欢迎来到《四川大学学报(医学版)》

KLHL3新基因突变所致假性醛固酮减少症Ⅱ型1例报告

唐薇薇 马晚霞 孙世怡 冉兴无

唐薇薇, 马晚霞, 孙世怡, 等. 由KLHL3新基因突变所致假性醛固酮减少症Ⅱ型1例报告[J]. 四川大学学报(医学版), 2021, 52(5): 890-894. doi: 10.12182/20210960503
引用本文: 唐薇薇, 马晚霞, 孙世怡, 等. 由KLHL3新基因突变所致假性醛固酮减少症Ⅱ型1例报告[J]. 四川大学学报(医学版), 2021, 52(5): 890-894. doi: 10.12182/20210960503
TANG Wei-wei, MA Wan-xia, SUN Shi-yi, et al. A Case of Pseudohypoaldosteronism Type Ⅱ (PHA2) Caused by a Novel Mutation of KLHL3[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(5): 890-894. doi: 10.12182/20210960503
Citation: TANG Wei-wei, MA Wan-xia, SUN Shi-yi, et al. A Case of Pseudohypoaldosteronism Type Ⅱ (PHA2) Caused by a Novel Mutation of KLHL3[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(5): 890-894. doi: 10.12182/20210960503

KLHL3新基因突变所致假性醛固酮减少症Ⅱ型1例报告

doi: 10.12182/20210960503
基金项目: 四川大学华西医院学科卓越发展1·3·5工程项目(No. ZYGD18025)资助
详细信息
    通讯作者:

    E-mail:ranxingwu@163.com

A Case of Pseudohypoaldosteronism Type Ⅱ (PHA2) Caused by a Novel Mutation of KLHL3

More Information
  • 摘要: 患者,女,41岁,因“发现血钾升高18 d”入院。入院前18 d患者在外院住院期间查见血钾升高,予以对症处理,血钾正常后出院,因出院后反复血钾升高来我院就诊。患者有“急性肾炎”及“妊娠高血压”病史;入院半年前发现血压轻度升高未予干预。其父亲有“高血压、糖尿病”病史。入院后实验室检查发现患者具有高钾血症、高氯血症、代谢性酸中毒、血浆肾素水平低下但醛固酮水平正常等特点,基因检测发现KLHL3(Kelch like family member 3)基因出现一个c.1115delG新突变,从而确诊为假性醛固酮减少症Ⅱ型。给予间断性规律盐酸氢氯噻嗪口服治疗,患者血清电解质水平、血pH及BE、BEB恢复正常范围,随访12个月,患者无不适。
  • 图  1  住院期间血电解质测值

    Figure  1.  Serum electrolyte measurements of the patient during hospitalization

    图  2  患者KLHL3基因测序图及其参照序列

    Figure  2.  The KLHL3 gene sequencing map of the patient and its reference sequence

    The arrow refers to the mutation site. There was a homozygous pathogenic mutation in the KLHL3 gene of the patient. The mutation site was c.1115delG, a mutation caused by the deletion of G, resulting in a frame mutation, which was consistent with the autosomal recessive inheritance model and was diagnosed as pseudoaldosteronism type Ⅱ D.

    图  3  随访期间血电解质测值

    Figure  3.  Serum electrolyte measurements of the patient during the follow-up period

    表  1  患者卧立位肾素-血管紧张素Ⅱ-醛固酮水平

    Table  1.   The renin-angiotensin Ⅱ-aldosterone levels of the patient in supine and upright positions

    DatePRA/(ng/[mL·h])AT-Ⅱ/(ng/L)ALD/(ng/dL)ARR/(ng/dL∶ng/[mL·h])
    DecubitusStanding postureDecubitusStanding postureDecubitusStanding postureDecubitusStanding posture
    01-06 2.05 6.49 62.59 68.57 26.79 32.53 13.07 5.01
    01-09 0.14 0.22 39.08 44.44 10.95 9.52 78.21 43.27
    01-13 0.27 1.09 73.72 65.88 17.15 25.14 63.52 23.06
    01-20 0.30 54.32 18.92 63.07
     PRA: Plasma renin activity, decubitus reference value 0.05-0.79 ng/(mL·h), reference value of standing posture 0.93-6.56 ng/(mL·h); AT-Ⅱ: Angiotensin Ⅱ, decubitus reference value 28.2-52.2 ng/L, reference value of standing posture55.3-115.3 ng/L; ALD: Aldosterone, decubitus reference value 4.5-17.5 ng/dL, reference value of standing posture 9.8-27.5 ng/dL; ARR: Aldosterone to renin ratio; -: Not measured.
    下载: 导出CSV
  • [1] NAKANO K, KUBOTA Y, MORI T, et al. Familial cases of pseudohypoaldosteronism type Ⅱ harboring a novel mutation in the Cullin 3 gene. Nephrology (Carlton),2020,25(11): 818–821. doi: 10.1111/nep.13752
    [2] LLOUIS-DIT-PICARD H, KOURANTI I, RAFAEL C, et al. Mutation affecting the conserved acidic WNK1 motif causes inherited hyperkalemic hyperchloremic acidosis. J Clin Invest,2020,130(12): 6379–6394. doi: 10.1172/JCI94171
    [3] MABILLARD H, SAYER J A. The molecular genetics of Gordon syndrome. Genes (Basel),2019,10(12): 986. doi: 10.3390/genes10120986
    [4] PAVER W K, PAULINE G J. Hypertension and hyperpotassaemia without renal disease in a young male. Med J Aust,1964,2: 305–306. doi: 10.5694/j.1326-5377.1964.tb115766.x
    [5] GORDON R D, RAVENSCROFT P J, KLEMM S A, et al. A new Australian kindred with the syndrome of hypertension and hyperkalaemia has dysregulation of atrial natriuretic factor. J Hypertens Suppl,1988,6(4): S323–326. doi: 10.1097/00004872-198812040-00100
    [6] FUNDER J W, CAREY R M, MANTERO F, et al. The management of primary aldosteronism: Case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab,2016,101(5): 1889–1916. doi: 10.1210/jc.2015-4061
    [7] BOYDEN L M, CHOI M, CHOATE K A, et al. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature,2012,482(7383): 98–102. doi: 10.1038/nature10814
    [8] YANG Y, OU Y, REN Y, et al. Hypertension accompanied by hyperaldosteronism, hyperkalemia, and hyperchloremic acidosis: A case report and literature review. Case Rep Endocrinol,2020,2020: 1635413.
    [9] BATLLE D, ARRUDA J. Hyperkalemic forms of renal tubular acidosis: Clinical and pathophysiological aspects. Adv Chronic Kidney Dis,2018,25(4): 321–333. doi: 10.1053/j.ackd.2018.05.004
    [10] CASAS-ALBA D, VILA COTS J, MONFORT CARRETERO L, et al. Pseudohypoaldosteronism types Ⅰ and Ⅱ: Little more than a name in common. J Pediatr Endocrinol Metab,2017,30(5): 597–601. doi: 10.1515/jpem-2016-0467
    [11] MANSFIELD T A, SIMON D B, FARFEL Z, et al. Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type II, to chromosomes 1q31-42 and 17p11-q21. Nat Genet,1997,16(2): 202–205. doi: 10.1038/ng0697-202
    [12] RAFAEL C, SOUKASEUM C, BAUDRIE V, et al. Consequences of SPAK inactivation on hyperkalemic hypertension caused by WNK1 mutations: Evidence for differential roles of WNK1 and WNK4. Sci Rep,2018,8(1): 3249. doi: 10.1038/s41598-018-21405-x
    [13] LAI F, ORELLI B J, TILL B G, et al. Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene. Genomics,2000,66(1): 65–75. doi: 10.1006/geno.2000.6181
    [14] LOUIS-DIT-PICARD H, BARC J, TRUJILLANO D, et al. KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nat Genet,2012,44(4): 456–460, S1-3. doi: 10.1038/ng.2218
    [15] MORENO E, DE LOS HEROS P, PLATA C, et al. Structure-function relationships in the renal NaCl cotransporter (NCC). Curr Top Membr,2019,83: 177–204. doi: 10.1016/bs.ctm.2019.01.003
    [16] MURTHY M, KURZ T, O'SHAUGHNESSY K M. WNK signalling pathways in blood pressure regulation. Cell Mol Life Sci,2017,74(7): 1261–1280. doi: 10.1007/s00018-016-2402-z
    [17] LIN C M, CHENG C J, YANG S S, et al. Generation and analysis of a mouse model of pseudohypoaldosteronism type Ⅱ caused by KLHL3 mutation in BTB domain. FASEB J,2019,33(1): 1051–1061. doi: 10.1096/fj.201801023R
  • 加载中
图(3) / 表(1)
计量
  • 文章访问数:  69
  • HTML全文浏览量:  22
  • PDF下载量:  15
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-02-28
  • 修回日期:  2021-06-09
  • 网络出版日期:  2021-12-06
  • 刊出日期:  2021-09-20

目录

    /

    返回文章
    返回