SMAD4 Database

The mutation of family 20 has been previously reported as 189-197del (Woodford-Richens (2000), an in-frame deletion of nine bases in exon 1.12 This mutation has been further characterized as a most unusual and complex change, which comprises a net 1-bp deletion and 44-bp insertion. (2001)

Silent base change was previously undescribed.

2 cases of this specific mutation. General clinical features of patients with JPS given in TABLE 1 of Handra-Luca (2005). Specific information for each mutation is not given.

This mutation is predicted to abrogate the correct splicing of exons 2 and 3 of SMAD4 (although no mRNA was available to determine the precise effects)

Patient diagnosed in infancy, less than 5 juvenile polyps in the rectum and stomach

Male patient, age 12 - Showing signoid and rectal polyps (50+). Father had colon cancer, age 48. Uncle had colon cancer, age 50.

Originally reported as c.541C>T

c.668-?_1659+?del. Patient diagnosed with JPS at age 50, shows 2 colorectal polyps and over 200 gastric polyps

c.729_730insCCGC. Patient diagnosed at age 8, ~140 juvenile polyps in the colon and terminal ileum.

c.788-?_1659+?del. Patient diagnosed at age 12, has numerous colorectal polyps and 2 gastric polyps

A common polymorphism identified in many cases.

Patient clinically diagnosed.

Juvenile Polyposis Syndrome

Mutation causes JPS which predisposes patient to colorectal cancer. Patient in Gallione (2010) diagnosed with juvenile polyposis at age 6.5, family history reported for JP and HHT. Showed anemia and epistaxis, with no evidence of telangiectasia or digital clubbing. Patient also described as showing the sickle cell trait, a developmental venous anomaly in the right temporal lobe, and a right proximal tibia fibrous cortical defect. Additional References: Pyatt (2006), Aretz (2007), Gallione (2010)

General clinical features and mutation status for patients studied can be found in TABLE 1 of Sayed (2002). Specific information for each mutation is not given. Additional References: Calva-Cerqueira (2009), Howe (2004).

General clinical features and mutation status for patients studied can be found in TABLE 1 of Sayed (2002). Specific information for each mutation is not given. Howe (2004) describes 3 patients (ages 3, 5, and 9) from 1 family with juvenile polyps in the colon, osteoarthropathy, anaemia, and arteriovenous malformations (AVMs) of the lung or liver. One patient had a telangiectasia while another had a stroke. These patients were also diagnosed with HHT (ages 11, 7, and 8). Additional References: Calva-Cerqueira (2009), Gallione (2004).

Originally reported as c.1186A>C, p.Tyr353Ser. Mutation detected in two Finnish family members with juvenile polyps located in the large intestine. Patient 1 is described as having less then 10 polpys while patient 2 has between 10-50 polyps. Mutation was also found in an unaffected individual.

Patient diagnosed at age 14, juvenile polyps located in the stomach and colon. Patient in Gallione (2004) is described as having juvenile polyps in the stomach and colon causing anaemia at age 14, as well as telangiectasia and epistaxis indicative of HHT. Additional References: Calva-Cerqueira (2009), Howe (2004).

Patient described as having more than 20 juvenile polyps located throughout the colon and rectum. Patient in Aretz (2007) diagnosed with JPS at age 11, described as having more than 50 colorectal juvenile polyps. Addtitional References: Aretz (2007), Gallione (2010), and unpublished ARUP data.

De novo mutation, patient diagnosed with JPS at age 5, shows mulitple colorectal polyps

Patient diagnosed between ages 2 and 3, less than 15 juvenile polyps located in the colon. Patient in Gallione (2010) diagnosed with juvenile polyposis at age 2.5, family history reported. Polyps located in the cecum to rectum and in the sigmoid with AVMs in the lung and liver. The patient was diagnosed with JP/HHT and HHT both at the age of 5.5, family history of HHT reported. Additionally, the patient was described as showing epistaxis, digital clubbing, thrombosis, FTT, abdominal lower back and joint pain, and focal neruological symptoms (at the age 15).

Patient diagnosed at age 33, described as having many juvenile polyps in the colon and stomach

Patient diagnosed at age 30, less than 15 juvenile polyps (two with focal adenomatous changes) located in the colon. Additional Reference: Calva-Cerqueira (2009)

Patient clinically diagnosed.

Patient described as having many polyps located throughout the stomach, colon, and rectum. Additional References: Calva-Cerqueira (2009), Sayed (2002), Howe (2004)

Juvenile Polyposis Syndrome. Additional Reference: Calva-Cerqueira (2009).

General clinical features of patients with JPS given in TABLE 1 of Handra-Luca (2005). Specific clinical information related to each mutation is not given. Patient in Lamireau (2005), age 5, had clubbed fingers, anemia, and several juvenile polyps in the colon. Her brother, age 3, and father, age 35, also had marked clubbing and several juvenile polyps in the colon.

Most common mutation. Due to the nature of the sequence in this area, different descriptions of the nucleotide change have been reported: 2 cases Friedl (1999) [Originally reported as c.1372-1375delACAG, p.Asp415 frameshift], 3 cases Sayed (2002) [c.1244_1247delAGAC, p.Asp415 frameshift], 2 cases Pyatt (2006) [c.1242_1245delAGAC and c.1244_1247delACAG, both p.Asp415 frameshift], 6 cases Calva-Cerqueria (2009) [c.1244_1247delACAG, p.Asp415 frameshift], 1 case Roth (1999) [Orginally reported as c.1372_1375delAGAC, p.Asp415 frameshift], 4 cases Howe (2004) [1244_1247delAGAC, p.Asp415 frameshift], 4 cases Aretz (2007) [1245_1248delCAGA, p.Asp415 frameshift] 2 cases Friedl (2002) [c.1244_1247delACAG, p.Asp415 frameshift], 1 case Handra-Luca (2005) [c.1245_1248delCAGA, p.Asp415 frameshift], 1 case Pintiliciuc (2008) [1245_1248delCAGA, p.Asp415 frameshift], 1 case Patient diagnosed with juvenile polyposis at age 44, family history reported. Polyps located in the hepatic flexure and colon. Patient diagnosed with JP/HHT at age 50 with lung AVM (bilateral), telangiectasia, and epistaxis (Gallione 2010)[Orgininally reported as c.1242-1245delAGAC, p.Asp415 frameshift], 1 case unpublished ARUP data [c.1244_1247delACAG, p.Asp415 frameshift].

Male patient, age 39 with colonic polyps (tubular adenoma and adenoma); Female patient, age 6 with over 100 juvenile polyps, exocrine pancratic insuffieciency, short stature, development delay. Additional Reference: Handra-Luca (2005).

Juvenile Polyposis Syndrome. Additional Reference: Calva-Cerqueira (2009).

Juvenile Polyposis Syndrome

Patient shows several colorectal polyps and gastric polyps.

Mutation causes JPS which predisposes patient to colorectal cancer. Additional References: Pyatt (2006) and Aretz (2007).

Patient diagnosed at age 31, described as having juvenile polyps and tubular adenomas. Originally reported as 1524T>A, p.Trp508Arg. Additional Reference: Calva-Cerqueira (2009)

Juvenile Polyposis Syndrome. Additional Reference: Calva-Cerqueira (2009).

Patient shows numerous colorectal polyps and multiple gastric polyps

Male patient, >100 gastric juvenile polyps, 8 colorectal juvenile polyps

Juvenile Polyposis Syndrome

c.1587_88dupTA. Patiend diagnosed with juvenile polyposis at age 3, for reported family history. Polyps located in the colon and rectum with multiple AVMs in the lung and cerebral. Patient diagnosed with JP/HHT and HHT at ages 6 and 7 respectively, with no reported family history of HHT. Additionally, the patient showed anemia, telangiecetasia, epistaxis, digital clubbing, anemia, and asthma. Mutation was de novo.

Patient has telangiectases, epistaxis, colonic polyps, and arteriorvenous malformations in the lung and gastrointestinal tract.

Mutation causes JPS which predisposes patient to colorectal cancer. Additional References: Pyatt (2006), Aretz (2007).

Patient diagnosed with juvenile polyposis at age 36, family history not know. Polyps located in the colon and AVM in the lung. Patiend diagnosed with JP/HHT and HHT at age 36 and 7 respectively, family history reported for HHT. Additionally, the patient showed telangiecetasia, epistaxis, digital clubbing, and anemia.

General clinical features of patients with JPS given in TABLE 1 of Handra-Luca (2005). Specific clinical information related to each mutation is not given.