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SHORT COMMUNICATION Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV
Fibroblast Growth Factor Receptor 3 Epidermal Naevus Syndrome with Urothelial Mosaicism for the Activating p . Ser249Cys FGFR3 Mutation
Didier BESSIS 1 , 2 , Julie PLAISANCIÉ 3 , Véronique GASTON 3 and Eric BIETH 3
1
Department of Dermatology , Saint-Eloi Hospital , University Hospital of Montpellier , 80 avenue A . Fliche , FR-34295 Montpellier cedex 5 ,
2
INSERM U1058 , Montpellier , and 3 Department of Medical Genetics , Purpan Hospital , University Hospital of Toulouse , Toulouse , France . E mail : d-bessis @ chu-montpellier . fr Accepted Oct 26 , 2016 ; Epub ahead of print Oct 27 , 2016
Fibroblast growth factor receptor 3 epidermal naevus syndrome ( FGFR3-ENS ), also known as Garcia-Hafner- Happle syndrome , is a rare and distinctive epidermal naevus ( EN ) syndrome , clinically characterized by a systematized keratinocytic EN of soft and velvety type , with inconstant cerebral and skeletal involvement ( 1 ). We report here a new case of FGFR3-ENS with the postzygotic FGFR3 p . Ser249Cys mutation detected in both affected skin and urothelial cells .
CASE REPORT
A 30-month-old girl was referred for assessment of systematized EN . She was born at term and was otherwise healthy , with normal skeletal and neurocognitive development and no remarkable family history . Skin changes were first noted on the neck at 4 months , with spreading to trunk , limbs and face over the first year of life . Physical examination disclosed a systematized and widespread linear brown EN of a soft and velvety type , following Blaschko ’ s lines , associated with confluent thick and papillomatous plaques over the neck , axillary and groin regions ( Fig . 1 ). Histological examination of the EN revealed hyperkeratosis , acanthosis and papillomatosis . Urine sediment failed to reveal haematuria . Ophthalmologic examination , electroencephalogram , total-body skeletal radiographs , and pelvic ultrasonography were normal . Cerebral magnetic resonance imaging ( MRI )
Fig . 1 . Systematized and widespread epidermal naevus distributed along Blaschko ’ s lines . ( a ) Trunk involvement . ( b ) Confluent papillomatosis acanthosis nigricans-like lesions of the axillary area .
Fig . 2 . Detection of the c . 746C > G ( p . Ser249Cys ) FGFR3 mutation in the proband by ( A ) allele-specific PCR and ( B ) Sanger sequencing . ( A ) Genomic DNA was isolated from different types of tissue and subjected to duplex PCR amplification generating 2 amplicons : a first amplicon of 397 bp used as an internal control ( to check the efficiency of the amplification ), and a second smaller amplicon whose reverse primer is located on the c . 746C > G mutation ( expected size 237 bp ). This allele-specific primer allows efficient discrimination of the mutation in cases of mosaicism . The PCR products were then separated by electrophoresis in 2 % agarose gel . Note the single 397 bp amplicon in the healthy control ( gDNA isolated from blood ) in Lane 1 vs . 2 amplicons with similar intensity in the heterozygous control for the c . 746C > G mutation ( trophoblast cells ) in Lane 2 . Lane 3 : presence of the 2 expected amplicons with lower intensity for the smaller amplicon in the proband skin lesion specimen . In this tissue , the c . 746C > G mosaicism was estimated at approximately 30 %. Lane 4 : absence of the mutation in the proband healthy skin specimen . Lane 5 : presence of the 2 expected amplicons in the proband urine sample with mosaicism estimated at 10 %. Lane 6 : absence of the mutation in the proband blood sample . Lane 7 : presence of the 2 expected amplicons in the proband saliva sample : mosaicism was estimated at approximately 5 %. Lane 8 : although very faint , the 2 expected amplicons can be noted in the proband hair sample with mosaicism estimated at approximately 5 %. Lane 9 : negative control . Lane 10 : pBR322 DNA / BsuRI ( HaeIII ) DNA ladder ( Thermo Fisher Scientific , Waltham , MA , USA ). ( B ) Electropherograms generated by Minor Variant Finder ( MVF ) software to detect the c . 746C > G mosaicism in the FGFR3 gene sequencing of , respectively : ( a ) the proband skin lesion specimen , ( b ) the proband urine sample , and ( c ) a negative control . After removing the background noise signal due to sequencing , the c . 746C > G mosaicism was estimated by the MVF software at : ( a ) 34.2 %, ( b ) 8.6 %, and ( c ) 0 % ( no detection of the mutation ) on the respective forward sequences . Note , this mosaicism rate was also calculated on the reverse FGFR3 sequence and the mean of the 2 ratios ( forward and reverse ) was calculated . The position of the c . 746C > G mutation detected by the software is indicated by a vertical blue line . doi : 10.2340 / 00015555-2554 Acta Derm Venereol 2017 ; 97 : 402 – 403
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica .