OBJECTIVES: To perform a genotype-phenotype correlation study in an X-linked congenital idiopathic nystagmus pedigree (pedigree 1) and to assess the allelic variance of the FRMD7 gene in congenital idiopathic nystagmus. METHODS: Subjects from pedigree 1 underwent detailed clinical examination including nystagmology. Screening of FRMD7 was undertaken in pedigree 1 and in 37 other congenital idiopathic nystagmus probands and controls. Direct sequencing confirmed sequence changes. X-inactivation studies were performed in pedigree 1. RESULTS: The nystagmus phenotype was extremely variable in pedigree 1. We identified 2 FRMD7 mutations. However, 80% of X-linked families and 96% of simplex cases showed no mutations. X-inactivation studies demonstrated no clear causal link between skewing and variable penetrance. CONCLUSIONS: We confirm profound phenotypic variation in X-linked congenital idiopathic nystagmus pedigrees. We demonstrate that other congenital nystagmus genes exist besides FRMD7. We show that the role of X inactivation in variable penetrance is unclear in congenital idiopathic nystagmus. Clinical Relevance We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations. While FRMD7 mutations may be found in some cases of X-linked congenital idiopathic nystagmus, the diagnostic yield is low. X-inactivation assays are unhelpful as a test for carrier status for this disease.
OBJECTIVES: To perform a genotype-phenotype correlation study in an X-linked congenital idiopathic nystagmus pedigree (pedigree 1) and to assess the allelic variance of the FRMD7 gene in congenital idiopathic nystagmus. METHODS: Subjects from pedigree 1 underwent detailed clinical examination including nystagmology. Screening of FRMD7 was undertaken in pedigree 1 and in 37 other congenital idiopathic nystagmus probands and controls. Direct sequencing confirmed sequence changes. X-inactivation studies were performed in pedigree 1. RESULTS: The nystagmus phenotype was extremely variable in pedigree 1. We identified 2 FRMD7 mutations. However, 80% of X-linked families and 96% of simplex cases showed no mutations. X-inactivation studies demonstrated no clear causal link between skewing and variable penetrance. CONCLUSIONS: We confirm profound phenotypic variation in X-linked congenital idiopathic nystagmus pedigrees. We demonstrate that other congenital nystagmus genes exist besides FRMD7. We show that the role of X inactivation in variable penetrance is unclear in congenital idiopathic nystagmus. Clinical Relevance We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations. While FRMD7 mutations may be found in some cases of X-linked congenital idiopathic nystagmus, the diagnostic yield is low. X-inactivation assays are unhelpful as a test for carrier status for this disease.
Authors: Anna Hackett; Patrick S Tarpey; Andrea Licata; James Cox; Annabel Whibley; Jackie Boyle; Carolyn Rogers; John Grigg; Michael Partington; Roger E Stevenson; John Tolmie; John Rw Yates; Gillian Turner; Meredith Wilson; Andrew P Futreal; Mark Corbett; Marie Shaw; Jozef Gecz; F Lucy Raymond; Michael R Stratton; Charles E Schwartz; Fatima E Abidi Journal: Eur J Hum Genet Date: 2009-12-23 Impact factor: 4.246
Authors: Mervyn G Thomas; Moira Crosier; Susan Lindsay; Anil Kumar; Shery Thomas; Masasuke Araki; Chris J Talbot; Rebecca J McLean; Mylvaganam Surendran; Katie Taylor; Bart P Leroy; Anthony T Moore; David G Hunter; Richard W Hertle; Patrick Tarpey; Andrea Langmann; Susanne Lindner; Martina Brandner; Irene Gottlob Journal: Brain Date: 2011-02-08 Impact factor: 13.501
Authors: Anja K Mayer; Muhammad Mahajnah; Mervyn G Thomas; Yuval Cohen; Adib Habib; Martin Schulze; Gail D E Maconachie; Basamat AlMoallem; Elfride De Baere; Birgit Lorenz; Elias I Traboulsi; Susanne Kohl; Abdussalam Azem; Peter Bauer; Irene Gottlob; Rajech Sharkia; Bernd Wissinger Journal: Brain Date: 2019-06-01 Impact factor: 13.501