A New Split Hand/Foot Malformation with Long Bone Deficiency Familial Case

Carmela Fusco; Pasquelena De Nittis; Ali Abdullah Alfaiz; Maria Teresa Pellico; Bartolomeo Augello; Natascia Malerba; Leopoldo Zelante; Alexandre Reymond; Giuseppe Merla

doi:10.1055/s-0036-1588029

Journal of Pediatric Genetics, Inhaltsverzeichnis

J Pediatr Genet 2017; 06(02): 098-102
DOI: 10.1055/s-0036-1588029

Case Report

Georg Thieme Verlag KG Stuttgart · New York

A New Split Hand/Foot Malformation with Long Bone Deficiency Familial Case

Authors

Carmela Fusco^*

¹ Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
Pasquelena De Nittis^*

¹ Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy

²Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
Ali Abdullah Alfaiz

²Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

³Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne, Switzerland
Maria Teresa Pellico

¹ Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
Bartolomeo Augello

¹ Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
Natascia Malerba

¹ Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
Leopoldo Zelante

¹ Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
Alexandre Reymond

²Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
Giuseppe Merla

¹ Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy

Abstract

Split hand/foot malformation with long bone deficiency (SHFLD) is a congenital limb anomaly where hands and/or feet cleft and syndactyly are associated with long bone defects, usually involving the tibia. Previously published data reported that 17p13.3 chromosomal duplication, including the BHLHA9 gene, has been associated with the distinct entity, termed SHFLD3 (OMIM 612576), inherited as an autosomal dominant trait.

Here, we present a family with three members affected by SHFLD harboring BHLHA9 duplication. We exploited in vitro differentiation system to promote proband's skin fibroblasts toward osteoblastic lineage, and we observed a slight but consistent delay in the mineralization pattern. This result possibly suggests an impairment of the osteogenic process in the affected members.

Keywords

split-hand/foot malformation - SHFLD3 - 17p13.3 microduplication - osteogenic differentiation

Volltext

Referenzen

References
1 Petit F, Jourdain AS, Andrieux J , et al. Split hand/foot malformation with long-bone deficiency and BHLHA9 duplication: report of 13 new families. Clin Genet 2014; 85 (5) 464-469
2 Armour CM, Bulman DE, Jarinova O , et al. 17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD). Eur J Hum Genet 2011; 19 (11) 1144-1151
3 Klopocki E, Lohan S, Doelken SC , et al. Duplications of BHLHA9 are associated with ectrodactyly and tibia hemimelia inherited in non-Mendelian fashion. J Med Genet 2012; 49 (2) 119-125
4 Nagata E, Kano H, Kato F , et al. Japanese founder duplications/triplications involving BHLHA9 are associated with split-hand/foot malformation with or without long bone deficiency and Gollop-Wolfgang complex. Orphanet J Rare Dis 2014; 9: 125 . Doi: 10.1186/s13023-014-0125-5
5 Nagata E, Haga N, Fujisawa Y, Fukami M, Nishimura G, Ogata T. Femoral-tibial-digital malformations in a boy with the Japanese founder triplication of BHLHA9 . Am J Med Genet A 2015; 167A (12) 3226-3228
6 Schatz O, Langer E, Ben-Arie N. Gene dosage of the transcription factor Fingerin (bHLHA9) affects digit development and links syndactyly to ectrodactyly. Hum Mol Genet 2014; 23 (20) 5394-5401
7 Malik S, Percin FE, Bornholdt D , et al. Mutations affecting the BHLHA9 DNA-binding domain cause MSSD, mesoaxial synostotic syndactyly with phalangeal reduction, Malik-Percin type. Am J Hum Genet 2014; 95 (6) 649-659
8 Petit F, Andrieux J, Demeer B , et al. Split-hand/foot malformation with long-bone deficiency and BHLHA9 duplication: two cases and expansion of the phenotype to radial agenesis. Eur J Med Genet 2013; 56 (2) 88-92
9 Bills CE, Eisenberg H, Pallante SL. Complexes of organic acids with calcium phosphate: the von Kossa stain as a clue to the composition of bone mineral. Johns Hopkins Med J 1971; 128 (4) 194-207
10 Lin HH, Hwang SM, Wu SJ , et al. The osteoblastogenesis potential of adipose mesenchymal stem cells in myeloma patients who had received intensive therapy. PLoS ONE 2014; 9 (4) e94395 . Doi: 10.1371/journal.pone.0094395
11 Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000; 132: 365-386
12 Howald C, Merla G, Digilio MC , et al. Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions. J Med Genet 2006; 43 (3) 266-273
13 Ianakiev P, Kilpatrick MW, Toudjarska I, Basel D, Beighton P, Tsipouras P. Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27. Am J Hum Genet 2000; 67 (1) 59-66
14 Rinne T, Hamel B, van Bokhoven H, Brunner HG. Pattern of p63 mutations and their phenotypes—update. Am J Med Genet A 2006; 140 (13) 1396-1406
15 Lo Iacono N, Mantero S, Chiarelli A , et al. Regulation of Dlx5 and Dlx6 gene expression by p63 is involved in EEC and SHFM congenital limb defects. Development 2008; 135 (7) 1377-1388
16 Lorenz K, Sicker M, Schmelzer E , et al. Multilineage differentiation potential of human dermal skin-derived fibroblasts. Exp Dermatol 2008; 17 (11) 925-932

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