title: Dual genetic diagnoses: Atypical hand-foot-genital syndrome and developmental delay due to de novo mutations in HOXA13 and NRXN1.
abstract: We describe a male patient with dual genetic diagnoses of atypical hand-foot-genital syndrome (HFGS) and developmental delay. The proband had features of HFGS that included bilateral vesicoureteric junction obstruction with ectopic ureters, brachydactyly of various fingers and toes, hypoplastic thenar eminences, and absent nails on both 4th toes and right 5th toe. The atypical features of HFGS present were bilateral hallux valgus malformations and bilateral preaxial polydactyly of the hands. Chromosomal microarray analysis identified a de novo 0.5 Mb deletion at 2p16.3, including the first four exons of the NRXN1 gene. Whole exome sequencing and subsequent Sanger sequencing identified a de novo missense mutation (c.1123G>T, p.Val375Phe) in exon 2 of the HOXA13 gene, predicted to be damaging and located in the homeobox domain. The intragenic NRXN1 deletion is thought to explain his developmental delay via a separate genetic mechanism.
authors.affiliation: Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Mathew
authors.initials: M
authors.lastname: Wallis
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Victorian Clinical Genetics Service, MCRI, Royal Children's Hospital, Parkville, Victoria, Australia.|Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Trent
authors.initials: T
authors.lastname: Burgess
authors.affiliation: Department of Paediatric Surgery and Urology, Lady Cilento Children's Hospital, South Brisbane, Queensland, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Borzi
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of General Paediatrics, Lady Cilento Children's Hospital, South Brisbane, Queensland, Australia.
authors.forename: Deanna
authors.initials: D
authors.lastname: True
authors.affiliation: Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Chirag
authors.initials: C
authors.lastname: Patel
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002675:Child, Preschool; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics*; D059472:Exome; D005532:Foot Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014564:Urogenital Abnormalities / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D018398:Homeodomain Proteins; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C099959:homeobox protein HOXA13
keywords: HOXA13; NRXN1; dual diagnosis; hand-foot-genital syndrome; pre-axial polydactyly