NM_001104631.2(PDE4D):c.677T>G (p.Phe226Cys) AND Acrodysostosis 2 with or without hormone resistance

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 1, 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:: RCV000087310.6

Allele description [Variation Report for NM_001104631.2(PDE4D):c.677T>G (p.Phe226Cys)]

NM_001104631.2(PDE4D):c.677T>G (p.Phe226Cys)

Gene:

PDE4D:phosphodiesterase 4D [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q11.2

Genomic location:

Preferred name:

NM_001104631.2(PDE4D):c.677T>G (p.Phe226Cys)

HGVS:

NC_000005.10:g.59193507A>C
NG_027957.2:g.1335823T>G
NM_001104631.2:c.677T>GMANE SELECT
NM_001165899.2:c.494T>G
NM_001197218.2:c.485T>G
NM_001197219.2:c.311T>G
NM_001197220.2:c.287T>G
NM_001349241.2:c.464T>G
NM_001349242.2:c.347T>G
NM_001349243.2:c.-18T>G
NM_001364599.1:c.494T>G
NM_001364600.2:c.494T>G
NM_001364602.2:c.485T>G
NM_001364603.1:c.-274T>G
NM_001364604.1:c.-18T>G
NM_006203.5:c.269T>G
NP_001098101.1:p.Phe226Cys
NP_001159371.1:p.Phe165Cys
NP_001184147.1:p.Phe162Cys
NP_001184148.1:p.Phe104Cys
NP_001184149.1:p.Phe96Cys
NP_001336170.1:p.Phe155Cys
NP_001336171.1:p.Phe116Cys
NP_001351528.1:p.Phe165Cys
NP_001351529.1:p.Phe165Cys
NP_001351531.1:p.Phe162Cys
NP_006194.2:p.Phe90Cys
NC_000005.9:g.58489333A>C

Protein change:

F104C; PHE226CYS

Links:

OMIM: 600129.0009; dbSNP: rs397514465

NCBI 1000 Genomes Browser:

rs397514465

Molecular consequence:

NM_001349243.2:c.-18T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001364603.1:c.-274T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001364604.1:c.-18T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001104631.2:c.677T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001165899.2:c.494T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001197218.2:c.485T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001197219.2:c.311T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001197220.2:c.287T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001349241.2:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001349242.2:c.347T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364599.1:c.494T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364600.2:c.494T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364602.2:c.485T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006203.5:c.269T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Acrodysostosis 2 with or without hormone resistance
Synonyms:: ACRODYSOSTOSIS 2 WITH HORMONE RESISTANCE; ACRODYSOSTOSIS 2 WITHOUT HORMONE RESISTANCE
Identifiers:: MONDO: MONDO:0013822; MedGen: C3553250; Orphanet: 280651; OMIM: 614613

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000120190	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 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

SCV000120190

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 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

Different mutations in PDE4D associated with developmental disorders with mirror phenotypes.

Lindstrand A, Grigelioniene G, Nilsson D, Pettersson M, Hofmeister W, Anderlid BM, Kant SG, Ruivenkamp CA, Gustavsson P, Valta H, Geiberger S, Topa A, Lagerstedt-Robinson K, Taylan F, Wincent J, Laurell T, Pekkinen M, Nordenskjöld M, Mäkitie O, Nordgren A.

J Med Genet. 2014 Jan;51(1):45-54. doi: 10.1136/jmedgenet-2013-101937. Epub 2013 Nov 7.

PubMed [citation]

PMID:: 24203977

Details of each submission

From OMIM, SCV000120190.4

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

Description

In a 14.7-year-old boy with acrodysostosis-2 with hormone resistance (ACRDYS2; 614613), Lindstrand et al. (2014) identified a de novo heterozygous c.677T-G transversion in exon 3 of the PDE4D gene, resulting in a phe226-to-cys (F226C) substitution in the UCR1 domain. The patient had short stature, maxillary hypoplasia, short nose with bulbous tip, red hair, blue eyes, small hands and feet, and brachydactyly. He also had speech delay and intellectual disability. Laboratory studies showed mild parathyroid hormone resistance and type 1 diabetes mellitus. Overexpression of mutant mRNA into zebrafish embryos caused developmental defects, including short curved body with fragile tail, microcephaly, heart edema, cyclopia, and a protruding jaw in 20% of embryos. Lindstrand et al. (2014) postulated that the mutation caused a loss of function in the regulatory region, resulting in increased PDE activity and decreased cellular cAMP with a dominant-negative effect.

#	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: Mar 10, 2024

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