Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Autosomal recessive protein S deficiency

Autosomal recessive protein S deficiency is caused by mutations of the PROS1 gene. In contrast to the dominantly inherited form the mutations are not so severe such that a residual function may persist, and only if two alleles are affected a typical thrombophilia phenotype develops. Heterozygous carriers of those mutations usually have about 50% of the normal protein S activity.

Classification

Clinical chemistry allows to distinguish three types of protein S deficiency: Type 1: The protein is reduced in plasma. Type 2: The protein concentration in plasma is normal but its activity reduced. Type 3: The concentration of the free protein is reduced and this leads to a reduced plasma activity. Occasionally, a combination of type 3 and 1 or 2 can exist in one patient. The combination 1/3 is most common.[Error: Macro 'ref' doesn't exist]

Diagnosis

When measuring plasma concentration, warfarin and other vitamin K antagonists have to be discontinued sufficiently enough.

Systematic

Thromboembolic diseases
Autosomal dominant protein C deficiency
Autosomal dominant protein S deficiency
Autosomal recessive protein C deficiency
Autosomal recessive protein S deficiency
PROS1
F2
F5
Factor XII deficiency
HABP2
Hyperhomocysteinemic thrombosis
Hypoplasminogenemia
MTHFR
PAI transcription modulator
Protein Z deficiency
SERPINC1
THBD
Thrombophilia due to heparin cofactor 2 deficiency
VKORC1

References:

1.

Espinosa-Parrilla Y et al. (1999) Protein S gene analysis reveals the presence of a cosegregating mutation in most pedigrees with type I but not type III PS deficiency.

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2.

Pung-amritt P et al. (1999) Compound heterozygosity for one novel and one recurrent mutation in a Thai patient with severe protein S deficiency.

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3.

Mintz-Hittner HA et al. (1999) Vitreoretinal findings similar to retinopathy of prematurity in infants with compound heterozygous protein S deficiency.

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4.

Fischer D et al. (2010) Intracerebral mass bleeding in a term neonate: manifestation of hereditary protein S deficiency with a new mutation in the PROS1 gene.

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5.

Mahasandana C et al. (1990) Homozygous protein S deficiency in an infant with purpura fulminans.

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6.

Kamiya T et al. (1986) Inherited deficiency of protein S in a Japanese family with recurrent venous thrombosis: a study of three generations.

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7.

Comp PC et al. (1984) Familial protein S deficiency is associated with recurrent thrombosis.

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8.

Bosson JL et al. (1995) [Venous thromboembolic disease in children related to transient protein S deficiency following varicella].

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9.

OMIM.ORG article

Omim 614514 [^]
Update: April 29, 2019