NM_033163.5(FGF8):c.118T>C (p.Phe40Leu) AND Hypogonadotropic hypogonadism 6 with or without anosmia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 2008
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:: RCV000030887.2

Allele description [Variation Report for NM_033163.5(FGF8):c.118T>C (p.Phe40Leu)]

NM_033163.5(FGF8):c.118T>C (p.Phe40Leu)

Gene:

FGF8:fibroblast growth factor 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q24.32

Genomic location:

Preferred name:

NM_033163.5(FGF8):c.118T>C (p.Phe40Leu)

HGVS:

NC_000010.11:g.101775168A>G
NG_007151.1:g.5903T>C
NM_001206389.2:c.-123-289T>C
NM_006119.6:c.70-256T>C
NM_033163.5:c.118T>CMANE SELECT
NM_033164.4:c.118T>C
NM_033165.5:c.70-289T>C
NP_149353.1:p.Phe40Leu
NP_149354.1:p.Phe40Leu
NC_000010.10:g.103534925A>G
P55075:p.Phe40Leu

Protein change:

F40L; PHE40LEU

Links:

UniProtKB: P55075#VAR_057964; OMIM: 600483.0003; dbSNP: rs137852661

NCBI 1000 Genomes Browser:

rs137852661

Molecular consequence:

NM_001206389.2:c.-123-289T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_006119.6:c.70-256T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_033165.5:c.70-289T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_033163.5:c.118T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033164.4:c.118T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypogonadotropic hypogonadism 6 with or without anosmia (HH6)
Synonyms:: HYPOGONADOTROPIC HYPOGONADISM 6 WITHOUT ANOSMIA; HYPOGONADOTROPIC HYPOGONADISM 6 WITH ANOSMIA
Identifiers:: MONDO: MONDO:0012988; MedGen: C3552574; Orphanet: 478; OMIM: 612702

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029911	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2008)	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

SCV000029911

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2008)

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

Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice.

Falardeau J, Chung WC, Beenken A, Raivio T, Plummer L, Sidis Y, Jacobson-Dickman EE, Eliseenkova AV, Ma J, Dwyer A, Quinton R, Na S, Hall JE, Huot C, Alois N, Pearce SH, Cole LW, Hughes V, Mohammadi M, Tsai P, Pitteloud N.

J Clin Invest. 2008 Aug;118(8):2822-31. doi: 10.1172/JCI34538.

PubMed [citation]

PMID:: 18596921
PMCID:: PMC2441855

Details of each submission

From OMIM, SCV000029911.1

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

Description

In a 19-year-old man who was evaluated at age 15.5 years for delayed puberty and found to have a hypogonadal serum testosterone level with undetectable serum gonadotropins (HH6; 612702), Falardeau et al. (2008) identified homozygosity for a 118T-C transition in exon 1C of the FGF8 gene, resulting in a phe40-to-leu (F40L) substitution at a highly conserved residue present in the FGF8e and FGF8f isoforms of the protein. Structural and in vitro biochemical analysis of the mutation demonstrated a loss of function; the mutation was not found in 180 ethnically matched controls. The patient, who had a normal brain MRI, was also found to be compound heterozygous for mutations in the FGFR1 gene, Q784H (136350.0023) and D768Y (136350.0024).

#	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: Oct 8, 2024

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