A novel <i>de novo</i> frameshift mutation in <i>NR0B1</i> and low prenatal estriol in adrenal hypoplasia congenita

Khattab, Ahmed; Nelson‐Williams, Carol; Cabreza, Vivienne; Macdonald, Anne; Loring, Erin; Saland, Jeffrey M.; New, Maria I.

doi:10.1111/nyas.13962

Cited by 2 publications

(1 citation statement)

References 15 publications

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“…The clinical findings of FGD is very diverse, also including subclinical hypothyroidism, characteristic facial features such as hypertelorism, medial epicanthus and frontal bossing, marginal gross motor developmental delay, gigantism and so on, except for symptoms due to glucocorticoid deficiency (10). Note, though that skin hyperpigmentation is familiar in PAI, absence of obvious hyperpigmentation can not rule out adrenal insufficiency (12). CAH often present with ambiguous or male-appearing external genitalia in girls, while the externalia of patients with AHC or FGD1 often present normal in the neonatal period (6,13).…”

Section: Diagnosis and Differential Diagnosis By Clinical Feature Andmentioning

confidence: 99%

Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected

Gao

Chen

2020

Front. Pediatr.

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Primary adrenocortical insufficiency (PAI) is an important cause of morbidity in neonates. The most common cause of PAI in neonates is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). Other rarer monogenic cases, for example, adrenal hypoplasia congenita (AHC) or familial glucocorticoid deficiency, also simulate clinical manifestation of 21-OHD, leading to misdiagnosis. The therapies and prognosis of these monogenic cases of PAI are entirely different. This study aimed to compare the differences of clinical data and identify genetic etiologies of PAI cases in the neonatal period. All 7 neonates initially presented with hyperpigmentation, hyponatremia, hyperkalemia, and high serum adrenocorticotropic hormone levels. Only CAH patients showed hyperandrogenism and remarkably elevated serum 17-hydroxyprogesterone levels. All the pathogenic mutations found in CYP21A2 were well known, except c.1069C>T (exon 8). The male patient with AHC had a novel hemizygous deletion of exon 2 in DAX1. The other one with familial glucocorticoid deficiency type 1 had two novel heterozygous mutations in the gene coding melanocortin 2 receptor, c.701C>T (exon 2) and c.119delT (exon 2). Glucocorticoid and/or mineralocorticoid replacement therapy depends on the cause of PAI. Genetic testing can be performed as a alternative diagnostic approach to provide information about therapy, prognosis, and genetic counseling.

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Section: Diagnosis and Differential Diagnosis By Clinical Feature Andmentioning

confidence: 99%

Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected

Gao

Chen

2020

Front. Pediatr.

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Novel non-stop variant of the NR0B1 gene in two siblings with adrenal hypoplasia congenita

Ota

Katsumata

Naiki

et al. 2022

Journal of Pediatric Endocrinology and Metabolism

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Objectives Mutations in the dosage-sensitive sex reversal-AHC critical region on the X chromosome, gene 1 (DAX-1, officially NR0B1), cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). Salt-losing adrenal insufficiency usually occurs during the neonatal period or early childhood. We report a novel non-stop variant of NR0B1 in two siblings and their unusual clinical course. Case presentation The proband was a boy who presented with an unusual form of AHC with neonatal onset of growth failure and mild salt loss, but without cutaneous pigmentation or plasma ACTH elevation. His 4-year-old elder brother had been growing healthily, but carried an AHC diagnosis. A non-stop variant of NR0B1 (p.*471K) was demonstrated in the patients and their mother. Conclusions We identified a novel non-stop variant of NR0B1 in two siblings. Mild salt loss associated with hyperkalemia is a crucial diagnostic clue for AHC, even without apparent symptoms of glucocorticoid deficiency.

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A novel de novo frameshift mutation in NR0B1 and low prenatal estriol in adrenal hypoplasia congenita

Cited by 2 publications

References 15 publications

Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected

Primary Adrenocortical Insufficiency Case Series in the Neonatal Period: Genetic Etiologies Are More Common Than Expected

Novel non-stop variant of the NR0B1 gene in two siblings with adrenal hypoplasia congenita

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