Split hand/foot malformation with long bone deficiency associated with BHLHA9 gene duplication: a case report and review of literature.
| Title: | Split hand/foot malformation with long bone deficiency associated with BHLHA9 gene duplication: a case report and review of literature. |
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| Authors: | Paththinige CS; Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka. paththinige@yahoo.com.; Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Anuradhapura, 50008, Sri Lanka. paththinige@yahoo.com.; Sirisena ND; Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka.; Escande F; Laboratoire de Biochimie et Oncologie Moléculaire, CHU Lille, F-59000, Lille, France.; Manouvrier S; Clinique de Génétique Guy Fontaine, CHU Lille, F-59000, Lille, France.; Petit F; Clinique de Génétique Guy Fontaine, CHU Lille, F-59000, Lille, France.; Dissanayake VHW; Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo, 00800, Sri Lanka. |
| Source: | BMC medical genetics [BMC Med Genet] 2019 Jun 14; Vol. 20 (1), pp. 108. Date of Electronic Publication: 2019 Jun 14. |
| Publication Type: | Case Reports; Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 100968552 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2350 (Electronic) Linking ISSN: 14712350 NLM ISO Abbreviation: BMC Med Genet Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : BioMed Central, [2000- |
| MeSH Terms: | Gene Duplication*; Basic Helix-Loop-Helix Proteins/*genetics ; Limb Deformities, Congenital/*genetics ; Tibia/*abnormalities; Chromosomes, Human, Pair 17/genetics ; Foot Deformities, Congenital/genetics ; Gene Rearrangement/genetics ; Hand Deformities, Congenital/genetics ; Limb Deformities, Congenital/diagnostic imaging ; Limb Deformities, Congenital/physiopathology ; Tibia/diagnostic imaging ; Tibia/physiopathology ; Chromosome Duplication ; Comparative Genomic Hybridization ; Ectromelia ; Female ; Gene Dosage ; Genetic Association Studies ; Genetic Loci ; Genetic Predisposition to Disease ; Humans ; Infant, Newborn |
| Abstract: | Background: Split hand/foot malformation (SHFM) is a group of congenital skeletal disorders which may occur either as an isolated abnormality or in syndromic forms with extra-limb manifestations. Chromosomal micro-duplication or micro-triplication involving 17p13.3 region has been described as the most common cause of split hand/foot malformation with long bone deficiency (SHFLD) in several different Caucasian and Asian populations. Gene dosage effect of the extra copies of BHLHA9 gene at this locus has been implicated in the pathogenesis of SHFLD.; Case Presentation: The proband was a female child born to non-consanguineous parents. She was referred for genetic evaluation of bilateral asymmetric ectrodactyly involving both hands and right foot along with right tibial hemimelia. The right foot had fixed clubfoot deformity with only 2 toes. The mother had bilateral ectrodactyly involving both hands, but the rest of the upper limbs and both lower limbs were normal. Neither of them had any other congenital malformations or neurodevelopmental abnormalities. Genetic testing for rearrangement of BHLHA9 gene by quantitative polymerase chain reaction confirmed the duplication of the BHLHA9 gene in both the proband and the mother.; Conclusions: We report the first Sri Lankan family with genetic diagnosis of BHLHA9 duplication causing SHFLD. This report along with the previously reported cases corroborate the possible etiopathogenic role of BHLHA9 gene dosage imbalances in SHFM and SHFLD across different populations. |
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| Contributed Indexing: | Keywords: 17p13.3 duplication; BHLHA9; Ectrodactyly; Split hand/foot malformation; Split hand/foot malformation with long bone deficiency |
| Substance Nomenclature: | 0 (Basic Helix-Loop-Helix Proteins); 0 (BHLHA9 protein, human) |
| SCR Disease Name: | Absence of Tibia; Ectrodactyly; Split hand foot deformity; Split-hand-foot malformation with long bone deficiency |
| Entry Date(s): | Date Created: 20190616 Date Completed: 20191202 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC6570964 |
| DOI: | 10.1186/s12881-019-0839-2 |
| PMID: | 31200655 |
| Database: | MEDLINE |
Case Reports; Journal Article; Review