Aldosterone synthase (CYP11B2) deficiency among Palestinian infants: Three novel variants and genetic heterogeneity

Yaniv Faingelernt, Eli Hershkovitz, Bassam Abu-Libdeh, Amal Abedrabbo, Sara Abu-Rmaileh Amro, Raz Zarivach, David Zangen, Eran Lavi, Alon Haim, Ruti Parvari, Abdulsalam Abu-Libdeh

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Aldosterone synthase deficiency (ASD) is a rare potentially life-threatening genetic disorder that usually presents during infancy due to pathogenic variants in the CYP11B2 gene. Knowledge about CYP11B2 variants in the Arab population is scarce. Here, we present and analyze five Palestinian patients and their different novel pathogenic variants. Data on clinical presentation, electrolytes, plasma renin activity, and steroid hormone levels of five patients diagnosed with ASD were summarized. Sequencing of the CYP11B2 gene exons was followed by evolutionary conservation analysis and structural modeling of the variants. All patients were from highly consanguineous Palestinian families. The patients presented at 1–4 months of age with recurrent vomiting, poor weight gain, hyponatremia, hyperkalemia, and low aldosterone levels. Genetic analysis of the CYP11B2 gene revealed three homozygous pathogenic variants: p.Ser344Profs*9, p.G452W in two patients from an extended family, and p.Q338stop. A previously described pathogenic variant was found in one patient: p.G288S. We described four different CYP11B2 gene pathogenic variants in a relatively small population. Our findings may contribute to the future early diagnosis and therapy for patients with ASD among Arab patients who present with failure to thrive and compatible electrolyte disturbances.

Original languageEnglish
Pages (from-to)1033-1038
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume185
Issue number4
DOIs
StatePublished - 1 Apr 2021

Keywords

  • CYP11B2
  • aldosterone synthase
  • failure to thrive
  • hyperkalemia
  • hyponatremia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'Aldosterone synthase (CYP11B2) deficiency among Palestinian infants: Three novel variants and genetic heterogeneity'. Together they form a unique fingerprint.

Cite this