A Tunisian family with a novel mutation in the gene CYP4F22 for lamellar ichthyosis and co-occurrence of hearing loss in a child due to mutation in the SLC26A4 gene.
Journal
International journal of dermatology
ISSN: 1365-4632
Titre abrégé: Int J Dermatol
Pays: England
ID NLM: 0243704
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
28
06
2018
revised:
06
03
2019
accepted:
11
03
2019
pubmed:
26
4
2019
medline:
6
5
2020
entrez:
26
4
2019
Statut:
ppublish
Résumé
Co-occurrence of two genetic diseases is challenging for accurate diagnosis and genetic counseling. The recent availability of whole exome sequencing (WES) has dramatically improved the molecular diagnosis of rare genetic diseases in particular in consanguineous populations. We report here on a consanguineous family from Southern Tunisia including three members affected with congenital ichthyosis. The index case had a hearing loss (HL) and ichthyosis and was primarily suspected as suffering from keratitis-ichthyosis-deafness (KID) syndrome. WES was performed for the index case, and all members of the nuclear family were sequenced (Sanger method). The WES approach allowed the identification of two strong candidate variants in two different genes; a missense mutation c.1334T>G (p.Leu445Trp) in exon 11 of SLC26A4 gene, associated with isolated HL and a novel missense mutation c.728G>T (p.Arg243Leu) in exon 8 of CYP4F22 gene likely responsible for ichthyosis. These two mutations were predicted to be pathogenic by three pathogenicity prediction softwares (Scale-Invariant Feature Transform [SIFT], Polymorphism Phenotyping [PolyPhen], Mutation Taster) to underlie the HL and ichthyosis, respectively. The present study raises awareness about the importance of familial history for accurate diagnosis of syndromic genetic diseases and differential diagnosis with co-occurrence of two distinct clinical entities. In addition, in countries with limited resources, WES sequencing for a single individual provides a cost effective tool for molecular diagnosis confirmation and genetic counseling.
Sections du résumé
BACKGROUND
BACKGROUND
Co-occurrence of two genetic diseases is challenging for accurate diagnosis and genetic counseling. The recent availability of whole exome sequencing (WES) has dramatically improved the molecular diagnosis of rare genetic diseases in particular in consanguineous populations.
METHODS
METHODS
We report here on a consanguineous family from Southern Tunisia including three members affected with congenital ichthyosis. The index case had a hearing loss (HL) and ichthyosis and was primarily suspected as suffering from keratitis-ichthyosis-deafness (KID) syndrome. WES was performed for the index case, and all members of the nuclear family were sequenced (Sanger method).
RESULTS
RESULTS
The WES approach allowed the identification of two strong candidate variants in two different genes; a missense mutation c.1334T>G (p.Leu445Trp) in exon 11 of SLC26A4 gene, associated with isolated HL and a novel missense mutation c.728G>T (p.Arg243Leu) in exon 8 of CYP4F22 gene likely responsible for ichthyosis. These two mutations were predicted to be pathogenic by three pathogenicity prediction softwares (Scale-Invariant Feature Transform [SIFT], Polymorphism Phenotyping [PolyPhen], Mutation Taster) to underlie the HL and ichthyosis, respectively.
CONCLUSIONS
CONCLUSIONS
The present study raises awareness about the importance of familial history for accurate diagnosis of syndromic genetic diseases and differential diagnosis with co-occurrence of two distinct clinical entities. In addition, in countries with limited resources, WES sequencing for a single individual provides a cost effective tool for molecular diagnosis confirmation and genetic counseling.
Substances chimiques
SLC26A4 protein, human
0
Sulfate Transporters
0
Cytochrome P-450 Enzyme System
9035-51-2
CYP4F22 protein, human
EC 1.-
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1439-1443Subventions
Organisme : Tunisian Ministry of Public Health
Organisme : Ministry of Higher Education and Scientific Research
ID : LR11IPT05
Organisme : E.C.
ID : 295097
Informations de copyright
© 2019 The International Society of Dermatology.
Références
Hamamy H, Antonarakis SE, Cavalli-Sforza LL, et al. Consanguineous marriages, pearls and perils: Geneva International Consanguinity Workshop Report. Genet Med 2011; 13: 841-847.
Ben Halim N, Ben Alaya Bouafif N, Romdhane L, et al. Consanguinity, endogamy, and genetic disorders in Tunisia. J Community Genet 2012; 4: 273-284.
Romdhane L, Ben Halim N, Rejeb I, et al. Specific aspects of consanguinity: some examples from the Tunisian population. Hum Hered 2014; 77: 167-174.
Romdhane L, Messaoud O, Bouyacoub Y, et al. Comorbidity in the Tunisian population. Clin Genet 2016; 89: 312-319.
Tadmouri GO, Nair P, Obeid T, et al. Consanguinity and reproductive health among Arabs. Reprod Health 2009; 6: 17.
Oji V, Tadini G, Akiyama M, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009. J Am Acad Dermatol 2010; 63: 607-641.
Herman ML, Farasat S, Steinbach PJ, et al. Transglutaminase-1 gene mutations in autosomal recessive congenital ichthyosis: summary of mutations (including 23 novel) and modeling of TGase-1. Hum Mutat 2009; 30: 537-547.
Pigg M, Gedde-Dahl T Jr, Cox D, et al. Strong founder effect for a transglutaminase 1 gene mutation in lamellar ichthyosis and congenital ichthyosiform erythroderma from Norway. Eur J Hum Genet 1998; 6: 589-596.
Denoyelle F, Marlin S, Weil D, et al. Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling. Lancet 1999; 353: 1298-1303.
Dalamon VK, Buonfiglio P, Larralde M, et al. Connexin 26 (GJB2) mutation in an Argentinean patient with keratitis-ichthyosis-deafness (KID) syndrome: a case report. BMC Med Genet 2016; 17: 37.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
Gudmundsson S, Wilbe M, Ekvall S, et al. Revertant mosaicism repairs skin lesions in a patient with keratitis-ichthyosis-deafness syndrome by second-site mutations in connexin 26. Hum Mol Genet 2017; 26: 1070-1077.
Riahi Z, Hammami H, Ouragini H, et al. Update of the spectrum of GJB2 gene mutations in Tunisian families with autosomal recessive nonsyndromic hearing loss. Gene 2013; 525: 1-4.
Candi E, Melino G, Lahm A, et al. Transglutaminase 1 mutations in lamellar ichthyosis. Loss of activity due to failure of activation by proteolytic processing. J Biol Chem 1998; 273: 13693-13702.
Bahcall OG. Genetic variation: ExAC boosts clinical variant interpretation in rare diseases. Nat Rev Genet 2016; 17: 584.
Ng PC, Henikoff S. Predicting the effects of amino acid substitutions on protein function. Annu Rev Genomics Hum Genet 2006; 7: 61-80.
Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010; 7: 248-249.
Schwarz JM, Cooper DN, Schuelke M, et al. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 2014; 11: 361-362.
Lefevre C, Bouadjar B, Ferrand V, et al. Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Mol Genet 2006; 15: 767-776.
Buckova H, Noskova H, Borska R, et al. Autosomal recessive congenital ichthyoses in the Czech Republic. Br J Dermatol 2016; 174: 405-407.
Lugassy J, Hennies HC, Indelman M, et al. Rapid detection of homozygous mutations in congenital recessive ichthyosis. Arch Dermatol Res 2008; 300: 81-85.
Sugiura K, Takeichi T, Tanahashi K, et al. Lamellar ichthyosis in a collodion baby caused by CYP4F22 mutations in a non-consanguineous family outside the Mediterranean. J Dermatol Sci 2013; 72: 193-195.
Gruber R, Rainer G, Weiss A, et al. Morphological alterations in two siblings with autosomal recessive congenital ichthyosis associated with CYP4F22 mutations. Br J Dermatol 2017; 176: 1068-1073.
Wilcox ER, Everett LA, Li XC, et al. The PDS gene, Pendred syndrome and non-syndromic deafness DFNB4. Adv Otorhinolaryngol 2000; 56: 145-151.
Everett LA, Glaser B, Beck JC, et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 1997; 17: 411-422.
Charfeddine I, Mnejja M, Hammami B, et al. Pendred syndrome in Tunisia. Eur Ann Otorhinolaryngol Head Neck Dis 2010; 127: 7-10.
Wu CC, Yeh TH, Chen PJ, et al. Prevalent SLC26A4 mutations in patients with enlarged vestibular aqueduct and/or Mondini dysplasia: a unique spectrum of mutations in Taiwan, including a frequent founder mutation. Laryngoscope 2005; 115: 1060-1064.
Dai P, Li Q, Huang D, et al. SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause of hearing loss. Genet Med 2008; 10: 586-592.
Masmoudi S, Charfedine I, Hmani M, et al. Pendred syndrome: phenotypic variability in two families carrying the same PDS missense mutation. Am J Med Genet 2000; 90: 38-44.