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GENATLAS PHENOTYPE

last update : 23-08-2010

Symbol	LRS1
Location	3p14.3
Name	Larsen syndrome 1
Corresponding gene	FLNB
Other symbol(s)	LAR1
Main clinical features	multiple dislocations of large joints, flattened facies, short fingernails, fingers anomalies( spatulate fingers) bilateral dislocation of the knees, pes cavus, cylindrically shaped fingers, and characteristic facies (wide-spaced eyes, flattened nasal bridge and prominent forehead, midface hypoplasia)
Genetic determination	autosomal dominant
Function/system disorder	osteo-articular
	congenital malformation
Type	disease

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments
missense		abnormal protein/gain of function	G1691S mutation mostly frequent

Remark(s)

clusters of mutations leading to substitutions in the actin-binding domain and filamin repeats 13-17 being the most common cause of Larsen increased F-actin binding affinity of the mutants presents a biochemical mechanism that differentiates the autosomal dominant gain-of-function FLNB disorders from those that arise through the complete loss of FLNB protein (Sawyer 2010)