title: A novel mutation in the C7orf11 gene causes nonphotosensitive trichothiodystrophy in a multiplex highly consanguineous kindred.
abstract: Trichothiodystrophy (TTD), also known as sulfur-deficient brittle hair syndrome, is a rare autosomal recessive multisystem disorder, which manifests with brittle hair, mental retardation, ichthyosis and decreased fertility. Mutations in the TTDN1 (C7orf11) gene have been shown to cause a nonphotosensitive type of trichothiodystrophy. We report of a 19 years old male, born to consanguineous parents of Arab-Muslim descent, who presented due to severe renal failure, but exhibited additional unique features, including developmental delay, mental retardation, splenomegaly, pancytopenia, hypogonadism and brittle hair. Following the clinical diagnosis of nonphotosensitive TTD, sequencing of the coding exons of C7orf11 was performed and revealed the patient to be homozygous for a novel c.505dupA mutation. As the severe renal failure following which the proband was referred to our care is not typically characteristic of this disorder, its significance is discussed. Molecular diagnosis of this highly affected family should enable genetic counseling and prenatal diagnosis for future pregnancies.
authors.affiliation: Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: ben_pode@hotmail.com.
authors.forename: Ben
authors.initials: B
authors.lastname: Pode-Shakked
authors.affiliation: Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Dina
authors.initials: D
authors.lastname: Marek-Yagel
authors.affiliation: Department of Dematology, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Shoshana
authors.initials: S
authors.lastname: Greenberger
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Naomi
authors.initials: N
authors.lastname: Pode-Shakked
authors.affiliation: The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
authors.affiliation: Department of Dematology, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Aviv
authors.initials: A
authors.lastname: Barzilai
authors.affiliation: Department of Internal Medicine C, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Saeed
authors.initials: S
authors.lastname: Yassin
authors.affiliation: Department of Internal Medicine C, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yechezkel
authors.initials: Y
authors.lastname: Sidi
authors.affiliation: Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Anikster
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D054463:Trichothiodystrophy Syndromes / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C519267:MPLKIP protein, human
keywords: Brittle hair; C7orf11; MPLKIP; TTD; TTDN1; Trichothiodystrophy