title: Microduplication of 7q36.3 encompassing the SHH long‑range regulator (ZRS) in a patient with triphalangeal thumb‑polysyndactyly syndrome and congenital heart disease.
abstract: Triphalangeal thumb‑polysyndactyly syndrome (TPT‑PS) is an autosomal dominant disorder with complete penetrance and a variable expression consisting of opposable triphalangeal thumbs, duplication of the distal thumb phalanx, pre‑axial polydactyly and duplication of the big toes (hallux). The causative gene of TPT‑PS has been mapped to 7q36.3. Sonic hedgehog (SHH) expressed in the zone of polarizing activity (ZPA) has an important role in defining the anterior‑posterior axis and numbers of digits in limb bud development. Point mutation or duplication in the ZPA regulatory sequence (ZRS), a cis‑regulator of SHH, will lead to TPT‑PS. The present study describes a 1‑year‑old female congenital heart disease (CHD) patient with TPT‑PS phenotype. In this Han Chinese family with TPT‑PS, high resolution single nucleotide polymorphism array technology identiﬁed a novel 0.29 Mb duplication comprising ZRS at 7q36.3 where LMBR1 is located. Additionally, a novel deletion of 22q11.21 was detected in the proband with Tetralogy of Fallot. However, the parents and other relatives of the patient did not harbor this genomic lesion nor CHD. The ﬁndings supported the hypothesis that an increased copy number variation of ZRS is the genetic mechanism underlying the phenotype of TPT‑PS, and corroborated that 22q11.21 deletion is a genetic cause of CHD.
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Ni
authors.initials: N
authors.lastname: Yin
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Lianghui
authors.initials: L
authors.lastname: Gong
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Bangliang
authors.initials: B
authors.lastname: Yin
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
mesh_terms: D002892:Chromosomes, Human, Pair 22; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D005260:Female; D020440:Gene Duplication / Q000235:genetics*; D006331:Heart Diseases / Q000150:complications / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D059785:Karyotype; D008342:Mandibulofacial Dysostosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D020825:T-Box Domain Proteins / Q000235:genetics
chemical_list: C485955:LMBR1 protein, human; D008565:Membrane Proteins; D020825:T-Box Domain Proteins; C108625:TBX1 protein, human; D004247:DNA