Otopalatodigital syndrome type 2 in two siblings with a novel filamin A 629G>T mutation: Clinical, pathological, and molecular findings

Otopalatodigital syndrome type 2 (OPD2) is an uncommon X‐linked condition characterized by dysmorphic facies, a skeletal dysplasia affecting the axial and appendicular skeleton and extraskeletal anomalies including malformations of the brain, heart, genitourinary system, and intestines. Missense mut...

Full description

Saved in:
Bibliographic Details
Published in:American journal of medical genetics. Part A 2007-05, Vol.143A (10), p.1120-1125
Main Authors: Mariño‐Enríquez, Adrián, Lapunzina, Pablo, Robertson, Stephen P., Rodríguez, José I.
Format: Article
Language:English
Subjects:
Abnormalities, Multiple - genetics
Aborted Fetus
Amino Acid Sequence
Autopsy
Biological and medical sciences
Bone Diseases, Developmental - congenital
Bone Diseases, Developmental - genetics
Contractile Proteins - genetics
DNA Mutational Analysis
Ear Ossicles - abnormalities
Filamins
Fingers - abnormalities
FLNA gene
Genetic Diseases, X-Linked - diagnosis
Genetic Diseases, X-Linked - genetics
histopathology
Humans
Male
Medical genetics
Medical sciences
Microfilament Proteins - genetics
Molecular Sequence Data
neonatal autopsy
novel mutation
otopalatodigital syndrome type 2
Palate - abnormalities
pathology
Point Mutation
prenatal diagnosis
Sequence Homology, Amino Acid
Siblings
Syndrome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Otopalatodigital syndrome type 2 (OPD2) is an uncommon X‐linked condition characterized by dysmorphic facies, a skeletal dysplasia affecting the axial and appendicular skeleton and extraskeletal anomalies including malformations of the brain, heart, genitourinary system, and intestines. Missense mutations of the FLNA gene, which encodes for the protein filamin A, have recently been shown to cause OPD2 and the allelic syndromes otopalatodigital type 1, Melnick‐Needles, and frontometaphyseal dysplasia. Collectively these conditions constitute the otopalatodigital spectrum disorders. We report on two sibs affected by OPD2. The diagnosis was achieved at autopsy of a macerated male stillborn with typical external and skeletal findings of OPD2. A subsequent pregnancy was terminated due to ultrasonographic findings resembling those observed in the previous sibling. Histopathological studies revealed osseus sclerosis and do not support the previously reported membranous ossification defect observed in this condition. Mutation analysis demonstrated a novel mutation, 629G>T, in FLNA that had arisen de novo in the mother. This missense mutation predicts the substitution C210F within the second calponin homology domain of the actin‐binding domain of filamin A. The identical substitution has been recently identified in an analogous amino‐acid position within the actin binding domain of β‐spectrin leading to hereditary spherocytosis. The observation that phenylalanine is normally present in the same position in other proteins (utrophin, dystrophin) but leads to disease when present in filamin A implies that the function and/or structure of these actin binding domains are not entirely equivalent. © 2007 Wiley‐Liss, Inc.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.31696