Novel mutation in the nuclear receptor subfamily 0, group B, member 1 (NR0B1) gene associated with intrafamilial heterogeneity in three boys with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism from India

Mohan, Sony; Danda, Sumita; Mathai, Sarah; Simon, Anna

doi:10.4103/0970-258x.278692

Cited by 3 publications

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“…However, no well‐established genotype–phenotype relationship is known (Jadhav et al, 2011; Kyriakakis et al, 2017). In fact, pathogenic variants of the NR0B1 gene have been found in approximately 58% of males with primary adrenal insufficiency of unknown etiology (Mohan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

X‐linked congenital adrenal hypoplasia: Report of long clinical follow‐up and description of a new complex variant in the NR0B1 gene

Esquiaveto‐Aun,

de Mello,

Guaragna

et al. 2024

American J of Med Genetics Pt A

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Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype–phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment. At almost 4 years of age, the disorder was restarted. A long follow‐up showed the evolution of hypogonadotropic hypogonadism. Molecular studies on NR0B1 revealed a novel and deleterious deletion–insertion–inversion–deletion complex rearrangement sorted in the 5′‐3′ direction, which is described as follows: (1) deletion of the intergenic region (between TASL and NR0B1 genes) and 5′ region, (2) insertion of a sequence containing 37 bp at the junction of the intergenic region of the TASL gene and a part of exon 1 of the NR0B1 gene, (3) inversion of a part of exon 1, (4) deletion of the final portion of exon 1 and exon 2 and beginning of the 3′UTR region, (5) maintenance of part of the intergenic sequence (between genes MAGEB1 and NR0B1, telomeric sense), (6) large posterior deletion, in the same sense. The path to molecular diagnosis was challenging and involved several molecular biology techniques. Evaluating the breakpoints in our patient, we assumed that it was a nonrecurrent rearrangement that had not yet been described. It may involve a repair mechanism known as nonhomologous end‐joining (NHEJ), which joins two ends of DNA in an imprecise manner, generating an “information scar,” represented herein by the 37 bp insertion. In addition, the local Xp21 chromosome architecture with sequences capable of modifying the DNA structure could impact the formation of complex rearrangements.

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Section: Introductionmentioning

confidence: 99%

X‐linked congenital adrenal hypoplasia: Report of long clinical follow‐up and description of a new complex variant in the NR0B1 gene

Esquiaveto‐Aun,

de Mello,

Guaragna

et al. 2024

American J of Med Genetics Pt A

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Growth alterations in rare forms of primary adrenal insufficiency: a neglected issue in paediatric endocrinology

Ferrigno¹,

Cioffi²,

Pellino³

et al. 2022

Endocrine

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Neglected Adrenal Hypoplasia Congenita in Two Siblings with Novel Genetic Mutations in NR0B1 Gene and Notable Clinical Course: A Case Report

Khalili,

Zakeri,

Hadaegh

et al. 2024

EMIDDT

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Background: Adrenal Hypoplasia Congenita (AHC) is a rare subtype of primary adrenal insufficiency (PAI) that can go undiagnosed easily. In this article, we report two brothers with hypogonadotropic hypogonadism and novel mutations in the NR0B1 gene who were misdiagnosed and mismanaged as having congenital adrenal hypoplasia (CAH) for several years. Case Presentation: Herein, we describe two brothers with similar histories; first, they were diagnosed with CAH and treated for that; however, after several years, they showed symptoms of lack of testosterone despite receiving CAH treatment. Low levels of testosterone and LH were detected in both, and a genetic test of CAH was negative for the first brother. Thereafter, DAX- 1 deficiency was suspected, and their genetic tests (the NR0B1 gene) confirmed the diagnosis of DAX-1. Conclusion: The diagnosis of CAH in case of low levels of 17- OHP, testosterone, and LH, as well as central hypogonadotropic hypogonadism, should be studied, and further investigations are mandatory to evaluate other subtypes of PAI, especially AHC.

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Novel mutation in the nuclear receptor subfamily 0, group B, member 1 (NR0B1) gene associated with intrafamilial heterogeneity in three boys with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism from India

Cited by 3 publications

References 0 publications

X‐linked congenital adrenal hypoplasia: Report of long clinical follow‐up and description of a new complex variant in the NR0B1 gene

X‐linked congenital adrenal hypoplasia: Report of long clinical follow‐up and description of a new complex variant in the NR0B1 gene

Growth alterations in rare forms of primary adrenal insufficiency: a neglected issue in paediatric endocrinology

Neglected Adrenal Hypoplasia Congenita in Two Siblings with Novel Genetic Mutations in NR0B1 Gene and Notable Clinical Course: A Case Report

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