Duplications of<i>BHLHA9</i>are associated with ectrodactyly and tibia hemimelia inherited in non-Mendelian fashion

Klopocki, Eva; Lohan, Silke B.; Doelken, Sandra C.; Stricker, Sigmar; Ockeloen, Charlotte W.; Aguiar, Renata Soares Thiele de; Lezirovitz, Karina; Mingroni-Netto, Regina Célia; Jamsheer, Aleksander; Shah, Hitesh; Kurth, Ingo; Habenicht, R.; Warman, Matthew L.; Devriendt, Koenraad; Kordaß, Ulrike; Hempel, Maja; Rajab, Anna; Mäkitie, Outi; Naveed, Mohammed; Radhakrishna, Uppala; Antonarakis, Stylianos E.; Horn, Denise; Mundlos, Stefan

doi:10.1136/jmedgenet-2011-100409

Cited by 85 publications

(133 citation statements)

References 21 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…Type I, the most frequent variety, is due to a mutation on chromosome 7 (rearrangements in 7q21.3-q22.1) in a region that contains two homeobox genes, DLX5 and DLX6. [6][7][8] In our case, the mode of inheritance is autosomal reccesive as only one sibling and no other family members are affected. There have been isolated case reports in the literature of the autosomal recessive inheritance pattern of SHFMs of the non-syndromal type.…”

Section: Discussionmentioning

confidence: 70%

Split-hand/split-foot malformation (SHFM)

et al. 2014

View full text Add to dashboard Cite

A B S T R A C T Access this article online Website:http://nepjol.info/index.php/AJMS Split-hand/split-foot malformation (SHFM), also known as ectrodactyly or lobster claw hand is a congenital limb malformation, characterized by a deep median cleft of the hand and/or foot due to the absence of the central rays of the autopod. It may occur singly or in association with syndromes, former being mostly autosomal dominant but autosomal recessive variety is rare. We are reporting a case of ectrodactyly with autosomal recessive mode of inheritance.

show abstract

Section: Discussionmentioning

confidence: 70%

Split-hand/split-foot malformation (SHFM)

et al. 2014

View full text Add to dashboard Cite

show abstract

“…[28][29][30][31] Copy number gains can result in aberrant expression of genes via a number of mechanisms including increased expression due to dosage effect and disruption of regulatory elements resulting in unusual spatial or temporal expression patterns. The phenotypic variability of LP may reflect differences in the expression of critical genes due to the span or orientation of the duplicated region, even though the microduplications in the two families overlap significantly.…”

Section: Discussionmentioning

confidence: 99%

Leri’s pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22.1 encompassingGDF6andSDC2and provides insight into systemic sclerosis pathogenesis

et al. 2014

View full text Add to dashboard Cite

Our work identifies the genetic cause of LP in these two families, demonstrates the phenotypic range of the condition, implicates dysregulation of extracellular matrix homoeostasis genes in its pathogenesis, and highlights the link between TGF-β/SMAD signalling, growth/differentiation factor 6 and syndecan-2. We propose that LP is an additional member of the growing 'TGF-β-pathies' group of musculoskeletal disorders, which includes Myhre syndrome, acromicric dysplasia, geleophysic dysplasias, Weill-Marchesani syndromes and stiff skin syndrome. Identification of a systemic sclerosis-protective SDC2 variant lays the foundation for exploration of the role of syndecan-2 in systemic sclerosis in the future.

show abstract

“…Hypoplasia of radius and ulna, nail clubbing of the right hand, anonychia of the second finger on the left hand, crowding teeth, and synophrys were observed. Klopocki et al [2012] reported phenotypes with aplasia/hypoplasia of radius and ulna, and microdontia in individuals affected with SHFM due to the duplication of 17p13.3. Shamseldin et al [2012] reported a Yemeni family segregating SHFM1 due to a missense mutation in DLX5 .…”

Section: Mutation Screeningmentioning

confidence: 99%

A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1

et al. 2016

View full text Add to dashboard Cite

Split-hand and foot malformation (SHFM; MIM 183600) is a rare human genetic limb malformation. It is characterized by missing digital rays in the hands and feet. SHFMs vary in severity from mild abnormalities affecting a single limb to acute malformations involving all 4 limbs. It is inherited, as part of both a syndromic and nonsyndromic disorder, in an autosomal recessive, autosomal dominant, and X-linked patterns. So far, 9 loci of hand and foot malformation have been mapped on human chromosomes. The present study describes a family with 2 affected individuals segregating SHFM in an autosomal dominant fashion. Sanger sequencing of the genes involved in SHFM was performed to identify the disease-causing variant. Sequence analysis revealed the first heterozygous missense variant (c.632T>A, p.Val211Glu) in the distal-less homeobox 6 (DLX6) gene, located in chromosome 7q21, causing SHFM in the present family. This study supports the evidence of DLX6 as an SHFM-causing gene.

show abstract

Duplications ofBHLHA9are associated with ectrodactyly and tibia hemimelia inherited in non-Mendelian fashion

Cited by 85 publications

References 21 publications

Split-hand/split-foot malformation (SHFM)

Split-hand/split-foot malformation (SHFM)

Leri’s pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22.1 encompassingGDF6andSDC2and provides insight into systemic sclerosis pathogenesis

A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1

Contact Info

Product

Resources

About