A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome.
We report on a large family in which a novel X-linked recessive mental retardation (XLMR) syndrome comprising macrocephaly and ciliary dysfunction co-segregates with a frameshift mutation in the OFD1 gene. Mutations of OFD1 have been associated with oral-facial-digital type 1 syndrome (OFD1S) that is characterized by X-chromosomal dominant inheritance and lethality in males. In contrast, the carrier females of our family were clinically inconspicuous, and the affected males suffered from severe mental retardation, recurrent respiratory tract infections and macrocephaly. All but one of the affected males died from respiratory problems in infancy; and impaired ciliary motility was confirmed in the index patient by high-speed video microscopy examination of nasal epithelium. This family broadens the phenotypic spectrum of OFD1 mutations in an unexpected way and sheds light on the complexity of the underlying disease mechanisms.
Budny
Bartlomiej
B
Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany.
Chen
Wei
W
Omran
Heymut
H
Fliegauf
Manfred
M
Tzschach
Andreas
A
Wisniewska
Marzena
M
Jensen
Lars R
LR
Raynaud
Martine
M
Shoichet
Sarah A
SA
Badura
Magda
M
Lenzner
Steffen
S
Latos-Bielenska
Anna
A
Ropers
Hans-Hilger
HH
D000483:Alleles; D015152:Blotting, Northern; D002648:Child; D002874:Chromosome Mapping; D002925:Ciliary Motility Disorders / Q000235:genetics* / Q000473:pathology; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D018076:DNA, Complementary; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D013577:Syndrome
D018076:DNA, Complementary; C115130:OFD1 protein, human; D011506:Proteins