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NM_020159.5(SMARCAD1):c.1281+666dup AND Keratoderma with scleroatrophy of the extremities

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 14, 2019
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:
RCV000761205.1

Allele description [Variation Report for NM_020159.5(SMARCAD1):c.1281+666dup]

NM_020159.5(SMARCAD1):c.1281+666dup

Gene:
SMARCAD1:SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD/H box 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
4q22.3
Genomic location:
Preferred name:
NM_020159.5(SMARCAD1):c.1281+666dup
HGVS:
  • NC_000004.12:g.94253673dup
  • NG_031945.1:g.51066dup
  • NM_001128429.3:c.1281+666dup
  • NM_001128430.2:c.1281+666dup
  • NM_001254949.2:c.-10+2dup
  • NM_001375855.1:c.1281+666dup
  • NM_001375856.1:c.1281+666dup
  • NM_001375857.1:c.1278+666dup
  • NM_001375858.1:c.1281+666dup
  • NM_001375859.1:c.-10+2dup
  • NM_020159.5:c.1281+666dupMANE SELECT
  • NC_000004.11:g.95174824dup
Note:
NCBI staff reviewed the trace in Figure 1 of the paper by Günther et al., 2018 (PubMed 29409814) to define the location of this allele.
Links:
OMIM: 612761.0006; dbSNP: rs1560542214
NCBI 1000 Genomes Browser:
rs1560542214
Molecular consequence:
  • NM_001128429.3:c.1281+666dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001128430.2:c.1281+666dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001375855.1:c.1281+666dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001375856.1:c.1281+666dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001375857.1:c.1278+666dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001375858.1:c.1281+666dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_020159.5:c.1281+666dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001254949.2:c.-10+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001375859.1:c.-10+2dup - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Keratoderma with scleroatrophy of the extremities (HRZ)
Synonyms:
Sclerotylosis; Scleroatrophic and keratotic dermatosis of limbs; Huriez syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008416; MedGen: C0406767; OMIM: 181600

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000891121OMIM
no assertion criteria provided
Pathogenic
(Mar 14, 2019) 		germlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

[A gene dysplasia not previously known: frequently degenerative sclero-atrophying and keratodermic genodermatosis of the extremities].

Huriez C, Deminatti M, Agache P, Mennecier M.

Sem Hop. 1968 Feb 14;44(8):481-8. French. No abstract available.

PubMed [citation]
PMID:
4298032

SMARCAD1 Haploinsufficiency Underlies Huriez Syndrome and Associated Skin Cancer Susceptibility.

Günther C, Lee-Kirsch MA, Eckhard J, Matanovic A, Kerscher T, Rüschendorf F, Klein B, Berndt N, Zimmermann N, Flachmeier C, Thuß T, Lucas N, Marenholz I, Esparza-Gordillo J, Hübner N, Traupe H, Delaporte E, Lee YA.

J Invest Dermatol. 2018 Jun;138(6):1428-1431. doi: 10.1016/j.jid.2018.01.015. Epub 2018 Feb 1. No abstract available.

PubMed [citation]
PMID:
29409814

Details of each submission

From OMIM, SCV000891121.1

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

Description

In affected members of a large 5-generation French family (family A) with Huriez syndrome (HRZ; 181600), originally reported by Huriez et al. (1968), Gunther et al. (2018) identified heterozygosity for a 1-bp insertion at the splice donor site of exon 1 (c.378+2insT) in the SMARCAD1 gene. The mutation, which was confirmed by Sanger sequencing, segregated fully with disease in the family and was not found in 400 German controls or the dbSNP (build 146), HapMap (release 28), or 1000 Genomes Project databases. Amplification of cDNA from patient skin showed only wildtype allele, consistent with complete loss of expression of the mutant allele. Western blot analysis of patient keratinocytes and fibroblasts confirmed reduced expression of SMARCAD1. Patient cells showed significantly more DNA double-strand breaks (DSBs) than control cells, and DSBs persisted for 24 hours after ultraviolet irradiation, in contrast to efficient repair of DSBs in control cells. In addition, patient fibroblasts and keratinocytes proliferated significantly slower than control cells, consistent with prolonged arrest of the cell cycle to ensure repair of enhanced basal DNA damage.

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

Last Updated: Aug 5, 2023