Tags

Type your tag names separated by a space and hit enter

Complex postaxial polydactyly types A and B with camptodactyly, hypoplastic third toe, zygodactyly and other digit anomalies caused by a novel GLI3 mutation.
Eur J Med Genet. 2017 May; 60(5):268-274.EJ

Abstract

Polydactyly is a phenotypically and genetically highly heterogeneous limb malformation with preaxial and postaxial subtypes and subtypes A and B. Most polydactyly entities are associated with GLI3 mutation. We report on 10 affected individuals from a large Pakistani kindred initially evaluated as a possible new condition. The phenotype is postaxial polydactyly types A and B associated with zygodactyly, postaxial webbing of toes and additional features not previously reported for isolated polydactyly such as camptodactyly, hypoplasia of third toe, and wide space between hallux and second toe. Hypothesizing that the disorder could have resulted from a mutation in a novel gene responsible for polydactyly, we launched a genetic investigation. By linkage mapping and exome sequencing in the most severe case, we identified novel heterozygous frameshift mutation NM_000168.5 (GLI3): c.3635delG (p.(Gly1212Alafs*18)) but did not detect any other possibly deleterious mutation that could explain the unusual features of camptodactyly, hypoplasia of third toe and wide space between first and second toes. Our findings further expand the phenotypic variability of GLI3 polydactyly. We also present a review of GLI3-associated isolated limb anomalies, which indicates that GLI3 mutation leads primarily to two well-established polydactyly types: postaxial types A and B and crossed polydactyly type I. In addition, a variety of other minor digit anomalies generally accompany polydactyly, and there is no straightforward genotype-polydactyly phenotype correlation.

Authors+Show Affiliations

Human Genetics Program, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey.Human Genetics Program, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey. Electronic address: tolun@boun.edu.tr.Human Genetics Program, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: malik@qau.edu.pk.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

28315472

Citation

Mumtaz, Sara, et al. "Complex Postaxial Polydactyly Types a and B With Camptodactyly, Hypoplastic Third Toe, Zygodactyly and Other Digit Anomalies Caused By a Novel GLI3 Mutation." European Journal of Medical Genetics, vol. 60, no. 5, 2017, pp. 268-274.
Mumtaz S, Yıldız E, Lal K, et al. Complex postaxial polydactyly types A and B with camptodactyly, hypoplastic third toe, zygodactyly and other digit anomalies caused by a novel GLI3 mutation. Eur J Med Genet. 2017;60(5):268-274.
Mumtaz, S., Yıldız, E., Lal, K., Tolun, A., & Malik, S. (2017). Complex postaxial polydactyly types A and B with camptodactyly, hypoplastic third toe, zygodactyly and other digit anomalies caused by a novel GLI3 mutation. European Journal of Medical Genetics, 60(5), 268-274. https://doi.org/10.1016/j.ejmg.2017.03.004
Mumtaz S, et al. Complex Postaxial Polydactyly Types a and B With Camptodactyly, Hypoplastic Third Toe, Zygodactyly and Other Digit Anomalies Caused By a Novel GLI3 Mutation. Eur J Med Genet. 2017;60(5):268-274. PubMed PMID: 28315472.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Complex postaxial polydactyly types A and B with camptodactyly, hypoplastic third toe, zygodactyly and other digit anomalies caused by a novel GLI3 mutation. AU - Mumtaz,Sara, AU - Yıldız,Esra, AU - Lal,Karmoon, AU - Tolun,Aslıhan, AU - Malik,Sajid, Y1 - 2017/03/14/ PY - 2016/10/19/received PY - 2017/03/07/revised PY - 2017/03/11/accepted PY - 2017/3/21/pubmed PY - 2017/5/11/medline PY - 2017/3/19/entrez KW - Camptodactyly KW - GLI3 KW - Genotype-phenotype correlation KW - Pakistani family KW - Postaxial polydactyly KW - Supernumerary digits KW - Syndactyly SP - 268 EP - 274 JF - European journal of medical genetics JO - Eur J Med Genet VL - 60 IS - 5 N2 - Polydactyly is a phenotypically and genetically highly heterogeneous limb malformation with preaxial and postaxial subtypes and subtypes A and B. Most polydactyly entities are associated with GLI3 mutation. We report on 10 affected individuals from a large Pakistani kindred initially evaluated as a possible new condition. The phenotype is postaxial polydactyly types A and B associated with zygodactyly, postaxial webbing of toes and additional features not previously reported for isolated polydactyly such as camptodactyly, hypoplasia of third toe, and wide space between hallux and second toe. Hypothesizing that the disorder could have resulted from a mutation in a novel gene responsible for polydactyly, we launched a genetic investigation. By linkage mapping and exome sequencing in the most severe case, we identified novel heterozygous frameshift mutation NM_000168.5 (GLI3): c.3635delG (p.(Gly1212Alafs*18)) but did not detect any other possibly deleterious mutation that could explain the unusual features of camptodactyly, hypoplasia of third toe and wide space between first and second toes. Our findings further expand the phenotypic variability of GLI3 polydactyly. We also present a review of GLI3-associated isolated limb anomalies, which indicates that GLI3 mutation leads primarily to two well-established polydactyly types: postaxial types A and B and crossed polydactyly type I. In addition, a variety of other minor digit anomalies generally accompany polydactyly, and there is no straightforward genotype-polydactyly phenotype correlation. SN - 1878-0849 UR - https://www.unboundmedicine.com/medline/citation/28315472/Complex_postaxial_polydactyly_types_A_and_B_with_camptodactyly_hypoplastic_third_toe_zygodactyly_and_other_digit_anomalies_caused_by_a_novel_GLI3_mutation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1769-7212(16)30401-3 DB - PRIME DP - Unbound Medicine ER -