NM_000475.5(NR0B1):c.1231_1234del (p.Leu411fs) AND Congenital adrenal hypoplasia, X-linked

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 18, 2021
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000011714.3

Allele description [Variation Report for NM_000475.5(NR0B1):c.1231_1234del (p.Leu411fs)]

NM_000475.5(NR0B1):c.1231_1234del (p.Leu411fs)

Gene:

NR0B1:nuclear receptor subfamily 0 group B member 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xp21.2

Genomic location:

Preferred name:

NM_000475.5(NR0B1):c.1231_1234del (p.Leu411fs)

HGVS:

NC_000023.11:g.30304759_30304762del
NG_009814.1:g.9618_9621del
NM_000475.5:c.1231_1234delMANE SELECT
NP_000466.2:p.Leu411fs
LRG_858t1:c.1231_1234del
LRG_858:g.9618_9621del
LRG_858p1:p.Leu411fs
NC_000023.10:g.30322875_30322878del
NC_000023.10:g.30322876_30322879del
NM_000475.4:c.1231_1234delCTCA
NM_000475.5:c.1231_1234delCTCAMANE SELECT

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

L411fs

Links:

OMIM: 300473.0019; dbSNP: rs1569268070

NCBI 1000 Genomes Browser:

rs1569268070

Molecular consequence:

NM_000475.5:c.1231_1234del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Congenital adrenal hypoplasia, X-linked (AHC)
Synonyms:: ADRENAL HYPOPLASIA, CONGENITAL, WITH HYPOGONADOTROPIC HYPOGONADISM; X-linked AHC; Adrenal hypoplasia, congenital; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010264; MedGen: C0342482; OMIM: 300200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000031946	OMIM	no assertion criteria provided	Pathogenic (May 1, 1999)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001652695	Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University	no assertion criteria provided	Pathogenic (May 18, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000031946

OMIM

no assertion criteria provided

Pathogenic
(May 1, 1999)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV001652695

Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University

no assertion criteria provided

Pathogenic
(May 18, 2021)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
Asian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A microdeletion within DAX-1 in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism.

Wang J, Killinger DW, Hegele RA.

J Investig Med. 1999 May;47(5):232-5.

PubMed [citation]

PMID:: 10361383

Details of each submission

From OMIM, SCV000031946.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 42-year-old patient who had congenital adrenal hypoplasia with hypogonadotropic hypogonadism (300200), Wang et al. (1999) identified a 4-bp deletion (1464delACTC) in the second exon of the NR0B1 sequence, which caused a frameshift and predicted a premature stop codon at amino acid 416. The diagnosis of AHC and HHG had been made at 2 weeks of age when he presented to the Hospital for Sick Children in Toronto with vomiting, loose stools, and failure to thrive. He was treated with intramuscular deoxycortisone acetate (DOCA) and discharged with 2 subcutaneous DOCA pellets. Prednisone was started with added salt at the age of 23 months. He had been maintained on glucocorticoids since that time. At age 15 he developed a slipped left femoral epiphysis, which was treated surgically. His bone age at that time was 11 years. He had no secondary sexual development when studied at the age of 17 years and was started on testosterone. No other family members were affected.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, SCV001652695.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Asian	1	not provided	not provided	clinical testing	not provided

Description

ADRENAL HYPOPLASIA, CONGENITAL with tiny adrenal glands and mineralocorticoid deficiency

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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