Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome
Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome
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DOI：
10.1093/ndt/gfn689
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发表时间：
2009-05-01
影响因子：
6.1
通讯作者：
Vargas-Poussou, Rosa
中科院分区：
文献类型：
--
作者：
Brochard, Karine;Boyer, Olivia;Vargas-Poussou, Rosa
背景。早产儿/新生儿巴特综合征（BS）是一种遗传性失盐小管病，是由亨勒氏袢增厚升肢中参与NaCl重吸收的蛋白编码基因突变引起的。我们的目的是研究每种遗传亚型的频率、临床特征和预后。回顾性分析42例KCNJ1 （n = 19）、SLC12A1 （n = 13）、CLCNKB （n = 6）或BSND （n = 4）突变患儿的图表。中位随访时间为8.3年[0.4-18.0]年。我们描述了24个新突变：KCNJ1 10个，SLC12A1 11个，CLCNKB 3个。各组羊水过多的发病、出生月龄、身高、体重相似；3例患者无羊水过多或早产史，根据轻度肾钠消耗有CLCNKB突变。与这些数据相比，CLCNKB患者的钾（与KCNJ1相比P = 0.006，与SLC12A1相比P = 0.034）和氯离子血浆浓度最低（与KCNJ1相比P = 0.039，与SLC12A1相比P = 0.024），碳酸氢钠血症最高（与KCNJ1相比P = 0.026，与SLC12A1相比P = 0.014）。BSND突变患者诊断时耳聋不变；三分之二的KCNJ1突变患儿存在新生儿短暂性高钾血症。肾钙质沉着在KCNJ1和SLC12A1患者中是恒定的，而在BSND和CLCNKB患者中则没有。在大多数情况下，补充水/电解质+吲哚美辛导致追赶性生长。3例患者发生慢性肾衰竭：1例在20岁时发生KCNJ1突变，2例在出生后第一年发生CLCNKB和BSND突变，但未发生肾钙化症。我们在大量的早产儿/新生儿BS队列中证实，耳聋、一过性高钾血症和严重低钾血症低氯血症性碱中毒的分子研究分别针对BSND、KCNJ1和CLCNKB基因。慢性肾衰竭是一种罕见的事件，在该队列中与三种基因型相关，并不总是与肾钙质沉着症相关。
Background. Ante/neonatal Bartter syndrome (BS) is a hereditary salt-losing tubulopathy due to mutations in genes encoding proteins involved in NaCl reabsorption in the thick ascending limb of Henle's loop. Our aim was to study the frequency, clinical characteristics and outcome of each genetic subtype.Methods. Charts of 42 children with mutations in KCNJ1 (n = 19), SLC12A1 (n = 13) CLCNKB (n = 6) or BSND (n = 4) were retrospectively analysed. The median follow-up was 8.3 [0.4-18.0] years.Results. We describe 24 new mutations: 10 in KCNJ1, 11 in SLC12A1 and 3 in CLCNKB. The onset of polyhydramnios, birth term, height and weight were similar for all groups; three patients had no history of polyhydramnios or premature birth and had CLCNKB mutations according to a less severe renal sodium wasting. Contrasting with these data, patients with CLCNKB had the lowest potassium (P = 0.006 versus KCNJ1 and P = 0.034 versus SLC12A1) and chloride plasma concentrations (P = 0.039 versus KCNJ1 and P = 0.024 versus SLC12A1) and the highest bicarbonataemia (P = 0.026 versus KCNJ1 and P = 0.014 versus SLC12A1). Deafness at diagnosis was constant in patients with BSND mutations; transient neonatal hyperkalaemia was present in two-thirds of the children with KCNJ1 mutations. Nephrocalcinosis was constant in KCNJ1 and SLC12A1 but not in BSND and CLCNKB patients. In most cases, water/electrolyte supplementation + indomethacin led to catch-up growth. Three patients developed chronic renal failure: one with KCNJ1 mutations during the second decade of age and two with CLCNKB and BSND mutations and without nephrocalcinosis during the first year of life.Conclusions. We confirmed in a large cohort of ante/ neonatal BS that deafness, transient hyperkalaemia and severe hypokalaemic hypochloraemic alkalosis orientate molecular investigations to BSND, KCNJ1 and CLCNKB genes, respectively. Chronic renal failure is a rare event, associated in this cohort with three genotypes and not always associated with nephrocalcinosis.