NM_001079668.3(NKX2-1):c.464-2A>G AND Choreoathetosis, hypothyroidism, and neonatal respiratory distress

Clinical significance:Pathogenic (Last evaluated: Jun 15, 2009)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000009545.4

Allele description [Variation Report for NM_001079668.3(NKX2-1):c.464-2A>G]

NM_001079668.3(NKX2-1):c.464-2A>G

Genes:
NKX2-1:NK2 homeobox 1 [Gene - OMIM - HGNC]
SFTA3:surfactant associated 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q13.3
Genomic location:
Preferred name:
NM_001079668.3(NKX2-1):c.464-2A>G
HGVS:
  • NC_000014.9:g.36518022T>C
  • NG_013365.1:g.7204A>G
  • NM_001079668.3:c.464-2A>GMANE SELECT
  • NM_003317.4:c.374-2A>G
  • NC_000014.8:g.36987227T>C
  • NM_001079668.2:c.464-2A>G
Nucleotide change:
IVS2AS, A-G, -2
Links:
OMIM: 600635.0011; dbSNP: rs587776708
NCBI 1000 Genomes Browser:
rs587776708
Molecular consequence:
  • NM_001079668.3:c.464-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_003317.4:c.374-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Choreoathetosis, hypothyroidism, and neonatal respiratory distress (CAHTP)
Synonyms:
BRAIN-LUNG-THYROID SYNDROME; CHOREOATHETOSIS AND CONGENITAL HYPOTHYROIDISM WITH PULMONARY DYSFUNCTION
Identifiers:
MONDO: MONDO:0012593; MedGen: C1970269; Orphanet: 209905; OMIM: 610978

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000029763OMIMno assertion criteria providedPathogenic
(Jun 15, 2009)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1.

Doyle DA, Gonzalez I, Thomas B, Scavina M.

J Pediatr. 2004 Aug;145(2):190-3.

PubMed [citation]
PMID:
15289765

Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case.

Carré A, Szinnai G, Castanet M, Sura-Trueba S, Tron E, Broutin-L'Hermite I, Barat P, Goizet C, Lacombe D, Moutard ML, Raybaud C, Raynaud-Ravni C, Romana S, Ythier H, Léger J, Polak M.

Hum Mol Genet. 2009 Jun 15;18(12):2266-76. doi: 10.1093/hmg/ddp162. Epub 2009 Mar 31.

PubMed [citation]
PMID:
19336474

Details of each submission

From OMIM, SCV000029763.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In 4 affected members of a 3-generation family with autosomal dominant congenital hypothyroidism, neonatal respiratory distress, and choreoathetosis (CAHTP; 610978), Doyle et al. (2004) identified a heterozygous A-to-G transition (376-2A-G) in intron 2 of the TITF1 gene. The mutation was predicted to prevent splicing of exons 2 and 3, resulting in a truncated protein and haploinsufficiency of the gene product.

Carre et al. (2009) identified heterozygosity for the 376-2A-G mutation in monozygotic twins. The mutation occurred de novo. One twin showed neonatal respiratory distress, congenital hypothyroidism, developed chronic pulmonary infections, and was diagnosed with choreoathetosis at age 5 years. The other twin showed neonatal respiratory distress and congenital hypothyroidism but had no respiratory problems after the neonatal period and had no neurologic symptoms through age 16 years.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 17, 2020

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