Short Limbs Research Articles

Proximal femoral focal deficiency \u2013 a rare congenital entity: two case reports and a review of the literature

BackgroundProximal femoral focal deficiency is an extremely rare congenital anomaly with an incidence of 1.1–2.0 in 100,000 live births. It is a dysplastic phenomenon with predilections for the proximal two-thirds of the femur leading to limb length discrepancies.We report two cases of proximal femoral focal deficiency, which is a rare entity.Case presentationsCase 1A 4.5-month-old baby Annang tribe girl was referred in April 2019 to our Radiology Department, University of Uyo Teaching Hospital, Nigeria for lower limb radiographs. This was on account of her shortened left lower limb from birth despite uneventful antenatal history. An examination revealed bulky left thigh with abduction of her left hip joint.Radiographic evaluations showed absent left femoral capital epiphysis, with deficient proximal left femur. A diagnosis of proximal femoral focal deficiency was made. Sadly, the parents and baby failed to honor future orthopedic consultations on intimation of sequential management protocols.Case 2A 4-month-old baby Ibibio tribe girl was similarly referred in August 2019 to the same Radiology Department for lower limb conventional radiographs due to short left lower limb that was noticed from birth. An examination showed shortened left lower limb in external rotation. Her right and left lower limbs measured 27 cm and 23 cm, respectively, with landmark taken from anterior superior iliac spine to tip of medial malleolus. A diagnosis of proximal femoral focal deficiency was made. Corroborating radiographs showed shortened and hypoplastic left femoral shaft but preserved femoral capital epiphysis. Coincidentally, the parents have not brought back their baby to our orthopedic clinic.ConclusionsThe discovery of two cases of proximal femoral focal deficiency, a rare entity, from referrals for conventional radiography in our Radiology Department encourages literature documentation. Such recognition will facilitate early institution of management, thus ensuring meaningful childhood growth.

Diagnosis of Achondroplasia at Birth: A Case Report

Autosomal dominant mutations in fibroblast growth factor receptor 3 cause achondroplasia, the most common form of dwarfism in humans. Achondroplasia is a genetic disorder causing rhizomelic shortening of limbs. Head is often large with prominent forehead causing vaginal delivery difficult. A twenty-one years old multipara mother gave birth to a baby with achondroplasia via spontaneous vaginal delivery with episiotomy without any complication. Achondroplasia, in this case, was diagnosed on the basis of antenatal ultrasonography finding, clinical features and radiological finding of the baby. He was admitted in the special baby care unit for observation and discharged on the next day as no complications were noted. Keywords: achondroplasia; dwarfism; ultrasonography.

A Evaluation of Initial Treatment of Trochanteric Fractures using Gamma Nails

Background: Trochanteric fractures are extra-joint fractures, account for 55% of femoral proximal fractures. They often happen in the elderly with increased frequency due to age. Treatment experiences at 7A Military Hospital showed increased trochanteric fracture cases. To properly assess treatment effectiveness and select proper treatment methods, the study of “Evaluation of initial treatment of trochanteric fractures using gamma nails at 7A Military Hospital and made the conclusions of indications and applied techniques” was carried out.
 The study objectives are evaluating the initial treatment of trochanteric fractures using gamma nails at 7A Military Hospital and made the conclusions of indications and applied techniques.
 Methods and findings: nineteen patients diagnosed with traumatic trochanteric fractures and surgically treated with Gamma nails were monitored and evaluated for bone fusion, bone union, range of motion, limb shortening, and functional rehabilitation according to Merle D'Aubigné scale.
 Fourteen patients (82.35%) achieved proper bone union with the femoral neck-shaft angle of 1250 - 1300, three patients (17.65%) got slightly deviated bone union. Amongst patients aged under 60, 14/17 cases (82.35%) achieved “good” and “very good” functional rehabilitation, scored over 15 points according to Merle D΄aubigne Index; 3/17 cases (17.65%) got “average” recovery. Hip range of motion in 14 cases (82.35%) achieved “very good” (normal movement) or “good” (over 10% movement limitation) outcome, 3 cases had “average” movement (17.65%). Limb shortening of below 1cm took place in 10 patients (58.82%), 1 – 2 cm in 4 patients (23,53%) and over 3 cm in 3 patients (17.65%).
 Conclusions: The surgical treatment of trochanteric fractures using gamma nails yielded positive outcomes.
 Keywords: Gamma nails, trochanteric fractures, elderly, extra-joint.

Skeletal ciliopathies: a pattern recognition approach.

Ciliopathy encompasses a diverse group of autosomal recessive genetic disorders caused by mutations in genes coding for components of the primary cilia. Skeletal ciliopathy forms a subset of ciliopathies characterized by distinctive skeletal changes. Common skeletal ciliopathies include Jeune asphyxiating thoracic dysplasia, Ellis-van Creveld syndrome, Sensenbrenner syndrome, and short-rib polydactyly syndromes. These disorders share common clinical and radiological features. The clinical hallmarks comprise thoracic hypoplasia with respiratory failure, body disproportion with a normal trunk length and short limbs, and severely short digits occasionally accompanied by polydactyly. Reflecting the clinical features, the radiological hallmarks consist of a narrow thorax caused by extremely short ribs, normal or only mildly affected spine, shortening of the tubular bones, and severe brachydactyly with or without polydactyly. Other radiological clues include trident ilia/pelvis and cone-shaped epiphysis. Skeletal ciliopathies are commonly associated with extraskeletal anomalies, such as progressive renal degeneration, liver disease, retinopathy, cardiac anomalies, and cerebellar abnormalities. In this article, we discuss the radiological pattern recognition approach to skeletal ciliopathies. We also describe the clinical and genetic features of skeletal ciliopathies that the radiologists should know for them to play an appropriate role in multidisciplinary care and scientific advancement of these complicated disorders.

Autogenous fibula graft and cannulated screw fixation to cephalic cut out after DHS fixation: a retrospective study

BackgroundThis study aimed to explore the effect of the treatment through autologous fibula graft and hollow needle fixation to treat femoral head cutting after dynamic hip screw (DHS) fixation.MethodsA total of 41 patients were admitted to the department of orthopedic trauma and received DHS fixation. Preoperative and postoperative harris score of hip function, limb shortening length and collodiaphysial angle between operation group (n = 11) and non-operation group (n = 13) were compared.ResultsThere was no difference between the two groups before surgery (P > 0.05). There was a difference between the preoperative and postoperative in the operation group (P < 0.05). The excellent and good rate of the hip function score in patients 6 months after the operation was 55.6%. In the operation group, the hip function score increased after surgery (P < 0.001). Except for two groups of patients before operation, there was a difference in the limb shortening length and collodiaphysial angle between the operation group and non-operation group in other time points after surgery (P < 0.001).ConclusionThe application of the autogenous fibula graft and hollow nail fixation was effective in treating femoral head cutting after DHS fixation, and patients’ subjective evaluation and objective indicators’ outcomes of follow up were satisfactory, which was worthy of clinical application.

Abnormal Newborn Screening Follow-up for Severe Combined Immunodeficiency in an Amish Cohort with Cartilage-Hair Hypoplasia

Cartilage-hair hypoplasia (CHH) is an autosomal recessive, short limb skeletal dysplasia with a variable immunologic phenotype. The spectrum of immune function ranges from clinically normal to severe combined immunodeficiency (SCID). Multiple studies have shown that abnormal immune parameters may not predict severe outcomes. Newborn screening (NBS) using T cell receptor excision circle (TREC) assay can now effectively identify infants with severe T cell deficiency who are at risk for SCID. NBS has allowed for cost-effective identification of patients with SCID and improved outcomes with hematopoietic stem cell transplant (HSCT). Ohio reports two abnormal TREC results: decreased and absent TREC. This study evaluated the laboratory and clinical differences in eight Amish patients with CHH with an abnormal TREC result on the NBS. There were four patients with absent TREC and four patients with decreased TREC. The absent TREC patients had lower CD3, CD4, naïve CD4, CD8 cells, and phytohemagglutinin (PHA)-induced lymphocyte proliferation. Three patients with absent TREC were diagnosed with SCID and two underwent successful HSCT. Patients with absent TREC experienced more CHH-related morbidity including anemia requiring transfusion, Hirschsprung's disease, and failure to thrive. No patients with decreased TREC required HSCT. Our study indicates that CHH patients with absent TREC tend to have more severe immunological and clinical phenotype than patients with decreased TREC. Confirmation of these trends in a larger group would guide providers and parents in a timely referral for HSCT, or cost-effective surveillance monitoring of children with a life-threatening illness.

Combined medial malleoplasty and Taylor Spatial Frame after a supramalleolar osteotomy in the treatment of ankle deformity in skeletally immature patients: A prospective study of a novel technique and the short-term results

Background: This study examined the effectiveness of the Taylor Spatial Frame (TSF) in the treatment of deformity and limb shortening caused by distal tibial physeal arrest and the effectiveness in maintaining alignment and stability by reconstruction of the medial malleolus and the medial collateral ligament using an autogenous iliac crest graft and attached sartorius muscle-tendon. Methods: Thirteen pediatric patients with angular deformity of the distal tibia were enrolled in this prospective study. The mean age was 8.3 yr (range, 6 to 12 yr). All patients had open fractures with skin loss. Ten patients had Salter-Harris type IV physeal fractures, while three had Salter-Harris type V physeal injury. All patients had a varus ankle deformity (range, 15 to 33 degrees) and limb shortening (range, 1.9-cm to 3.3-cm). All patients were treated by a supramalleolar osteotomy and TSF for deformity correction for limb-length equalization. The absent medial malleolus was treated by medial malleoplasty with a graft from the ipsilateral iliac crest. Results: The mean follow-up period was 30 mo. The mean preoperative shortening of the tibia in relation to the fibula was 2.6 cm (range, 1.9 cm to 3.3 cm). The length of the short tibia was restored in all patients, and correction of the ankle deformity and stability were restored with a satisfactory outcome. Conclusions: TSF is highly effective in the treatment of distal tibial deformity in pediatric patients due to traumatic physeal arrest. Reconstruction of the medial malleolus and its ligamentous attachment is crucial for ankle joint stability. Level of Evidence: Level IV.

One-anastomosis gastric bypass with a short limb

To develop an acceptable method of surgical treatment of patients with obesity grade 1 and 2 in accordance with the following criteria: high safety, no risk or minimal risk of intestinal malabsorption, no limitations for postoperative gastrointestinal examination, no need for organ resection and surgical reversibility in case of necessity. In accordance with the above-mentioned criteria, we have modified OAGB (one-anastomosis gastric bypass). A gastric tube was formed from a lesser curvature using 33Fr stomach catheter with a length of at least 25 cm. Manual retrogastric retrocolic anastomosis in «end-to-side» fashion was performed within 20 cm from the ligament of Treitz. This type of anastomosis made it possible to preserve gastric tube length as much as possible that reduces the risk of jejunogastroesophageal reflux. There were 16 patients (15 females and 1 male) aged 23-48 years for the period from June 2019 till March 2020. Mean weight of patients was 86.12 kg (range 62-124). Mean BMI was 35.15 kg/m2 (ranged 21.96-39.62). In 6 months after surgery, all patients achieved normal BMI. Man BMI dropped to 23.8 kg/m2. Minimal excessive weight loss was 81.8%, maximal excessive weight loss - 125%. Control esophagogastroduodenoscopy was performed in 5 patients after 6 months and later. During retrograde duodenoscopy, we visualized major duodenal papilla in all cases using a flexible endoscope with standard optic system. The proposed modification of one-anastomosis gastric bypass with a short limb is a safe and effective procedure in bariatric surgery. This surgery ensures postoperative diagnostic and therapeutic endoscopic procedures in all parts of stomach and duodenum. This method could be recommended for surgical treatment of patients with obesity grade 1 and 2 after additional clinical trials and analysis of long-term results.

Correlation of the lower limb anatomical shortening with scoliotic deformity of the spine

The article deals with the analysis of the correlation between the anatomical shortening of the lower limb and the formation of a scoliotic curve. Despite the fact that the subject matter lacks sufficient research, an attempt is made to consider the data of domestic and foreign scientific studies that shed light on the issue. Within the framework of data analysis in an independent study of a group of 47 patients with shortening of the lower limb combined with vertebral scoliotic deformity, 4 different types of compensatory deformities of the spine were determined. Variants of possible correction were suggested depending on the type and complexity of the deformity. The conducted study stresses the importance of further theoretical and practical development of the subject matter and improvement of therapeutic and preventive measures for scoliosis.

Clinical Practice Guidelines for Achondroplasia.

.Achondroplasia (ACH) is a skeletal dysplasia that presents with limb shortening, short stature, and characteristic facial configuration. ACH is caused by mutations of the FGFR3 gene, leading to constantly activated FGFR3 and activation of its downstream intracellular signaling pathway. This results in the suppression of chondrocyte differentiation and proliferation, which in turn impairs endochondral ossification and causes short-limb short stature. ACH also causes characteristic clinical symptoms, including foramen magnum narrowing, ventricular enlargement, sleep apnea, upper airway stenosis, otitis media, a narrow thorax, spinal canal stenosis, spinal kyphosis, and deformities of the lower extremities. Although outside Japan, papers on health supervision are available, they are based on reports and questionnaire survey results. Considering the scarcity of high levels of evidence and clinical guidelines for patients with ACH, clinical practical guidelines have been developed to assist both healthcare professionals and patients in making appropriate decisions in specific clinical situations. Eleven clinical questions were established and a systematic literature search was conducted using PubMed/MEDLINE. Evidence-based recommendations were developed, and the guidelines describe the recommendations related to the clinical management of ACH. We anticipate that these clinical practice guidelines for ACH will be useful for healthcare professionals and patients alike.

Anesthesia Management in an Acondroplasic Patient Developing Cardiac Tamponade Due to Myxedema

Skeletal dysplasia is a complex group of diseases that can occur with different clinical findings, and bone and cartilage tissue are affected. Various congenital malformations, spinal anomalies, limb shortenings and disproportionate length shortenings are seen in skeletal dysplasias, which can be divided into 40 main groups according to clinical, laboratory and radiological evaluations. In addition to bone anomalies, endocrinological problems such as hypoglycemia, hypothyroidism, hypocalcaemia, hypercalcemia, and adrenal insufficiency may occur. Achondroplasia is the most common type of skeletal dysplasia with autosomal dominant transition. There may be problems in anesthesia management due to limited neck extension, apnea and spinal anomalies. In this presentation, we aimed to present our general anesthesia experience in the female patient diagnosed with achondroplasia planned for pericardiocentesis due to cardiac tamponade in the light of the literature.

Opsismodysplasia and Dilated Cardiomyopathy: a case report

Background: Opsismodysplasia (OPSMD) is an extremely rare and severe autosomal recessive skeletal dysplasia that is under the category of severe spondylodysplastic dysplasia. It is characterized by delayed bone maturation, and affected patients are identified by a peculiar craniofacioskeletal dysmorphism in the form of wide anterior fontanelle, depressed nasal bridge, anteverted nares, and short limbs and feet. Radiologically, they are characterized by severe platyspondyly, squared metacarpals, delayed skeletal ossification, and metaphyseal cupping. Case Presentation: We present the clinical and radiological features of a 14-month-old boy with a homozygous, likely pathogenic variant in INPPL1 gene c.2627dup (p.Pro977Thrfs*7) consistent with the diagnosis of OPSMD. He also has dilated cardiomyopathy. Conclusion: OPSMD is an uncommon form of skeletal dysplasia that should be suspected in the context of short stature with characteristic radiological features. Up to now, no definitive therapeutic measures are available, and hence preventive measures are essential in the management of families with affected members.

Fitness Programs Features According to the Body Types of High School Girls

The Actuality of the Research. Fitness is one of the most innovative approaches in the establishment of the physical training programme, which is good for shaping the body and body mass. Fitness contributes to the harmonization of physical development and improves the functional statement of body’s system. In the contemporary scientific researches it is expected that theoretical-methodological basis of fitness integration in the school system of physical education will contribute to increasing of physical preparedness level and motivation to practice sports among the teenagers, their physical development, health promotion, socialization and self-determination. The Methods of the Research. The analysis of academic papers, questionnaire, testing, medical examination of students, pedagogical experiment; determination of the level of physical development and physical preparedness; mathematical statistics method. The study was conducted on the basis of the Lutsk Middle School of General Education I–III levels № 18, Lutsk Middle School of General Education I– III levels № 25, Lutsk Jurisprudential Lyceum of Heavy Physical Training. 120 high school girls were involved in the study. The Results of the Research. Different physical types were taken into account by developing fitness programs (asthenic, hypersthenic, normosthenic). The results of the study show that 22 % of high school girls are asthenic body type, 19 % are hypersthenic, 59 % of high school girls are normosthenic body type. The strength exercises to increase the body mass and improve the muscle tone are recommended for girls of asthenic body type with slight stature, above average height, narrow shoulders, thin limbs and underweight. The high school girls of hypersthenic body type are with a massive body, average height, broad shoulders, short limbs and they are overweight. Physical exercises for them were focused on decrease in weight of a body, the reduction of body types (shoulders, thorax, stomach, pelvis, hips), the reduction of adipose tissue. The high school girls of normosthenic body type have relatively proportional body. That is why the physical activities are aimed at improvement of muscle tone, slowdown of body mass and reduction of the pelvis. Висновки . Результати дослідження будуть застосовані до створення програми з метою підвищення фізичної активності та поліпшення функціональної та фізичної підготовленості для дівчат середньої школи.

Greater agility increases probability of survival in the endangered northern quoll.

Introduced predators combined with habitat loss and modification are threatening biodiversity worldwide, particularly the 'critical weight range' (CWR) mammals of Australia. In order to mitigate the impacts of invasive predators on native species in different landscapes, we must understand how the prey's morphology and performance determine their survival. Here, we evaluated how phenotypic traits related to escape performance predict the probability of survival for an endangered CWR mammal, the northern quoll (Dasyurus hallucatus). We measured mass, body size, body shape, body condition and age, as well as maximum sprint speed, acceleration and agility of female quolls over two consecutive years. Those with higher body condition and agility around a 135deg corner were more likely to survive their first 21 months of life but were not more likely to survive after this period. No other morphological or performance traits affected survival. Heavier second-year individuals were more agile than first years but second years experienced higher mortality rates throughout the year. Females with higher body condition and agility around a 135deg corner tended to have shorter limbs and feet but longer heads. Our findings suggest that higher body condition and agility are advantageous for survival in female northern quolls. These results can be used to develop predictive models of predator-prey interactions based on performance capacity and how performance is affected by habitat, aiding conservation efforts to predict and manage the impact of introduced predators on native species.

Schatzker Type VI Injury with Missed Posterior Dislocation of the Hip

ABSTRACT Introduction Posterior dislocation of the hip can be an associated injury with fracture neck and shaft of the femur fractures. Case description A 33-year-old male came to us with above knee slab of the left leg. He had a fall from the bike and took initial treatment elsewhere. The X-ray and diagnosis of Schatzker type VI injury of the left knee were already done in the previous hospital. The upper tibia fixed with L-plate with screws. When the patient started walking in parallel bar, he felt twisting strain on the left hip and complained of pain in the left hip region. Now, the patient had shortening and internal rotation of the left lower limb. Clinically diagnosed posterior dislocation of the left hip was confirmed with X-ray. Reduction of dislocation was done. Conclusion X-rays of proximal and distal joints are mandatory. The statement stands testimony every time. How to cite this article Mothilal M, Khader FA, Rajan TS, et al. Schatzker Type VI Injury with Missed Posterior Dislocation of the Hip. J Orth Joint Surg 2020;2(1):43–45.

Description of a minimally invasive technique with a modified instrument for the osteosynthesis of proximal femoral fractures using the standard DHS and case series

ABSTRACT Introduction: the number of hip fractures is estimated to increase from 1.66 million in 1990 to 6.26 million by 2050. Internal fixation is the most common surgical treatment for intertrochanteric fractures. Objectives: the objective of the present research is to describe a minimally invasive technique with a modified instrument for the treatment of stable proximal femoral trochanteric fractures using the standard DHS, classified as Tronzo types 1 and 2 (AO 31A1.2), and presenting a case series. Methods: a case was selected to present the technique. Patients operated by this technique undergo a clinical evaluation and preoperative preparation as routine. The criteria for inclusion in the study were the presence of stable fracture of the proximal femur verified by two hip specialist orthopedists, and operated by the minimally invasive technique with a modified instrument using a standard DHS. Exclusion criteria were cases of patients operated for unstable fractures, and the use of other surgical techniques. A case series of 98 patients was performed and discussed. Results: minimally invasive technique with a modified instrument using the standard DHS device can reduce bleeding, it decreases soft tissue injuries, surgical time, and hospital stay, as any other MIPO procedures. Ninety-eight patients underwent the operation (Tronzo types I and II), 59 female and 39 male, ages from 50 to 85 years old. Immediate post-operative complications were shortening of the lower limb, loss of fracture reduction, and death by clinical complications. Conclusion: the present study describes a minimally invasive surgical technique using a modified instrument to perform proximal femoral osteosynthesis for stable trochanteric fractures, using the standard DHS.

Description of the D4/D4 genotype in Miniature horses with dwarfism.

Four causative mutations (D1, D2, D3*, and D4) of chondrodysplastic dwarfism have been described in the equine aggrecan (ACAN) gene. Homozygotes for one of these mutations and heterozygotes for any combination of these mutations exhibit the disproportionate dwarfism phenotype. However, no case description of homozygotes for D4 (D4/D4) has been reported in the literature, to our knowledge. We report 2 Miniature horses with the genotype D4/D4 in the ACAN gene. Clinically, the 2 dwarfs had a domed head that was large compared to the rest of the body, mandibular prognathism, and short and bowed limbs, mainly in the proximal region of the metatarsal bones. Radiographic examination revealed contour irregularities of the subchondral bone in the long bones and confirmed mandibular prognathism; histopathology revealed irregular chondrocyte organization. To determine the genotypes of the horses, we performed DNA extraction from white blood cells, PCR, and Sanger sequencing. Genotyping demonstrated that these 2 animals had the D4/D4 genotype in the ACAN gene. The D4/D4 dwarfs were clinically similar to animals with the other ACAN genotypes reported for this disease. Identification of heterozygous animals makes mating selection possible and is the most important control measure to minimize economic losses and casualties.

The Question of Short Lower Limb and Long Lower in Manual Therapy: An Overview

The purpose of this paper is to review relevant literature concerning limb length inequalities in adults and to make recommendations for assessment and intervention based on the literature and our own clinical experience. The research was carried out on PUB MED, Non-English articles and duplicates in the databases were not included. Limb length inequality and common classification criteria are defined and etiological factors are present. Common methods of detecting limb length inequality include model manual technics. This work has the purpose of describing a well standardized therapeutic in the form of practical guidance. The approach we describe provides standardized model evaluation for leg lower limb in order to be used in rehabilitation clinic.

Unilateral Isolated Proximal Femoral Focal Deficiency in an Egyptian Infant and Review of Literature

AbstractProximal femoral focal deficiency (PFFD) is a rare congenital anomaly of the femur ranging from mild shortening to total agenesis. If left untreated, it could lead to impaired child growth, abnormal gait, vertebral abnormalities, cosmetic problems, and behavioral changes. We report on an Egyptian female, presenting to us at the age of 15 days with a short left lower limb. Both upper limbs and the right lower limb were normal and she was not dysmorphic. The skeletal survey showed an isolated short left femur. At the age of 11 months, clinical reexamination confirmed left femur shortening. Echocardiogram and abdominal sonography revealed no abnormality. Magnetic resonance imaging (MRI) of the pelvis and lower limbs revealed isolated left proximal femoral focal deficiency. Her developmental milestones were normal. She was referred to pediatric orthopaedics for early intervention and proper management. To our knowledge and after reviewing the literature, this patient represents the first case of unilateral isolated proximal focal femoral deficiency in Egypt. In conclusion, PFFD diagnosis needs a systemic skeletal–facial–genital phenotyping to differentiate from overlapping genetic disorders. Early diagnosis and radioimaging are highly important for proper management.

A novel NPR2 mutation (p.Arg388Gln) in a patient with acromesomelic dysplasia, type Maroteaux.

.Acromesomelic dysplasia, type Maroteaux (AMDM) is a congenital bone dysplasia characterized by disproportionate, acromesomelic shortening of the limbs and mild spondylar dysplasia. AMDM is caused by biallelic loss-of-function mutations in NPR2 encoding natriuretic peptide receptor-B. We report on a 25-yr-old Japanese woman with AMDM. Her height was 119.0 cm (–7.4 SD) and weight 35 kg (–2.3 SD). She had acromesomelic shortening of limbs and severe brachydactyly. Radiological examination showed that her metacarpals and phalanges were short and wide, and her vertebral bodies were mildly flattened. Molecular analysis revealed a novel homozygous NPR2 mutation (c.1163G>A, p.Arg388Gln). We performed in vitro functional studies using HA-tagged wild-type (WT) and Arg388Gln vectors (HA-WT-NPRB and HA-R388Q-NPRB). Cells expressing HA-R388Q-NPRB showed negligible cGMP responses to C-type natriuretic peptide (CNP) stimulation, indicating that the mutation led to severe loss-of-function. By immunofluorescence experiments under permeabilized conditions, HA-WT-NPRB was expressed on plasma membrane, while HA-R388Q-NPRB co-localized with an Endoplasmic Reticulum marker. Cells co-expressing R388Q and the WT exhibited lower responses under CNP treatment than cells co-expressing the WT and empty vectors. Thus, it was thought that R388Q caused a dominant-negative effect with a defect in cellular trafficking to the plasma membrane.