, with the exception of hospitalizations, the benefits on final health outcomes cannot be directly determined at this time.

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Section: Single-arm Observational Studiesmentioning

confidence: 99%

Section: Single-arm Observational Studiesmentioning

confidence: 99%

Section: Single-arm Observational Studiesmentioning

confidence: 99%

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Recombinant Human Growth Hormone in the Treatment of Patients With Cystic Fibrosis

et al. 2010

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“…A single Brazilian patient with a 6.7-kb GH gene deletion has been previously reported by Mullis et al (15). The patient developed growth-attenuating anti-GH antibodies after replacement therapy with GH of pituitary origin and also suffered from cystic fibrosis.…”

Section: Discussionmentioning

confidence: 85%

Clinical and molecuar characterization of Brazilian patients with growth hormone gene deletions

Arnhold

Osorio

Oliveira

et al. 1998

Braz J Med Biol Res

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Genomic DNA from 23 patients with isolated growth hormone (GH) deficiency (12 males and 11 females: heights -4.9 ± 1.4 SDS) was screened for GH gene deletions by restriction endonuclease analysis of polymerase chain reaction amplification products. Three unrelated patients had typical features of severe GH deficiency and deletions (6.7 kb in two and 7.6 kb in one) of the GH gene. The two patients with 6.7-kb deletions developed growth-attenuating anti-GH antibodies whereas the patient with the 7.6-kb deletion continued to grow with GH replacement therapy. Our finding that 3/23 (~13%) Brazilian subjects had GH gene deletions agrees with previous studies of severe isolated GH deficiency subjects in other populations. Two of three subjects (67%) with deletions developed blocking antibodies despite administration of exogenous GH at low doses. Interestingly, only 1/10 of cases with affected relatives or parental consanguinity had GH-1 gene deletions. Correspondence

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“…Amplification of specific DNA fragment in vitro using the polymerase chain reaction (PCR) requires a well controlled thermal cycling [1,2,3]. There are three stages in the PCR.…”

Section: Introductionmentioning

confidence: 99%

A new thermal cycling mechanism for effective polymerase chain reaction in microliter volumes

Lee

Tsai

Yuan

et al. 2004

Microsystem Technologies

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This study presents a new thermal cycler using infrared (IR) heating and water impingement cooling for polymerase chain reaction (PCR) amplification of 10 ll samples in thin glass capillary tubes. The thermal cycling system can achieve a temperature ramping-up rate of 65°C/s and a ramping-down rate of 80°C/s. Two other cooling mechanisms, natural convection and forced air convection, can also be used in the present system to obtain a ramping-down rate of 2°C/s and 6°C/s, respectively. The amplification of the 439 fragment of hepatitis B virus (HBV) DNA was successful. The PCR amplified products were analyzed by agarose gel electrophoresis with ethidium bromide staining for visualization. A comparison of results of the amplification products at three different ramping-down rates was made and the rapid thermal cycling of the present system can run DNA required amplification in 29 min for 20 thermal cycles that is only 1/3 the time spent in the conventional PCR machine used in comparison. IntroductionAmplification of specific DNA fragment in vitro using the polymerase chain reaction (PCR) requires a well controlled thermal cycling [1, 2, 3]. There are three stages in the PCR. The first stage is denaturation at which the sample is heated up from room temperature to denaturation temperature at approximately 90-95°C. The high temperature results in a separation of the double strands of DNA into two single stranded DNAs. The second stage is called annealing at which the sample temperature drops from the denaturation temperature to annealing temperature at approximately 40-65°C. At the annealing stage, added primers in the sample are paired with single stranded DNA through a Brownian motion in the solution and subsequent hydrogen-bonding. The final step is elongation (or extension) at which the sample temperature is heated up from the annealing temperature to the elongation temperature at approximately 72°C. Since the primers already have a strong ionic bonding to the DNA template on the specific locations at the annealing stage, dNTPs are added complementarily to the DNA template. A complete temperature cycle consists of the temperature variations in the three stages in PCR. To obtain enough yield of products, the number of temperature cycles required depends on the type of DNA for amplification.In a conventional PCR machine, thermal cycling is performed on a 10 ll sample in a microcentrifuge tube using a temperature controlled metal block. The major setback of this conventional thermal cycler is a long temperature lag in the sample behind the metal block. Consequently, amplification time for DNA products may usually take a few hours. To reduce the thermal cycling time, Wittwer and his co-workers constructed a rapid cycling system by introducing hot air to heat up the sample in thin capillary tubes [4]. In their system, the thermal cycling time for 20 cycles was reduced from 1-4 h in a metal block thermal cycler to 20 min. In addition, their system can obtain better specificity in amplification products with less transi...

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Short Stature in a Patient with Cystic Fibrosis Caused by a 6.7-kb Human Growth Hormone Gene Deletion

Cited by 9 publications

References 9 publications

Recombinant Human Growth Hormone in the Treatment of Patients With Cystic Fibrosis

Recombinant Human Growth Hormone in the Treatment of Patients With Cystic Fibrosis

Clinical and molecuar characterization of Brazilian patients with growth hormone gene deletions

A new thermal cycling mechanism for effective polymerase chain reaction in microliter volumes

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