title: A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.
abstract: PDAC (also termed Matthew Wood) syndrome is a rare, autosomal recessive disorder characterized by pulmonary hypoplasia/aplasia, diaphragmatic defects, bilateral anophthalmia, and cardiac malformations. The disorder is caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. We describe six cases from four families of Hmong ancestry, seen over a 30 years period in California. These include: (i) consanguineous siblings with a combination of bilateral anophthalmia, diaphragmatic abnormalities, truncus arteriosus, and/or pulmonary agenesis/hypoplasia; (ii) a singleton fetus with bilateral anophthalmia, pulmonary agenesis, cardiac malformation, and renal hypoplasia; (iii) a sibling pair with a combination of antenatal contractures, camptodactyly, fused palpebral fissures, pulmonary agenesis, and/or truncus arteriosus; (iv) a fetus with bilateral anophthalmia, bushy eyebrows, pulmonary agenesis, heart malformation, and abnormal hand positioning. The phenotypic spectrum of PDAC syndrome has until now not included contractures or camptodactyly. Sequencing of STRA6 in unrelated members of families three and four identified a novel, shared homozygous splice site alteration (c.113 + 3_4delAA) that is predicted to be pathogenic. We hypothesize this may represent a unique disease allele in the Hmong. We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder.
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Julien L
authors.initials: JL
authors.lastname: Marcadier
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Mears
authors.affiliation: Community Perinatology Medical Group, Fresno, California.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Woods
authors.affiliation: Genetic Medicine Central California, Fresno, California.
authors.forename: Jamie
authors.initials: J
authors.lastname: Fisher
authors.affiliation: Community Perinatology Medical Group, Fresno, California.
authors.forename: Cory
authors.initials: C
authors.lastname: Airheart
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Wen
authors.initials: W
authors.lastname: Qin
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Chandree L
authors.initials: CL
authors.lastname: Beaulieu
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Dyment
authors.affiliation: Department of Medical Genetics and Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: A Micheil
authors.initials: AM
authors.lastname: Innes
authors.affiliation: Genetic Medicine Central California, Fresno, California.|Department of Pediatrics, University of California, San Francisco, California.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Curry
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D017398:Alternative Splicing / Q000235:genetics*; D000853:Anophthalmos / Q000235:genetics* / Q000473:pathology; D002140:California; D003241:Consanguinity; D003286:Contracture / Q000235:genetics* / Q000473:pathology; D005260:Female; D005865:Gestational Age; D006228:Hand Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D006330:Heart Defects, Congenital / Q000235:genetics / Q000473:pathology; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000002:abnormalities* / Q000473:pathology; D008171:Lung Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008850:Microphthalmos / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D011379:Prognosis; D013577:Syndrome
chemical_list: D008565:Membrane Proteins; C519685:STRA6 protein, human
keywords: Matthew-Wood syndrome; PDAC syndrome; STRA6; anophthalmia/microphthalmia; contractures