Bilateral Bicolored Irides With Hirschsprung's Disease

Liang, James C.; Juárez, Claudio P.; Goldberg, Morton F.

doi:10.1001/archopht.1983.01040010071011

Cited by 32 publications

(7 citation statements)

References 20 publications

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“…After an exhaustive literature search, we identified only three reports of HSCR patients with heterochromia iridum as the sole associated anomaly [41], [42]. No mutation screening had been done.…”

Section: Resultsmentioning

confidence: 99%

Genetic Analyses of a Three Generation Family Segregating Hirschsprung Disease and Iris Heterochromia

et al. 2013

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We present the genetic analyses conducted on a three-generation family (14 individuals) with three members affected with isolated-Hirschsprung disease (HSCR) and one with HSCR and heterochromia iridum (syndromic-HSCR), a phenotype reminiscent of Waardenburg-Shah syndrome (WS4). WS4 is characterized by pigmentary abnormalities of the skin, eyes and/or hair, sensorineural deafness and HSCR. None of the members had sensorineural deafness. The family was screened for copy number variations (CNVs) using Illumina-HumanOmni2.5-Beadchip and for coding sequence mutations in WS4 genes (EDN3, EDNRB, or SOX10) and in the main HSCR gene (RET). Confocal microscopy and immunoblotting were used to assess the functional impact of the mutations. A heterozygous A/G transition in EDNRB was identified in 4 affected and 3 unaffected individuals. While in EDNRB isoforms 1 and 2 (cellular receptor) the transition results in the abolishment of translation initiation (M1V), in isoform 3 (only in the cytosol) the replacement occurs at Met91 (M91V) and is predicted benign. Another heterozygous transition (c.-248G/A; -predicted to affect translation efficiency-) in the 5′-untranslated region of EDN3 (EDNRB ligand) was detected in all affected individuals but not in healthy carriers of the EDNRB mutation. Also, a de novo CNVs encompassing DACH1 was identified in the patient with heterochromia iridum and HSCRSince the EDNRB and EDN3 variants only coexist in affected individuals, HSCR could be due to the joint effect of mutations in genes of the same pathway. Iris heterochromia could be due to an independent genetic event and would account for the additional phenotype within the family.

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Section: Resultsmentioning

confidence: 99%

Genetic Analyses of a Three Generation Family Segregating Hirschsprung Disease and Iris Heterochromia

et al. 2013

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“…42 Mutations in RET also cause Hirschsprung disease (MIM 142623), in which hearing loss is sometime detected. 43,44 LRRC18 encodes a leucine rich repeat containing protein member 18. Mutations in a different family member, LRTOMT (also known as LRRC51 ; MIM 612414), have been implicated in non-syndromic hearing loss.…”

Section: Discussionmentioning

confidence: 99%

USH1K, a novel locus for type I Usher syndrome, maps to chromosome 10p11.21–q21.1

et al. 2012

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We ascertained two large Pakistani consanguineous families (PKDF231 and PKDF608) segregating profound hearing loss, vestibular dysfunction, and retinitis pigmentosa, the defining features of Usher syndrome type 1 (USH1). To date seven USH1 loci have been reported. Here, we map a novel locus, USH1K, on chromosome 10p11.21-q21.1. In family PKDF231 we performed a genome-wide linkage screen and found a region of homozygosity shared among the affected individual at chromosome 10p11.21-q21.1. Meiotic recombination events in family PKDF231 define a critical interval of 11.74 cM (20.20 Mb) bounded by markers D10S1780 (63.83 cM) and D10S546 (75.57 cM). Affected individuals of family PKDF608 were also homozygous for chromosome 10p11-21-q21.1 linked STR markers. Of the 85 genes within the linkage interval, PCDH15, GJD4, FZD4, RET, and LRRC18 were sequenced in both families, but no potential pathogenic mutation was identified. The USH1K locus overlaps the non-syndromic deafness locus DFNB33 raising the possibility that the two disorders may be caused by allelic mutations.

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“…HSCH has also been described in trisomy 21 [Knox and Bensel, 1972], and Smith-Lemli-Opitz type II [Patterson et al, 1983]. HSCH also occurs in numerous other abnormalities of the neural crest: Ondine's curse [Haddad et al, 1978]; bilateral bicolored irides [Liang et al, 1983]; cutaneous piebaldism, bicolored irides, and congenital deafness [Goldberg 1966]; Waardenburg syndrome [Branski et al, 1979;Omenn and McKusick, 1979]; and microcephaly and iris coloboma [Hurst et al, 1988]. Recently, a mutation in the endothelin B gene was reported in a consanguineous family with Waardenburg syndrome and HSCH inherited recessively [Attie et al, 1995].…”

Section: Discussionmentioning

confidence: 99%