title: Severe manifestations of hand-foot-genital syndrome associated with a novel HOXA13 mutation.
abstract: We report on a girl with absent nails, short/absent distal phalanges of the second to fifth fingers and toes, short thumbs, absent halluces, and carpo-tarsal coalition who also had genitourinary malformations. Trio-based whole exome sequencing identified a novel de novo mutation (c.1102A>T, p.Ile368Phe) in the HOXA13 gene. Heterozygous HOXA13 mutations have been previously reported in hand-foot-genital syndrome and Guttmacher syndrome, which are variably associated with small nails, short distal and middle phalanges, short thumbs and halluces, but not absent nails. Considering the molecular data, the phenotype in the present patient was defined as the severe end of hand-foot-genital and Guttmacher syndrome spectrum. Our observation expands the clinical spectrum caused by heterozygous HOXA13 mutations and reinforces the difficulty of differential diagnosis on clinical grounds for the disorders with short distal phalanges, short thumbs, and short halluces.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Imagawa
authors.forename: Hülya
authors.initials: H
authors.lastname: Kayserili
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D005260:Female; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011859:Radiography; D014564:Urogenital Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*
chemical_list: D018398:Homeodomain Proteins; C099959:homeobox protein HOXA13
keywords: Guttmacher syndrome; HOXA13; genotype-phenotype correlation; hand-foot-genital syndrome