Autosomal and X-Linked Auditory Disorders - Genetics of Auditory Disorders - page 181

Pure tone audiometry characteristically demonstrates a progressive bilat-
eral symmetric sensorineural hearing loss predominantly affecting higher
frequencies in 80% of Stickler's syndrome patients (Herrmann et al. 1975;
Popkin and Polomeno 1974; Ruppert et al. 1970; Spallone 1987; Stickler
and Pugh 1967; Temple 1989; Zlotogora et al. 1992). Other auditory tests
indicate that the primary auditory pathology resides within the cochlea
(Griffith et al. 2000b; Jacobson et al. 1990; Szymko et al. 2000).

5.1.2 Genetics of Stickler Syndrome

Stickler syndrome is genetically heterogeneous and mutations have now
been identified in the genes encoding the a1, a2, and a3 subunits of type
XI collagen: COL11A1 , COL11A2 , and COL2A1 on chromosomes 6, 1, and
12, respectively (Tables 6.5, 6.6). The a3(XI) subunit is translated from
an alternatively spliced transcript of COL2A1 , which encodes the a1(II)

TABLE 6.6. Collagen types and their genes, chromosome map locations, and
associated disorders
Constituent

Type polypeptides Gene Chromosome Associated disorders

I a1(I) COL1A1 17q21.31-q22.05 Ehlers-Danlos syndrome, type VII

Osteogenesis imperfecta

a2(I) COL1A2 7q22.1 Ehlers-Danlos syndrome, type VII

Osteogenesis imperfecta

II a1(II) COL2A1 12q13.11-q13.2 Achondrogenesis

Hypochondrogenesis
Kniest dysplasia
Spondyloepimetaphyseal
dysplasia, Strudwick type
Spondyloepiphyseal dysplasia
congenita
Stickler syndrome, type I
Wagner syndrome

III a1(III) COL3A1 2q31 Ehlers-Danlos syndrome, type IV

Familial aortic aneurysms

IV a1(IV) COL4A1 13q34

a2(IV) COL4A2 13q34

a3(IV) COL4A3 2q36-q37 Alport syndrome (autosomal

recessive)

a4(IV) COL4A4 2q36-q37 Alport syndrome (autosomal

recessive)
Benign familial hematuria

a5(IV) COL4A5 Xq22 Alport syndrome (X-linked)

a6(IV) COL4A6 Xq22 Leiomyomatosis (in association

with X-linked
Alport syndrome as part of a
contiguous gene deletion
syndrome)