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Hypoparathyroidism‐retardation‐dysmorphism syndrome in a girl: A new variant not caused by a TBCE mutation—clinical report and review
Author(s) -
Courtens Winnie,
Wuyts Wim,
Poot Martin,
Szuhai Karoly,
Wauters Jan,
Reyniers Edwin,
Eleveld Marc,
Diaz George,
Nöthen Markus M.,
Parvari Ruti
Publication year - 2006
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31122
Subject(s) - hypoparathyroidism , locus (genetics) , intellectual disability , genetics , facial dysmorphism , biology , gene , medicine , phenotype , endocrinology
Hypoparathyroidism‐retardation‐dysmorphism (HRD) or Sanjad–Sakati syndrome (SSS) (OMIM 241410) is a rare autosomal recessive (AR) inherited condition, characterized by congenital hypoparathyroidism (hypoPTH), retardation, seizures, and a typical facial dysmorphism, consisting of prominent forehead, deep‐set eyes, and abnormal external ears. This disorder has been mapped to the long arm of chromosome 1 (1q42‐q43) and mutations in the gene coding for tubulin‐specific chaperone E (TBCE) have been identified as the cause of the disease. Mutations in the same gene were also reported in patients with AR Kenny–Caffey syndrome (KCS). We report on a 4½‐year‐old girl with congenital hypoPTH, seizures, developmental delay, and a facial dysmorphism, compatible with HRD syndrome. Mutation analyses revealed no mutations in the TBCE gene. In addition, normal TBCE protein and alpha‐tubulin immunostaining were observed in a lymphoblastoid line derived from the patient, excluding the TBCE gene as the causative gene of the syndrome in this patient. A de novo microduplication of probe RP11‐262I1 on 4q35 in the proposita was detected by microarray analyses, but this could not be confirmed by additional studies. We review and discuss the clinical findings of our case and those of the other reported cases with SSS and AR KCS. We conclude that a second gene locus for this disorder seems probable and that 4q35 needs further evaluation as a candidate region. © 2006 Wiley‐Liss, Inc.