Fernández-Lorenzo Ana E, Moreno-Álvarez Ana, Colon-Mejeras Cristóbal, Barros-Angueira Francisco, Solar-Boga Alfonso, Sirvent-Gómez Josep, Couce María L, Leis Rosaura
Department of Pediatrics, Hospital Teresa Herrera, Complejo Hospitalario Universitario A Coruña, A Coruña Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Service of Neonatology, Department of Pediatrics, Hospital Clínico Universitario de Santiago, CIBERER, Health Research Institute of Santiago de Compostela (IDIS) Unidad de Medicina Molecular-Fundación Pública Galega de Medicina Xenómica, Hospital Clínico Universitario Santiago de Compostela Unit of Pediatrics Gastroenterology, Hepatology and Nutrition, Pediatrics Department, Hospital Clínico Universitario de Santiago, Pediatrics Nutrition Group-IDIS, CiberObn Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
Medicine (Baltimore). 2018 Jul;97(28):e11397. doi: 10.1097/MD.0000000000011397.
The frequency of some Cystic Fibrosis (CF) Transmembrane Conductance Regulator gene (CFTR) mutations varies between populations. Genetic testing during newborn screening (NBS) for CF can identify less common mutations with low clinical expression in childhood and previously considered mild but not fully characterized, such as the mutation p.Val232Asp (c.695T > A). The aim of this study was to describe CF patients with the V232D mutation. We identify CF children with the V232D mutation detected by NBS and compare them with CF adults with this mutation whose diagnosis was prompted by clinical symptoms in the same period. We studied clinical, biochemical, spirometric, and prognostic features in both populations. NBS program tested 276,523 children during a period of 14 years (2003-2017) and identified 54 cases of CF. Six children (11%) had the V232D mutation. Over the same period, 5 adults (age 37.6 ± 16.29 years old) with symptoms of CF and this mutation were also diagnosed. Follow-up duration was mean 10.1 years for adults and mean 6.5 years for children. In the adult group, lung function was impaired at diagnosis in all patients (Forced Expiratory Volume1-FEV1-67.12% ± 13.09) and worsened in children tested during evolution (FEV1first: 113%; FEV1last: 64%). Pancreatic insufficiency was present in adult group, with recurrent pancreatitis in 1 present. Although with less clinical expression in children, V232D is associated with pulmonary and pancreatic involvement during adulthood and CF cannot be considered mild. This mutation is present in 11% of all patients diagnosed with CF in our region. Its inclusion in some NBS programs should be taken into account in order to improve the prognosis of affected children.
某些囊性纤维化（CF）跨膜传导调节因子基因（CFTR）突变的频率在不同人群中有所差异。在新生儿筛查（NBS）中进行的CF基因检测能够识别出在儿童期临床表达较低且以前被认为症状较轻但特征未完全明确的罕见突变，例如p.Val232Asp（c.695T＞A）突变。本研究的目的是描述携带V232D突变的CF患者。我们识别出通过NBS检测到携带V232D突变的CF儿童，并将他们与同期因临床症状而诊断出携带该突变的CF成人进行比较。我们研究了这两组人群的临床、生化、肺功能和预后特征。在14年期间（2003 - 2017年），NBS项目检测了276,523名儿童，共识别出54例CF患者。其中6名儿童（11%）携带V232D突变。在同一时期，还诊断出5名有CF症状且携带该突变的成人（年龄37.6±16.29岁）。成人的随访时间平均为10.1年，儿童平均为6.5年。在成人组中，所有患者在诊断时肺功能均受损（第1秒用力呼气容积 - FEV1 - 67.12%±13.09），在随访过程中接受检测的儿童肺功能恶化（首次FEV1：113%；末次FEV1：64%）。成人组存在胰腺功能不全，其中1例出现复发性胰腺炎。尽管V232D突变在儿童期临床表达较少，但在成年期与肺部和胰腺受累相关，CF不能被认为是轻症。该突变在我们地区所有诊断为CF的患者中占11%。为了改善患病儿童的预后，应考虑将其纳入一些NBS项目。
