NM_000611.6(CD59):c.146del (p.Asp49fs) AND Primary CD59 deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 2, 2014
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:: RCV000087130.3

Allele description [Variation Report for NM_000611.6(CD59):c.146del (p.Asp49fs)]

NM_000611.6(CD59):c.146del (p.Asp49fs)

Gene:

CD59:CD59 molecule (CD59 blood group) [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11p13

Genomic location:

Preferred name:

NM_000611.6(CD59):c.146del (p.Asp49fs)

HGVS:

NC_000011.10:g.33717393del
NG_008057.1:g.24086del
NM_000611.6:c.146delMANE SELECT
NM_001127223.1:c.146del
NM_001127225.2:c.146del
NM_001127226.2:c.146del
NM_001127227.2:c.146del
NM_203329.3:c.146del
NM_203330.2:c.146del
NM_203331.3:c.146del
NP_000602.1:p.Asp49fs
NP_001120695.1:p.Asp49fs
NP_001120697.1:p.Asp49fs
NP_001120698.1:p.Asp49fs
NP_001120699.1:p.Asp49fs
NP_976074.1:p.Asp49fs
NP_976075.1:p.Asp49fs
NP_976076.1:p.Asp49fs
LRG_41t1:c.146del
LRG_41:g.24086del
LRG_41p1:p.Asp49fs
NC_000011.9:g.33738939del

Protein change:

D49fs

Links:

OMIM: 107271.0003; dbSNP: rs587777149

NCBI 1000 Genomes Browser:

rs587777149

Molecular consequence:

NM_000611.6:c.146del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127223.1:c.146del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127225.2:c.146del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127226.2:c.146del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127227.2:c.146del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_203329.3:c.146del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_203330.2:c.146del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_203331.3:c.146del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Primary CD59 deficiency
Synonyms:: Cd59 deficiency; HEMOLYTIC ANEMIA, CD59-MEDIATED; CD59-mediated hemolytic anemia with or without immune-mediated polyneuropathy
Identifiers:: MONDO: MONDO:0012858; MedGen: C2676767; Orphanet: 169464; OMIM: 612300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000119991	OMIM	no assertion criteria provided	Pathogenic (Jan 2, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000119991

OMIM

no assertion criteria provided

Pathogenic
(Jan 2, 2014)

germline

literature only

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

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

Citations

PubMed

Targeted therapy with eculizumab for inherited CD59 deficiency.

Höchsmann B, Dohna-Schwake C, Kyrieleis HA, Pannicke U, Schrezenmeier H.

N Engl J Med. 2014 Jan 2;370(1):90-2. doi: 10.1056/NEJMc1308104. No abstract available.

PubMed [citation]

PMID:: 24382084

Details of each submission

From OMIM, SCV000119991.1

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

Description

In a girl with CD59 deficiency (HACD59; 612300), progressive neurologic dysfunction, and hemolytic anemia, Hochsmann et al. (2014) identified a homozygous 1-bp deletion (c.146delA) in exon 5 of the CD59 gene, resulting in a frameshift and premature termination (Asp49ValfsTer31). Her unaffected parents were heterozygous for the mutation. The patient first presented at age 7 months with generalized hypotonia, bulbar symptoms, and areflexia. During later febrile episodes, she developed hemolytic anemia with progressive neurologic deterioration, including T2-weighted hyperintense lesions on brain MRI, seizures, and visual impairment. Flow cytometric analysis of patient peripheral blood cells showed isolated CD59 deficiency. Treatment with eculizumab, an inhibitor of the complement membrane-attack complex, resulted in neurologic improvement about 6 months later. At age 5.5 years, the patient could eat and swallow normally, could walk short distances with support, and had improved cognitive and speech production.

#	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

Last Updated: Apr 23, 2022

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