Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Split hand/split foot malformation, deafness, and mental retardation with a complex cytogenetic rearrangement involving 7q21.3.

ABSTRACT: Split hand/split foot malformation (SHSF) has been described in several patients associated with cytogenetically visible rearrangements involving chromosome 7q. Characterisation of these patients has led to localisation of an autosomal dominant form of SHSF to 7q21-22; the locus has been designated SHFM1. We describe a patient with a complex, apparently balanced cytogenetic rearrangement, including a translocation breakpoint at 7q21.3 near the DSS1 gene. In addition to ectrodactyly of all four limbs, the patient has congenital deafness, submucous cleft palate, microcephaly, and mental retardation. This patient represents an additional case of syndromic ectrodactyly related to the SHFM1 gene region, which may be responsible for both syndromic and non-syndromic ectrodactyly.

SUBMITTER: Ignatius J

PROVIDER: S-EPMC1050639 | biostudies-other | 1996 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Split hand/split foot malformation, deafness, and mental retardation with a complex cytogenetic rearrangement involving 7q21.3.

Ignatius J J Knuutila S S Scherer S W SW Trask B B Kere J J

Journal of medical genetics 19960601 6

Split hand/split foot malformation (SHSF) has been described in several patients associated with cytogenetically visible rearrangements involving chromosome 7q. Characterisation of these patients has led to localisation of an autosomal dominant form of SHSF to 7q21-22; the locus has been designated SHFM1. We describe a patient with a complex, apparently balanced cytogenetic rearrangement, including a translocation breakpoint at 7q21.3 near the DSS1 gene. In addition to ectrodactyly of all four l ...[more]

PMID: 8782053

Similar Datasets

Nonsyndromic Split-Hand/Foot Malformation: Recent Classification.

Project description:Split-hand/foot malformation (SHFM) is a genetic limb anomaly disturbing the central rays of the autopod. SHFM is a genetically heterogeneous disorder with variable expressivity inherited as syndromic and nonsyndromic forms. We provide an update of the clinical and molecular aspects of nonsyndromic SHFM. This rare condition is highly complex due to the clinical variability and irregular genetic inheritance observed in the affected individuals. Nonsyndromic SHFM types have been reviewed in terms of major molecular genetic alterations reported to date. This updated overview will assist researchers, scientists, and clinicians in making an appropriate molecular diagnosis, providing an accurate recurrence risk assessment, and developing a management plan.

| S-EPMC6997797 | biostudies-literature

Genetic analysis of a congenital split?hand/split?foot malformation 4 pedigree.

Project description:In the present study whole-exome sequencing using the Complete Genomics platform was employed to scan a proband from a split?hand/split?foot malformation (SHFM) 4 family. The missense mutation c.728G>A (p.Arg243Gln) in the TP63 gene was revealed to be associated with SHFM. Sanger sequencing confirmed the sequences of the proband and his father. The father was diagnosed with SHFM and harbored a CGG?to?CAG mutation in exon 5, which produced a R243Q substitution in the zinc binding site and dimerization site of TP63. The R243Q mutation was predicted to be pathogenic by PolyPhen?2. The proband, who was diagnosed with four digit SHFM, exhibited a more severe phenotype. X?ray analysis returned the following results: Absence of third phalange bilaterally and third metacarpus of the left hand; absence of the second toes bilaterally and partial third toes; and partial fusion of the second, third and metatarsal bones of the right side with deformity of the second metatarsal of the right side. Osteochondroma was present in the fourth proximal radial metacarpal of the left hand and the basal and proximal parts of the second metatarsal of the right side. The proband's father had five digits in both feet. These results indicate that the R243Q mutation produces a novel phenotype named SHFM4. The present study revealed that the R243Q mutation in the TP63 gene produced a novel phenotype named SHFM4, thereby demonstrating the mutational overlap between ectrodactyly?ectodermal dysplasia?cleft syndrome and SHFM4.

| S-EPMC5983954 | biostudies-literature

Reconstruction of a Monodactylous Hand with Microsurgical Free Foot-to-Hand Transfer in Split-Hand/Split-Foot Malformation with Tibial Aplasia.

Project description:Split-hand/split-foot malformation with long bone deficiency (SHLFD syndrome) is a rare congenital disorder, which may be sporadic or autosomal dominant with incomplete penetrance. When complete tibial aplasia is seen, the mainstay of treatment is amputation and lower limb prosthesis. This rare constellation of congenital differences presents an opportunity for microsurgical free tissue transfer using the principle of "spare parts" to improve the functionality of the hand. We present a rare case of split-hand/split-foot malformation with a monodactylous right hand and complete tibial aplasia, treated with microsurgical free foot-to-hand transfer at the time of lower limb amputation, reconstructing key pinch. At the latest 8 months follow-up, the patient had no pain, active key pinch, and ambulated independently with prostheses. He was able to use his right hand independently for a number of daily activities, such as stacking blocks, drinking from a cup, and playing with toys.

| S-EPMC7159962 | biostudies-literature

Evidence for locus heterogeneity in human autosomal dominant split hand/split foot malformation.

Project description:Split hand/split foot (SHSF; also known as ectrodactyly) is a human developmental disorder characterized by missing central digits and other distal limb malformations. An association between SHSF and cytogenetically visible rearrangements of chromosome 7 at bands q21-q22 provides compelling evidence for the location of a causative gene at this location, and the locus has been designated SHFD1. In the present study, marker loci were localized to the SHFD1 critical region through the analysis of somatic cell hybrids derived from individuals with SHSF and cytogenetic abnormalities involving the 7q21-q22 region. Combined genetic and physical data suggest that the order of markers in the SHFD1 critical region is cen-D7S492-D7S527-(D7S479-D7S491)-SHFD1-++ +D7S554-D7S518-qter. Dinucleotide repeat polymorphisms at three of these loci were used to test for linkage of SHSF to this region in a large pedigree that demonstrates autosomal dominant SHSF. Evidence against linkage of the SHSF gene to 7q21-q22 was obtained in this pedigree. Therefore, combined molecular and genetic data provide evidence for locus heterogeneity in autosomal dominant SHSF. We propose the name SHSF2 for this second locus.

| S-EPMC1918225 | biostudies-other

Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27.

Project description:Split-hand/split-foot malformation (SHFM), a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals, is phenotypically analogous to the naturally occurring murine Dactylaplasia mutant (Dac). Results of recent studies have shown that, in heterozygous Dac embryos, the central segment of the apical ectodermal ridge (AER) degenerates, leaving the anterior and posterior segments intact; this finding suggests that localized failure of ridge maintenance activity is the fundamental developmental defect in Dac and, by inference, in SHFM. Results of gene-targeting studies have demonstrated that p63, a homologue of the cell-cycle regulator TP53, plays a critically important role in regulation of the formation and differentiation of the AER. Two missense mutations, 724A-->G, which predicts amino acid substitution K194E, and 982T-->C, which predicts amino acid substitution R280C, were identified in exons 5 and 7, respectively, of the p63 gene in two families with SHFM. Two additional mutations (279R-->H and 304R-->Q) were identified in families with EEC (ectrodactyly, ectodermal dysplasia, and facial cleft) syndrome. All four mutations are found in exons that fall within the DNA-binding domain of p63. The two amino acids mutated in the families with SHFM appear to be primarily involved in maintenance of the overall structure of the domain, in contrast to the p63 mutations responsible for EEC syndrome, which reside in amino acid residues that directly interact with the DNA.

| S-EPMC1287102 | biostudies-literature

Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation.

Project description:Split-hand/split-foot malformation (SHFM), also known as ectrodactyly is a rare genetic disorder. It is a clinically and genetically heterogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. To date, seven genes underlying SHFM have been identified. This study described four consanguineous families (A-D) segregating SHFM in an autosomal recessive manner. Linkage in the families was established to chromosome 12p11.1-q13.13 harboring WNT10B gene. Sequence analysis identified a novel homozygous nonsense variant (p.Gln154*) in exon 4 of the WNT10B gene in two families (A and B). In the other two families (C and D), a previously reported variant (c.300_306dupAGGGCGG; p.Leu103Argfs*53) was detected. This study further expands the spectrum of the sequence variants reported in the WNT10B gene, which result in the split hand/foot malformation.

| S-EPMC5901503 | biostudies-literature

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

Project description: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.

| S-EPMC5423807 | biostudies-literature

Copy-number variants and candidate gene mutations in isolated split hand/foot malformation.

Project description:Split hand/foot malformation (SHFM) is a congenital limb deficiency with missing or shortened central digits. Some SHFM genes have been identified but the cause of many SHFM cases is unknown. We used single-nucleotide polymorphism (SNP) microarray analysis to detect copy-number variants (CNVs) in 25 SHFM cases without other birth defects from New York State (NYS), prioritized CNVs absent from population CNV databases, and validated these CNVs using quantitative real-time polymerase chain reaction (qPCR). We tested for the validated CNVs in seven cases from Iowa using qPCR, and also sequenced 36 SHFM candidate genes in all the subjects. Seven NYS cases had a potentially deleterious variant: two had a p.R225H or p.R225L mutation in TP63, one had a 17q25 microdeletion, one had a 10q24 microduplication and three had a 17p13.3 microduplication. In addition, one Iowa case had a de novo 10q24 microduplication. The 17q25 microdeletion has not been reported previously in SHFM and included two SHFM candidate genes (SUMO2 and GRB2), while the 10q24 and 17p13.3 CNVs had breakpoints within genomic regions that contained putative regulatory elements and a limb development gene. In SHFM pathogenesis, the microdeletion may cause haploinsufficiency of SHFM genes and/or deletion of their regulatory regions, and the microduplications could disrupt regulatory elements that control transcription of limb development genes.

| S-EPMC5612852 | biostudies-literature

17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD).

Project description:Split-hand/foot malformation with long-bone deficiency (SHFLD) is a relatively rare autosomal-dominant skeletal disorder, characterized by variable expressivity and incomplete penetrance. Although several chromosomal loci for SHFLD have been identified, the molecular basis and pathogenesis of most SHFLD cases are unknown. In this study we describe three unrelated kindreds, in which SHFLD segregated with distinct but overlapping duplications in 17p13.3, a region previously linked to SHFLD. In a large three-generation family, the disorder was found to segregate with a 254?kb microduplication; a second microduplication of 527?kb was identified in an affected female and her unaffected mother, and a 430?kb microduplication versus microtriplication was identified in three affected members of a multi-generational family. These findings, along with previously published data, suggest that one locus responsible for this form of SHFLD is located within a 173?kb overlapping critical region, and that the copy gains are incompletely penetrant.

| S-EPMC3198152 | biostudies-literature

4q32-q35 and 6q16-q22 are valuable candidate regions for split hand/foot malformation.

Project description:On the basis of the Human Cytogenetic Database, a computerized catalog of the clinical phenotypes associated with cytogenetically detectable human chromosome aberrations, we collected from the literature 102 cases with chromosomal aberrations and split hand/foot malformation or absent fingers/toes. Statistical analysis revealed a highly significant association (P<0.001) between the malformation and the chromosomal bands 4q32-q35, 5q15, 6q16-q22 and 7q11.2-q22 (SHFM1). Considering these findings, we suggest additional SHFM loci on chromosome 4q, 6q and probably 5q. The regions 4q and 6q have already been discussed in the literature as additional SHFM loci. We now show further evidence. In the proposed regions, there are interesting candidate genes such as, on 4q: HAND2, FGF2, LEF1 and BMPR1B; on 5q: MSX2, FLT4, PTX1 and PDLIM7; and on 6q: SNX3, GJA1, HEY2 and Tbx18.

| S-EPMC2986561 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data