PURPOSE: Nail-Patella syndrome (MIM 161200) is a rare autosomal dominant disorder characterized by hypoplastic or absent patellae, dystrophic nails, dysplasia of the elbows, and iliac horn. In 40% of cases, a glomerular defect is present and, less frequently, ocular damage is observed. Inter- and intrafamilial variable expressivity of the clinical phenotype is a common finding. Mutations in the human LMX1B gene have been demonstrated to be responsible for Nail-Patella syndrome in around 80% of cases. METHODS: Standard polymerase chain reaction and sequencing methods were used for mutation and single nucleotide polymorphism identification and control of cloned sequences. Array-CGH (Agilent, 244A Kit) was used for detection of deletions. Standard cloning techniques and the Snapshot method were used for analysis of mosaicism. RESULTS: In this study, we present the results of LMX1B screening of 20 Nail-Patella syndrome patients. The molecular defect was found in 17 patients. We report five novel mutations and a approximately 2 Mb deletion in chromosome 9q encompassing the entire LMX1B gene in a patient with a complex phenotype. We present evidence of somatic mosaicism in unaffected parents in two cases, which, to our knowledge, are the first reported cases of inheritance of a mutated LMX1B allele in Nail-Patella syndrome patients from a mosaic parent. CONCLUSION: The study of the described case series provides some original observations in an "old" genetic disorder.
PURPOSE: Nail-Patella syndrome (MIM 161200) is a rare autosomal dominant disorder characterized by hypoplastic or absent patellae, dystrophic nails, dysplasia of the elbows, and iliac horn. In 40% of cases, a glomerular defect is present and, less frequently, ocular damage is observed. Inter- and intrafamilial variable expressivity of the clinical phenotype is a common finding. Mutations in the human LMX1B gene have been demonstrated to be responsible for Nail-Patella syndrome in around 80% of cases. METHODS: Standard polymerase chain reaction and sequencing methods were used for mutation and single nucleotide polymorphism identification and control of cloned sequences. Array-CGH (Agilent, 244A Kit) was used for detection of deletions. Standard cloning techniques and the Snapshot method were used for analysis of mosaicism. RESULTS: In this study, we present the results of LMX1B screening of 20 Nail-Patella syndrome patients. The molecular defect was found in 17 patients. We report five novel mutations and a approximately 2 Mb deletion in chromosome 9q encompassing the entire LMX1B gene in a patient with a complex phenotype. We present evidence of somatic mosaicism in unaffected parents in two cases, which, to our knowledge, are the first reported cases of inheritance of a mutated LMX1B allele in Nail-Patella syndrome patients from a mosaic parent. CONCLUSION: The study of the described case series provides some original observations in an "old" genetic disorder.
Authors: Olivia Boyer; Stéphanie Woerner; Fan Yang; Edward J Oakeley; Bolan Linghu; Olivier Gribouval; Marie-Josèphe Tête; José S Duca; Lloyd Klickstein; Amy J Damask; Joseph D Szustakowski; Françoise Heibel; Marie Matignon; Véronique Baudouin; François Chantrel; Jacqueline Champigneulle; Laurent Martin; Patrick Nitschké; Marie-Claire Gubler; Keith J Johnson; Salah-Dine Chibout; Corinne Antignac Journal: J Am Soc Nephrol Date: 2013-05-16 Impact factor: 10.121
Authors: Cindy G Boer; Konstantinos Hatzikotoulas; Lorraine Southam; Lilja Stefánsdóttir; Yanfei Zhang; Rodrigo Coutinho de Almeida; Tian T Wu; Jie Zheng; April Hartley; Maris Teder-Laving; Anne Heidi Skogholt; Chikashi Terao; Eleni Zengini; George Alexiadis; Andrei Barysenka; Gyda Bjornsdottir; Maiken E Gabrielsen; Arthur Gilly; Thorvaldur Ingvarsson; Marianne B Johnsen; Helgi Jonsson; Margreet Kloppenburg; Almut Luetge; Sigrun H Lund; Reedik Mägi; Massimo Mangino; Rob R G H H Nelissen; Manu Shivakumar; Julia Steinberg; Hiroshi Takuwa; Laurent F Thomas; Margo Tuerlings; George C Babis; Jason Pui Yin Cheung; Jae Hee Kang; Peter Kraft; Steven A Lietman; Dino Samartzis; P Eline Slagboom; Kari Stefansson; Unnur Thorsteinsdottir; Jonathan H Tobias; André G Uitterlinden; Bendik Winsvold; John-Anker Zwart; George Davey Smith; Pak Chung Sham; Gudmar Thorleifsson; Tom R Gaunt; Andrew P Morris; Ana M Valdes; Aspasia Tsezou; Kathryn S E Cheah; Shiro Ikegawa; Kristian Hveem; Tõnu Esko; J Mark Wilkinson; Ingrid Meulenbelt; Ming Ta Michael Lee; Joyce B J van Meurs; Unnur Styrkársdóttir; Eleftheria Zeggini Journal: Cell Date: 2021-08-26 Impact factor: 41.582