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Supplementary material J Med Genet Supplemental figures and tables Table S1. Summary of the trio and single proband-based exome sequencing experiment. Sequencing Mean Percent Candidate Total NS/SS/I Family Individual output sequencing target de novo variantsa variantsa (in Gb) Depth (median) ≥ 10X SNV Trio 1 P1 dijex132 3,49 101.13 93.9 47848 14369 1 Mother dijex133 3,18 92.05 94.0 48178 14498 - Father dijex134 3,19 92.29 94.0 46912 14019 - Trio 2 P2 dijex135 3,23 93.38 94.0 48097 14526 1 Mother dijex136 3,63 105.11 94.4 48258 14480 - Father dijex137 3,32 96.19 94.0 47934 14657 - Trio 3 P3 dijex138 3,19 92.38 93.5 48365 14504 2 Mother dijex139 3 86.75 93.8 48229 14400 - Father dijex140 3,43 99.31 94.1 48035 14540 - Trio 4 P4 dijex141 3,42 98.89 94.5 47107 14126 2 Mother dijex142 3,69 106.78 94.4 47583 14365 - Father dijex143 3,38 97.81 94.3 48296 14667 - Trio 5 P5 dijex144 3,02 87.48 93.8 47648 14425 3 Mother dijex145 3,16 91.37 93.9 47284 14275 - Father dijex146 3,3 95.66 93.9 47964 14589 - Trio 6 P6 dijex147 3,51 101.74 94.1 48192 14568 3 Mother dijex148 3,15 91.20 93.8 48211 14638 - Father dijex149 3,11 90.12 93.8 47109 14178 - Trio 7 P7 dijex150 3,23 93.64 94.4 47648 14393 2 Mother dijex151 3,66 105.85 94.6 48040 14633 - Father dijex152 3,06 88.55 94.1 47950 14557 - Trio 8 P8 dijex153 3,18 91.99 94.0 48028 14633 4 Mother dijex154 3,42 99.05 94.0 48065 14472 - Father dijex155 3,43 99.40 94.0 48475 14635 - Trio 9 P9 dijex156 3,41 98.83 94.3 48682 14759 2 Mother dijex157 3,21 92.90 94.0 47604 14276 - Father dijex158 3,18 92.14 93.7 47682 14477 - Trio 10 P10 dijex159 2,85 82.49 93.6 47162 14193 1 Mother dijex160 3,02 87.53 93.7 47015 14266 - Father dijex161 3,66 105.82 94.0 47922 14530 - Trio 11 P11 dijex240 4,55 131.82 94.4 47777 14297 0 Mother dijex241 3,82 110.64 94.2 48415 14548 - Father dijex242 4,23 122.57 94.6 47923 14330 - Trio 12 P12 dijex244 2,9 84.10 93.7 47602 14441 2 Mother dijex245 3,44 99.63 94.1 47781 14564 - Father dijex246 2,85 82.45 93.7 48235 14841 - Trio 13 P13 dijex250 3,56 102.96 93.4 49688 15008 4 Mother dijex251 3,43 99.19 94.3 47888 14526 - Father dijex252 3,37 97.56 94.1 48549 14718 - Trio 14 P14 dijex253 3,02 87.49 93.8 47912 14322 3 Mother dijex254 4,27 123.50 94.6 48149 14513 - Father dijex255 3,12 90.42 94.0 48015 14327 - Trio 15 P15 dijex256 2,66 77.03 93.4 47958 14517 3 Mother dijex257 3,16 91.52 94.0 47898 14533 - Father dijex258 3,4 98.52 94.1 47962 14357 - 1 Chevarin M, et al. J Med Genet 2020;0:1–9. doi: 10.1136/jmedgenet-2019-106425 Supplementary material J Med Genet Trio 16 P16 dijex374 2,89 83.66 94.0 55874 16557 0 Mother dijex376 3,01 87.24 94.2 57333 17154 - Father dijex375 3,01 87.21 94.2 56358 16861 - Trio 17 P17 dijex380 3,03 87.59 94.2 48224 14622 1 Mother dijex382 3,31 95.79 94.3 48945 14852 - Father dijex381 3,19 92.31 94.3 49171 15121 - Trio 18 P18 dijex377 3,07 89.01 94.3 47841 14520 2 Mother dijex379 3,02 87.42 94.2 48018 14594 - Father dijex378 3,25 94.09 94.3 48139 14539 - Trio 19 P19 dijex397 2,78 80.48 93.4 48341 14717 3 Mother dijex399 3,34 96.68 93.9 49299 15038 - Father dijex398 3,88 112.28 94.3 49618 15164 - Trio 20 P20 dijex265 3,35 97.00 94.3 48951 14806 1 Mother dijex393 3,29 95.25 93.7 47506 14352 - Father dijex392 3,29 95.15 93.9 49258 14968 - Trio 21 P21 dijex272 2,94 85.04 93.8 48799 14735 1 Mother dijex395 2,63 76.23 93.1 47352 14327 - Father dijex394 3,15 91.21 93.7 47966 14509 - Trio 22 P22 dijex383 3,24 93.68 94.1 48134 14494 1 Mother dijex385 3,13 90.63 94.3 49245 14972 - Father dijex384 3,31 95.70 94.5 49344 15058 - Trio 23 P23 dijex412 2,24 64.81 92.5 50721 15564 1 Mother dijex413 2,19 63.49 91.9 50642 15781 - Father dijex414 2,60 75.14 94.0 50727 15345 - Trio 24 P24 dijex758 3,52 101.96 96.5 49726 15181 2 Mother dijex759 3,63 105.22 96.4 50321 15479 - Father dijex760 3,69 106.72 96.3 49637 15195 - Trio 25 P25 dijex761 3,54 102.52 96.2 49847 15187 2 Mother dijex762 3,02 87.40 95.3 50109 15319 - Father dijex763 3,56 103.04 95.3 49315 15146 - Trio 26 P26 dijex838 5,34 154.69 96.7 52024 15681 2 Mother dijex839 3,29 95.16 95.6 51028 15515 - Father dijex840 3,14 90.84 95.4 50760 15436 - Trio 27 P27 dijex841 3,29 95.16 94.3 50051 15336 0 Mother dijex842 3,39 98.24 91.1 50603 15684 - Father dijex843 2,86 82.76 94.1 50754 15641 - Trio 28 P28 dijex879 4,67 135.12 95.9 48101 14483 2 Mother dijex880 2,96 85.68 94.5 48318 14761 - Father dijex881 2,89 83.62 94.4 47376 14402 - Trio 29 P29 dijex882 3,14 90.80 94.7 48538 14924 4 Mother dijex884 3,34 96.55 94.5 48458 14837 - Father dijex883 2,73 78.94 94.4 48003 14708 - Trio 30 P30 dijex905 3,15 91.09 94.6 48744 14886 2 Mother dijex906 3,07 88.93 94.5 48592 14859 - Father dijex907 3,32 96.25 94.7 48866 14898 - Trio 31 P31 dijex908 3,73 107.96 95.0 48714 14914 3 Mother dijex909 3,33 96.33 94.9 48419 14945 - Father dijex910 3,32 96.20 94.7 47989 14625 - Trio 32 P32 dijex911 3,27 94.72 94.8 48169 14623 1 Mother dijex912 3,44 99.66 95.0 48409 14746 - Father dijex913 3,34 96.71 94.6 47853 14556 - Trio 33 P33 dijex1277 3,29 95.18 95.8 58552 17553 1 + CNV Mother dijex1315 2,88 83.32 95.7 59246 17930 - Father dijex1316 3,32 96.22 96.3 59522 17894 - 2 Chevarin M, et al. J Med Genet 2020;0:1–9. doi: 10.1136/jmedgenet-2019-106425 Supplementary material J Med Genet Solo 1 P34 dijex260 3,31 95.91 94.4 50938 15524 1 Solo 2 P35 dijex261 2,91 84.38 93.8 47796 14360 1 Solo 3 P36 dijex262 3,45 99.82 94.4 48560 14788 1 Solo 4 P37 dijex270 3,26 94.35 94.4 47250 14231 1 Solo 5 P38 dijex271 3,41 98.68 94.3 47740 14341 1 Solo 6 P39 dijex273 2,9 84.05 93.8 47212 14141 0 Solo 7 P40 dijex239 3,22 93.15 93.9 48447 14658 1 Solo 8 P41 dijex243 3,18 92.06 93.8 47813 14403 1 Solo 9 P42 dijex247 2,9 84.02 93.8 47995 14656 0 Solo 10 P43 dijex680 3,18 92.11 94.4 48882 14823 0 Solo 11 P44 dijex673 4,23 122.60 96.4 55694 16885 1 Solo 12 P45 dijex917 3,54 102.57 94.9 51197 15446 0 Solo 13 P46 dijex918 2,79 80.70 94.3 48151 14731 1 Solo 14 P47 dijex919 2,96 85.80 94.4 51849 15575 1 Solo 15 P48 dijex927 3,43 99.30 94.8 48267 14630 0 Solo 16 P49 dijex676 4,09 118.36 96.6 49411 15095 1 Solo 17 P50 dijex1278 3,61 104.42 96.1 49938 15168 0 Solo 18 P51 dijex1279 3,99 115.47 96.2 58548 17715 0 Solo 19 P52 dijex1292 3,91 113.10 96.3 49345 15119 1 Solo 20 P53 dijex1317 3,42 99.03 96.7 49705 14872 0 Solo 21 P54 dijex1383 4,68 135.44 96.9 50328 15152 0 Solo 22 P55 dijex1299 3,17 91.68 95.9 50286 15296 0 Solo 23 P56 dijex814 3,18 92.20 96.3 49657 15060 1 Solo 24 P57 dijex465 3,41 98.85 96.0 51337 15765 1 Solo 25 P58 dijex926 3,20 92,87 94,9 47414 14357 1 Solo 26 P59 dijex268 3,16 91.61 93.5 48320 14847 1 Solo 27 P60 dijex249 3,16 91.43 94.1 58020 17446 1 Solo 28 P61 dijex264 2,97 85.97 93.7 51780 15566 1 Solo 29 P62 dijex266 3,30 95.56 94.1 48566 14737 2 Solo 30 P63 dijex263 3,14 90.98 94.0 57077 17098 4 Solo 31 P64 dijex1509 3,36 97.48 96.6 60377 16569 1 Gb, gigabases; NS/SS/I, nonsynonymous changes, splice-site variants and insertions/deletions. aVariants that passed on the Genome Analysis Toolkit (GATK) hard-filtering parameters used for variant calling.
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  • Congenital Contractural Arachnodactyly; Two Unrelated Newborns with Novel Clinical Findings

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    Brief Report / Kısa Rapor Congenital Contractural Arachnodactyly; two unrelated newborns with novel clinical findings İbrahim Akalın1,2, Didem Armangil3, Esad Köklü3 1Trabzon Women’s and Children’s Hospital, ABSTRACT Genetic Diseases Diagnosis Center, Trabzon, Congenital Contractural Arachnodactyly (CCA; Beals syndrome) is a rare auto- Turkey. somal dominant disorder of connective tissue. CCA represents similar pheno- 2 Istanbul Medeniyet University, Goztepe typical features of Marfan syndrome such as tall stature and arachnodactyly, Training & Research Hospital, Medical Ge- with contrasting multiple joint contractures involving elbows, knees and even netics. İstanbul, Turkey fingers with typical crumpled ear helices. Here, we present two separate new- 3Trabzon Women’s and Children’s Hospital, borns representing novel findings such as retinal hemorrhage, bilateral sim- Neonatalogy Unit, Trabzon, Turkey. ian lines and cryptorchism in addition to classical findings. However, pedigree analyses of patients were suggesting somatic mosaicism in addition to the rep- resented distinct features of Beals syndrome; one with milder phenotype and even lack of typical crumpled ear helices, and the other with severe vertebral findings such as kyphoscoliosis. Key words: Beals syndrome, Marfan syndrome, arachnodactyly, retinal hemorrhage, kyphoscoliosis Eur J Basic Med Sci 2012;2(2):50-55 Received: 24.04.2012 Konjenital Kontraktürel Araknodaktili; yeni klinik bulgular içeren iki farklı yenidoğan olgu Accepted: 25.04.2012 ÖZET Congenital Contractural Arachnodactyly (CCA; Beals syndrome) otozomal rese- sif geçişli nadir bir bağ doku hastalığıdır. CCA, uzun boy ve araknodaktili gibi Marfan sendromundakine benzer klinik özellikler ile farklı olarak dirsek, diz ve hatta parmakları içeren çoklu eklem kontraktürleri ile tipik buruşuk kulak kepçesi görünümü sergiler. Biz bu yazımızda klasik bulgularına ek olarak reti- nal kanama, bilateral simian çizgiler ve kriptorşizm bulguları olan iki akraba olmayan yenidoğanı sunmaktayız.
  • Genetic Pathways Involved in Human Speech Disorders

    Genetic Pathways Involved in Human Speech Disorders

    Available online at www.sciencedirect.com ScienceDirect Genetic pathways involved in human speech disorders 1,2 1,3 Joery den Hoed and Simon E Fisher Rare genetic variants that disrupt speech development provide describe how next-generation sequencing and gene- entry points for deciphering the neurobiological foundations of driven studies are transforming this field, and argue that key human capacities. The value of this approach is illustrated emerging cell-based models of human brain development by FOXP2, a transcription factor gene that was implicated in will be crucial for a fuller understanding of how gene speech apraxia, and subsequently investigated using human disruptions yield speech disorders. cell-based systems and animal models. Advances in next- generation sequencing, coupled to de novo paradigms, Molecular perspectives on speech - the facilitated discovery of etiological variants in additional genes in example of FOXP2 speech disorder cohorts. As for other neurodevelopmental FOXP2 was the first gene for which rare variants could be syndromes, gene-driven studies show blurring of boundaries implicated in a monogenic speech disorder (primarily between diagnostic categories, with some risk genes shared characterized by childhood apraxia of speech; CAS; across speech disorders, intellectual disability and autism. Table 1). Since the initial report describing a causative Convergent evidence hints at involvement of regulatory genes point mutation in a multigenerational family, as well as a co-expressed in early human brain development, suggesting translocation disturbing the gene in an independent case that etiological pathways could be amenable for investigation in [3], different genetic disruptions of FOXP2 have been emerging neural models such as cerebral organoids.