title: A progeroid syndrome with neonatal presentation and long survival maps to 19p13.3p13.2.
abstract: We report on a Palestinian family with three affected individuals exhibiting progeroid syndrome characterized by intrauterine growth retardation, a progeroid appearance, failure to thrive, short stature, and hypotonia. The progeroid features were evident at birth. All the affected members of this family have survived beyond the neonatal period and one of them is currently a 27-year-old adult. As parental consanguinity suggested an autosomal recessive mode of inheritance, we employed homozygosity mapping using single nucleotide polymorphism arrays followed by next generation whole exome sequencing to identify the disease-causing gene. We were able to identify a single block of homozygosity shared between all the affected members of the studied family spanning 2.3 Mb on chromosome 19p13.3p13.2. However, Sanger sequencing of known genes and whole exome sequencing of the three affected sibs did not reveal a convincing causal mutation. These findings are anticipated to open the way for the identification of the molecular causes underlying this syndrome.
authors.affiliation: Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
authors.forename: Nadia
authors.initials: N
authors.lastname: Akawi
authors.forename: Bassam
authors.initials: B
authors.lastname: Ali
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al Gazali
mesh_terms: D000328:Adult; D002874:Chromosome Mapping / Q000379:methods; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome; D005190:Family; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000401:mortality; D005500:Follow-Up Studies; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D011371:Progeria / Q000235:genetics* / Q000401:mortality; D015996:Survival Rate
keywords: 19p13; Wiedemann-Rautenstrauch syndrome; exome sequencing; homozygosity mapping; linkage; neonatal; progeria; progeroid syndrome