title: A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations.
abstract: BACKGROUND
  The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance.
  
  
  RESULTS
  We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features.
  
  
  CONCLUSIONS
  We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.
authors.affiliation: Department of Neurology, Government Medical College, Thiruvananthapuram, Kerala, India. beenaiype@gmail.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Iype
authors.affiliation: Molecular Genetics, RILD Institute, University of Exeter, Royal Devon and Exeter NHS Hospital, Wonford, Exeter, UK. v.alakbarzade@exeter.ac.uk.|Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK. v.alakbarzade@exeter.ac.uk.
authors.forename: Vafa
authors.initials: V
authors.lastname: Alakbarzade
authors.affiliation: Department of Neurology, Government Medical College, Thiruvananthapuram, Kerala, India.
authors.forename: Mary
authors.initials: M
authors.lastname: Iype
authors.affiliation: Department of Anatomy and Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. drroyanasingh@gmail.com.
authors.forename: Royana
authors.initials: R
authors.lastname: Singh
authors.affiliation: Molecular Genetics, RILD Institute, University of Exeter, Royal Devon and Exeter NHS Hospital, Wonford, Exeter, UK.
authors.forename: Ajith
authors.initials: A
authors.lastname: Sreekantan-Nair
authors.affiliation: Molecular Genetics, RILD Institute, University of Exeter, Royal Devon and Exeter NHS Hospital, Wonford, Exeter, UK. B.Chioza@exeter.ac.uk.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Chioza
authors.affiliation: Department of Anatomy and Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. tmmohapatra2000@yahoo.com.
authors.forename: Tribhuvan M
authors.initials: TM
authors.lastname: Mohapatra
authors.affiliation: Molecular Genetics, RILD Institute, University of Exeter, Royal Devon and Exeter NHS Hospital, Wonford, Exeter, UK. E.Baple@exeter.ac.uk.|Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, UK. E.Baple@exeter.ac.uk.|Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK. E.Baple@exeter.ac.uk.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Baple
authors.affiliation: Molecular Genetics, RILD Institute, University of Exeter, Royal Devon and Exeter NHS Hospital, Wonford, Exeter, UK.|Southwest Thames Regional Genetics Centre, St George's Healthcare NHS Trust, London, SW17 0RE, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Patton
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Warner
authors.affiliation: Clinical Neuroscience, Royal Free Campus, UCL Institute of Neurology, London, UK. c.proukakis@ucl.ac.uk.
authors.forename: Christos
authors.initials: C
authors.lastname: Proukakis
authors.affiliation: Southwest Thames Regional Genetics Centre, St George's Healthcare NHS Trust, London, SW17 0RE, UK. Abhijit.Kulkarni@stgeorges.nhs.uk.
authors.forename: Abhi
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Molecular Genetics, RILD Institute, University of Exeter, Royal Devon and Exeter NHS Hospital, Wonford, Exeter, UK. a.h.crosby@exeter.ac.uk.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Crosby
mesh_terms: D025063:Chromosome Disorders / Q000209:etiology / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D002894:Chromosomes, Human, Pair 4; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007194:India; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D017384:Sequence Deletion; D014314:Trisomy; D054877:Wolf-Hirschhorn Syndrome / Q000235:genetics