Is autosomal recessive deafness associated with oculocutaneous albinism a "coincidence syndrome"?
Hearing impairment is frequently found associated with pigmentary disorders in many syndromes. However, total oculocutaneous albinism (OCA) associated with deafness has been described only once, by Ziprkowski and Adam (Arch Dermatol 89:151-155, 1964) in an inbred family. A syndrome associating deafness and OCA was suggested by the authors, but two separate recessive genes segregating in this inbred group were also proposed later by Fraser (OMIM # 220900). Combined deafness and total OCA were also observed by us in a family originally reported to be nonconsanguineous but in which haplotyping showed evidence of a common ancestry: the proband was affected by both diseases, one of his sisters had only OCA and another sister had only deafness. Both the proband and his deaf sister were found to be homozygotes for the 35delG mutation (GJB2 gene), the most frequent cause of hereditary deafness. Linkage analysis with markers close to the four known OCA loci excluded linkage to OCA1, OCA2, and OCA3, and homozygosity in markers near OCA4 locus was observed. Sequencing of the corresponding gene (MATP) revealed a c.1121delT mutation, which leads to a stop codon at position 397 (L374fsX397). Clearly, the combined occurrence of deafness and albinism in this pedigree was due to mutations in two different genes, showing autosomal recessive inheritance. We speculate that the putative syndrome reported by Ziprkowski and Adam might have resulted from the co-occurrence of autosomal recessive deafness and albinism in the same pedigree, as suggested by Fraser.
Lezirovitz
Karina
K
Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, CP 11461, 05422-970, São Paulo, SP, Brazil.
Nicastro
Fernanda Stávale
FS
Divisão de Educação e Reabilitação de Distúrbios da Comunicação (DERDIC), Pontifícia Universidade Católica, São Paulo, Brazil.
Pardono
Eliete
E
Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, CP 11461, 05422-970, São Paulo, SP, Brazil.
Abreu-Silva
Ronaldo Serafim
RS
Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, CP 11461, 05422-970, São Paulo, SP, Brazil.
Batissoco
Ana Carla
AC
Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, CP 11461, 05422-970, São Paulo, SP, Brazil.
Neustein
Isaac
I
Departamento de Oftalmologia, Hospital Servidor Público Estadual SP, São Paulo, Brazil.
Spinelli
Mauro
M
Divisão de Educação e Reabilitação de Distúrbios da Comunicação (DERDIC), Pontifícia Universidade Católica, São Paulo, Brazil.
Mingroni-Netto
Regina Célia
RC
Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, CP 11461, 05422-970, São Paulo, SP, Brazil. renetto@ib.usp.br.
D000293:Adolescent; D016115:Albinism, Oculocutaneous / Q000150:complications* / Q000235:genetics; D000951:Antigens, Neoplasm; D001301:Audiometry, Pure-Tone; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis; D003638:Deafness / Q000150:complications* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D010375:Pedigree; D013577:Syndrome
D000951:Antigens, Neoplasm; D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C510061:SLC45A2 protein, human; D000072259:Connexin 26