A Case Report and Literature Review of a Novel Mutation in the MAGED2 Gene of a Patient With Severe Transient Polyhydramnios

Background: Polyhydramnios occurs frequently during pregnancy. Mutations in the MAGED2 gene can cause X-linked acute early-onset polyhydramnios with a severe but transient form of antenatal Bartter's syndrome.Case Presentation: Here, we report a new novel frameshift mutation c.733_734delCT (p. Leu245GlufsTer4) in the MAGED2 gene (NM_177433.1) that caused prenatal polyhydramnios, but did not cause polyuria after birth. Follow-up was conducted for 2 months, and the baby's growth and development were normal, without polyuria and renal impairment. In addition, we identified all individuals with MAGED2 mutations reported in the literature before March 2021.Conclusion: We report a new case with a novel variant of the MAGED2 gene that caused severe hydramnios but with a good result and summary clinical characteristics in a newborn with antenatal Bartter's syndrome caused by an MAGED2 mutation. Good prenatal diagnosis and genetic consultation can improve pregnancy monitoring and newborn management.

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A novel MAGED2 variant in a Chinese preterm newborn with transient antenatal Bartter’s syndrome with 4 years follow-up

BMC Nephrology ◽

10.1186/s12882-021-02553-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Mingsheng Ma ◽

Mengqi Zhang ◽

Yu Zhou ◽

Fengxia Yao ◽

Min Wei ◽

...

Keyword(s):

Clinical Symptoms ◽

Early Recognition ◽

Male Infant ◽

Bartter’S Syndrome ◽

Bartter's Syndrome ◽

Renal Tubular Disorder ◽

Novel Variant ◽

Renal Tubular ◽

Antenatal Bartter’S Syndrome

Abstract Background Transient antenatal Bartter’s syndrome caused by MAGED2 mutation is a rare X-linked recessive renal tubular disorder. Cases reported are mostly infants, and the long-term prognosis of the disease is still under investigation. Case presentation We encountered a preterm male infant with polyhydramnios, polyuria, salt loss, hypercalciuria, nephrocalcinosis and alkalosis. Antenatal Bartter’s syndrome was suspected, but these clinical symptoms surprisingly disappeared after about 2 months. This led to the clinical diagnosis of transient antenatal Bartter’s syndrome. Gene analysis in this patient disclosed a novel variant (c.1598C > T, p.Ala533Val) in exon 12 of MAGED2 gene, and his mother was a heterozygous carrier. This patient was followed up in clinic for 4 years without recurrence of imbalance of potassium, sodium and chloride. His height and weight were in normal range, and all laboratory examinations and nephrotic ultrasound were also normal. Conclusions We reported the first Chinese case of transient antenatal Bartter’s syndrome caused by MAGED2 mutation. The 4-year follow-up of our case further demonstrates the benign prognosis of the disease and indicates that early recognition of this phenotype could avoid unnecessary treatments.

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The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0030 ◽

2020 ◽

Vol 33 (12) ◽

pp. 1605-1608

Author(s):

Xiao Qin ◽

Jingzi Zhong ◽

Dan Lan

Keyword(s):

Diabetes Mellitus ◽

Novel Mutation ◽

Male Infant ◽

Neonatal Diabetes ◽

Monogenic Diabetes ◽

Neonatal Diabetes Mellitus ◽

Rare Form ◽

Case Presentation ◽

Abcc8 Gene

AbstractObjectivesNeonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes that is usually diagnosed in the first six months of life.Case presentationWe report on a male infant with neonatal diabetes who presented with diabetic ketoacidosis at two months and 16 days. A novel homozygous missense mutation (c.259T>G) was identified in the ABCC8 gene. In this case, insulin was replaced with glimepiride at a dosage of 0.49 mg/kg/day at five months, and this achieved metabolic control and satisfactory growth as observed at follow-up.ConclusionsThis report improves our understanding of the mutational spectrum of ABCC8, which is normally associated with NDM, and shows that the treatment regimen for this condition can be successfully switched from insulin therapy to the use of sulfonylurea.

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A common NKCC2 mutation in Costa Rican Bartter's syndrome patients: evidence for a founder effect.

Journal of the American Society of Nephrology ◽

10.1681/asn.v8111706 ◽

1997 ◽

Vol 8 (11) ◽

pp. 1706-1711 ◽

Cited By ~ 3

Author(s):

C L Kurtz ◽

L Karolyi ◽

H W Seyberth ◽

M C Koch ◽

R Vargas ◽

...

Keyword(s):

Mutant Allele ◽

Common Ancestor ◽

Costa Rican ◽

Bartter’S Syndrome ◽

Bartter's Syndrome ◽

Renal Tubular Disorders ◽

Genes Encoding ◽

Renal Tubular ◽

Distinct Features ◽

Antenatal Bartter’S Syndrome

Bartter's syndrome involves an overlapping set of closely related renal tubular disorders that can be subdivided into at least three clinical phenotypes: (1) the hypercalciuric antenatal Bartter variant; (2) the classic Bartter variant; and (3) the hypocalciuric-hypomagnesemic Gitelman variant. Recent data demonstrate that in several phenotypically indistinguishable cohorts, antenatal Bartter's syndrome is genetically heterogeneous. In these patients, mutations in the genes encoding either the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the ATP-regulated potassium channel ROMK (KCNJI) have been identified. A cohort of 20 Costa Rican patients with a congenital syndrome that bears strong similarities to antenatal Bartter's syndrome but also has several distinct features has recently been described. In this cohort, we have identified a predominant mutation that introduces a premature stop in codon W625 of the NKCC2 gene (SCL12A1). This mutant allele is contained on a single common haplotype, suggesting that the majority of antenatal Bartter's syndrome patients in Costa Rica share a single common ancestor.

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Chronic renal failure in a boy with classic Bartter’s syndrome due to a novel mutation in CLCNKB coding for the chloride channel

European Journal of Pediatrics ◽

10.1007/s00431-008-0883-y ◽

2008 ◽

Vol 168 (9) ◽

pp. 1129-1133 ◽

Cited By ~ 3

Author(s):

Chien-Ming Lin ◽

Jeng-Daw Tsai ◽

Yi-Fen Lo ◽

Ming-Tso Yan ◽

Sung-Sen Yang ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Chloride Channel ◽

Novel Mutation ◽

Bartter’S Syndrome ◽

Bartter's Syndrome

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Clinical Characteristics And Identification of Novel TGF-β1 Mutation In Three Unrelated Chinese Families With Progressive Diaphyseal Dysplasia

10.21203/rs.3.rs-496094/v1 ◽

2021 ◽

Author(s):

Xiao-Hui Tao ◽

Xing-Guang Yang ◽

Zi-Yuan Wang ◽

Yang Xu ◽

Zhen-Lin Zhang ◽

...

Keyword(s):

Sanger Sequencing ◽

Clinical Characteristics ◽

Novel Mutation ◽

The Novel ◽

Chinese Families ◽

Progressive Diaphyseal Dysplasia ◽

Exon 4 ◽

Diaphyseal Dysplasia ◽

Tgf Β1

Abstract BackgroundTo investigate the clinical characteristics and molecular diagnosis of progressive diaphyseal dysplasia (PDD) in three unrelated Chinese families. MethodsThe present study recruited six patients aged 14 to 45 from three unrelated families with PDD, including five females and one male. Clinical manifestations, biochemical tests, radiographic examinations were analyzed and the TGF-β1 gene mutation was further identified by Sanger sequencing. In addition, data of treatment and follow-up were also collected.ResultsThe onset age of the patients ranged from 1 to 6 years. All the affected patients had family histories and were consisted with autosomal dominant inheritance pattern. All of them exhibited gait disturbance, fatigue, progressive bone pain, as well as muscle atrophy and weakness in limbs. Notably, there was one 15-year-old girl who experienced heart valve defects and tachycardia at birth. Laboratory examinations revealed the inflammatory markers were in high level, besides the extremely increased bone metabolism indicators. The thickened diaphysis of long bones and the narrowed medullary cavity were observed by radiography. Furthermore, radionuclide bone scan detected abnormal symmetrical radioactive concentration in the affected regions of bone. Sanger sequencing identified a missense heterozygous mutation in exon 4 of TGF-β1 gene, resulting in R218C, which confirmed PDD eventually. More important, a novel mutation c.669C>G in exon 4 of TGF-β1 gene harboring C223W were detected in family 3. Subsequent bioinformatics software predicted that the novel mutation was pathogenic. Our study also showed that zoledronic acid was not effective in the control of bone turnover markers and the relief of bone pain in patients with PDD.ConclusionIn addition to the typical PDD manifestations, the new phenotypic characteristics such as tachycardia and heart valve defect were firstly reported in one female patient carried the novel mutation p.Cys223Trp in TGF-β1 gene. In addition, our study indicated that the increased bone metabolism indicators and inflammatory markers may possess auxiliary diagnosis for PDD. More importantly, zoledronic acid was used to treat PDD patients in this study. After one-year follow-up, it was proved that the drug effect was not satisfactory, and new drugs need to be developed to treat the disease.

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A Rare Case Report of Acquired Bartters With Positive Anti Scl70 Antibody

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.212 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A106-A106

Author(s):

Arunkumar Ramanarth Pande ◽

Deepali Mohanty

Keyword(s):

Systemic Sclerosis ◽

Serum Cortisol ◽

Bartter Syndrome ◽

Age Group ◽

Bartter’S Syndrome ◽

Bartter's Syndrome ◽

Potassium Supplementation ◽

Renal Tubular ◽

Work Up

Abstract Introduction: Bartter syndrome autosomal recessive renal tubular disorders usualy presents in infant age group or antenatallyCase Description64 years housewife, a known case of hypothyroidism with in emergency with generalized weakness and hypotension. She had an small adrenal nodule work up which showed that it was non functional. On evaluation at time of stress (blood pressure 70/50) her serum cortisol was 300nmol/l and she was therefore started on hydrocortisone. Her records revealed hypokalemia for last 2 years. Workup of hypokalemia showed kaliuresis, metabolic alkalosis, hypercalciuria and excess chloride excretion in the urine, suggestive of bartter’s syndrome. But this needed further confirmation as bartter’s is rare in this age group and also the test was done at the time of stress. She was started on spironolactone and oral potassium supplementation. CECT head done for evaluation of postural dizziness showed chronic cortical venous thrombosis. On follow up ACTH stimulated cortisol was done which showed normal cortisol level so steroid was stopped. She was readmitted one month later with hypokalemia(K-1.8 meq/l) while being on same dosage of spironolactone and potassium. Workup of hypokalemia showed same feature of bartter’s syndrome. Considering the chain of events, a suggestion of bartter’s and response to steroid, a diagnosis of acquired autoimmune bartter’s syndrome along with hypothyroidism was made. An autoimmune work up showed anti SCL 70 positive2+(++). Patient responded to steroid, spironolactone, indomethacin and oral potassium supplementation. Discussion: Bartter’s syndrome can rarely happen in old age too. Seek for autoimmune cause once we suspect acquired bartter’s. To best of our knowledge previously only one case has been reported of acquired Bartter with systemic sclerosis. Patient may develop systemic sclerosis in future as anti SCL70 antibody is very specific for it. It is positive in less than 1 % of general population. Anti SCL70 antibody is rarely positive in Sjogrens syndrome. Our patient did not feature of sjogren or systemic sclerosis even after 4 years follow up

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