Segregation of a M404V mutation of the p62/sequestosome 1 (p62/SQSTM1) gene with polyostotic Paget's disease of bone in an Italian family

Table 1 Available clinical and mutational data on affected patients and gene carriers of PDB

Pedigree number (sex)	Age at clinical diagnosis or DNA evaluation; present age (years)	AP (U/l)	PDB-related clinical finding	Other relevant clinical data
II-3 (M)^a	Deceased	Unknown	Diffuse marked bone deformities (Fig. 2a)	Died at age 76 years from Alzheimer's disease
II-8 (F)^a	Deceased	Unknown	Bone deformities at both lower extremities	Died at age 52 years from colon-rectal cancer; also had breast cancer
II-10 (F)^a	Deceased	Unknown	Multiple marked diffuse skeletal deformities	Died at age 92 years from unknown cause
III-1 (F) ^b	57; 65	357	Third lumbar vertebra, pelvis, right proximal femur	Alive
III-3 (F) ^b	53; 79	560	Pelvis, both tibias	Alive. Apparently healthy
III-5 (M)^a	Not assessed	Unknown	Diffuse bone pain	Died at age 80 years from unknown cause
III-6 (F)^a	62; deceased	2,259	Right pelvis and proximal femur, IV and VIII left ribs	Died 12 years previously from osteogenic sarcoma on Pagetic bone (right pelvis)
III-12 (M) ^b	64; 82	380	Left hip^c	Alive. Benign prostate hyperplasia
III-13 (M) ^b	65; 83	610	T5, T10 and L4 vertebral bodies, sacrum, right tibia, right femur, right shoulder and collarbone	Alive. Allergy to pollen, hypertensive cardiopathy
IV-1 (F)	41	<120	None	Alive, age 42, healthy
IV-13 (F)	53	<120	None	Alive, hypertension, age 54
IV-14 (F)	41	<120	None	Alive, age 42, lumbar–sacral discal hernia, goitre
IV-15 (M)	47	<120	None	Alive, age 48 allergy to pollen
IV-16 (F)	48	<120	None	Alive, age 49, allergy to pollen

The M404V mutation was ascertained in individuals listed in bold. The highest observed levels of alkaline phosphatase (AP) are reported for each affected subject; the normal range is less than 120 units/l. PDB, Paget's disease of bone.
^aIndividuals strongly suspected to be potential PDB patients after careful reconstruction of the familial clinical history. ^bThese subjects received two treatment courses with oral risedronate (30 mg/day) for 3 months followed by a 112-day follow-up period without treatment [24]; complete normalization of serum AP levels and bone pain remission were observed in all these treated subjects. ^cTotal bone scintigraphy was not performed on this subject; the skeletal extent of PDB is on the basis of X-ray evaluations.

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