Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences

Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences

The Catalogue for Transmission Genetics in Arabs CTGA Database

Piezo-Type Mechanosensitive Ion Channel Component 2

Alternative Names autosomal recessive disorder of Distal PIEZO2 Arthrogryposis with Impaired Proprioception and Family with Sequence Similarity 38, Member B Touch (DAIPT). FAM38B Molecular Genetics Record Category The PIEZO2 gene is located on the short arm of Gene locus chromosome 18. It spans a length of 482 kb of DNA and its coding sequence is spread across 55 WHO-ICD exons. The protein product encoded by this gene N/A to gene loci has a molecular mass of 318 kDa and consists of 2752 amino acids. Several additional isoforms of Incidence per 100,000 Live Births the PIEZO2 protein exist due to alternatively N/A to gene loci spliced transcript variants. The gene is found to be overexpressed in the brain, spinal cord, pancreas, OMIM Number liver and lung. Heterozygous mutations in the 613629 PIEZO2 gene, including missense variants and deletions, have been linked to the disorders of Mode of Inheritance MWKS, DA3 and DA5. So far only one mutation N/A to gene loci (R2686C) has been identified in MWKS. Homozygous and compound heterozygous Gene Map Locus mutations in the gene associated with Distal 18p11.22-p11.21 Arthrogryposis, with Impaired Proprioception and Touch (DAIPT) mainly include nonsense variants Description and deletions that cause frameshift and premature The PIEZO2 gene encodes a large protein truncation, often resulting in a non-functioning containing 31 transmembrane domains. This protein PIEZO2 protein. is believed to function as part of the principal mechano-transduction cation channel and is Epidemiology in the Arab World therefore essential for the rapid adaptation of Saudi Arabia mechanically-activated currents in somatosensory Monies et al. (2017) reported the findings of 1000 neurons. It plays a key role in the detection of diagnostic panels and exomes carried out at a next mechanical stimulus and is also involved in the generation sequencing lab in Saudi Arabia. One response to said mechanical stimulus. It is hence patient, a 12-year-old female from a essential for perceiving the sensations of touch and consanguineous family, suffered from severe lower proprioception. limb weakness, progressive scoliosis and suspected SMA but did not have arthrogryposis. She also Mutations in the gene are associated with the 3 reported a family history of this phenotype. Using overlapping autosomal dominant conditions of whole exome sequencing, a homozygous mutation Marden-Walker Syndrome (MWKS), Distal (c.273_279del, p.A91fs) was identified in exon 3 of Arthrogryposis Type 3 (DA3) and Distal the patient’s PIEZO2 gene, associated with DAIPT. Arthrogryposis Type 5 (DA5). PIEZO2 gene Given the atypical presentation of the patient, this mutations have also been implicated in the

case helped in the phenotypic expansion of the FI, Alsonbul A, Al Tala S, Balkhy S, Bassiouni R, disorder. Alenizi AS, Hussein MH, Hassan S, Khalil M, Tabarki B, Alshahwan S, Oshi A, Sabr Y, References Alsaadoun S, Salih MA, Mohamed S, Sultana H, Monies D, Abouelhoda M, AlSayed M, Alhassnan Tamim A, El-Haj M, Alshahrani S, Bubshait DK, Z, Alotaibi M, Kayyali H, Al-Owain M, Shah A, Alfadhel M, Faquih T, El-Kalioby M, Subhani S, Rahbeeni Z, Al-Muhaizea MA, Alzaidan HI, Shah Z, Moghrabi N, Meyer BF, Alkuraya FS. The Cupler E, Bohlega S, Faqeih E, Faden M, Alyounes landscape of genetic diseases in Saudi Arabia based B, Jaroudi D, Goljan E, Elbardisy H, Akilan A, on the first 1000 diagnostic panels and exomes. Albar R, Aldhalaan H, Gulab S, Chedrawi A, Al Hum Genet. 2017 Aug;136(8):921-939. PMID: Saud BK, Kurdi W, Makhseed N, Alqasim T, El 28600779. Khashab HY, Al-Mousa H, Alhashem A, Kanaan I, Algoufi T, Alsaleem K, Basha TA, Al-Murshedi F, Related CTGA Records Khan S, Al-Kindy A, Alnemer M, Al-Hajjar S, Arthrogryposis, Distal, with Impaired Alyamani S, Aldhekri H, Al-Mehaidib A, Arnaout Proprioception and Touch (OMIM 617146) R, Dabbagh O, Shagrani M, Broering D, Tulbah M, Alqassmi A, Almugbel M, AlQuaiz M, Alsaman A, External Links Al-Thihli K, Sulaiman RA, Al-Dekhail W, Alsaegh http://www.genecards.org/cgi- A, Bashiri FA, Qari A, Alhomadi S, Alkuraya H, bin/carddisp.pl?gene=PIEZO2 Alsebayel M, Hamad MH, Szonyi L, Abaalkhail F, Al-Mayouf SM, Almojalli H, Alqadi KS, Elsiesy H, Contributors Shuaib TM, Seidahmed MZ, Abosoudah I, Akleh Sayeeda Hana H, AlGhonaium A, Alkharfy TM, Al Mutairi F, 19.09.2017 Eyaid W, Alshanbary A, Sheikh FR, Alsohaibani