NM_001159702.2(FHL1):c.625T>C (p.Cys209Arg) AND Emery-Dreifuss muscular dystrophy 6

Clinical significance:Pathogenic (Last evaluated: Jan 1, 2010)

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:
RCV000012313.13

Allele description [Variation Report for NM_001159702.2(FHL1):c.625T>C (p.Cys209Arg)]

NM_001159702.2(FHL1):c.625T>C (p.Cys209Arg)

Gene:
FHL1:four and a half LIM domains 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq26.3
Genomic location:
Preferred name:
NM_001159702.2(FHL1):c.625T>C (p.Cys209Arg)
HGVS:
  • NC_000023.11:g.136208578T>C
  • NG_015895.1:g.66179T>C
  • NM_001159699.1:c.673T>C
  • NM_001159702.2:c.625T>C
  • NM_001159703.1:c.501+617T>C
  • NP_001153171.1:p.Cys225Arg
  • NP_001153174.1:p.Cys209Arg
  • NC_000023.10:g.135290737T>C
  • NR_027621.1:n.1036T>C
  • Q13642:p.Cys209Arg
Protein change:
C209R; CYS209ARG
Links:
UniProtKB: Q13642#VAR_075357; OMIM: 300163.0011; dbSNP: rs122459149
NCBI 1000 Genomes Browser:
rs122459149
Molecular consequence:
  • NM_001159703.1:c.501+617T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001159702.2:c.625T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027621.1:n.1036T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Emery-Dreifuss muscular dystrophy 6 (EDMD6)
Identifiers:
MedGen: C2749106

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000032547OMIMno assertion criteria providedPathogenic
(Jan 1, 2010)
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

Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy.

Gueneau L, Bertrand AT, Jais JP, Salih MA, Stojkovic T, Wehnert M, Hoeltzenbein M, Spuler S, Saitoh S, Verschueren A, Tranchant C, Beuvin M, Lacene E, Romero NB, Heath S, Zelenika D, Voit T, Eymard B, Ben Yaou R, Bonne G.

Am J Hum Genet. 2009 Sep;85(3):338-53. doi: 10.1016/j.ajhg.2009.07.015. Epub 2009 Aug 27.

PubMed [citation]
PMID:
19716112
PMCID:
PMC2771595

Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation.

Knoblauch H, Geier C, Adams S, Budde B, Rudolph A, Zacharias U, Schulz-Menger J, Spuler A, Yaou RB, N├╝rnberg P, Voit T, Bonne G, Spuler S.

Ann Neurol. 2010 Jan;67(1):136-40. doi: 10.1002/ana.21839.

PubMed [citation]
PMID:
20186852

Details of each submission

From OMIM, SCV000032547.2

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

Description

In affected members of a large family with Emery-Dreifuss muscular dystrophy-6 (EDMD6; see 300696), Gueneau et al. (2009) identified a 625C-T transition in exon 6 of the FHL1 gene, resulting in a cys209-to-arg (C209R) substitution affecting a highly conserved cys residue of the LIM3 domain of the FHL1A and FHL1B isoforms. The proband presented at age 11 years with stiff neck. He later developed scapular and pelvic muscle weakness and atrophy, multiple joint contractures, scoliosis, and increased serum creatine kinase. At age 39, he had cardiac arrhythmias and cardiac hypertrophy; He died suddenly at age 51. Most affected family members had both cardiac disease and myopathy, although some had only isolated cardiac disease or myopathy. There were several affected females who were heterozygous for the mutation. Skeletal muscle biopsy of the proband showed a dystrophic pattern and moderately decreased FHL1 protein expression.

Knoblauch et al. (2010) identified the C209R mutation in 9 affected male members of a large 4-generation German family with EDMD6. Age at onset was in the first or second decade, and all had contractures and rigid spine. Five had hypertrophic cardiomyopathy, 2 had left ventricular hypertrophy with fibrosis and hypertension, 1 had apical myocardial thinning, and 1 had normal cardiac findings. Only 1 had conduction abnormalities, and only 1 had clear muscle weakness; most appeared muscular but not athletic. Two female carriers of the mutation had rigid spine symptoms, and 1 had left ventricular hypertrophy with hypertension. None of the patients was or became wheelchair-bound. Skeletal muscle biopsy from 3 patients showed cytoplasmic bodies, but not reducing bodies, and dystrophic features. Western blot analysis showed decreased expression of FHL1.

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

Last Updated: Apr 8, 2019

Support Center