Molecular mapping of a translocation breakpoint at 14q13 in a patient with mirror-image polydactyly of hands and feet

Matsumoto, Naomichi; Ohashi, Hirofumi; Kato, Rumiko; Fujimoto, Masahiro; Tsujita, Takahiro; Sasaki, Tohru; Nakano, Motoi; Miyoshi, Osamu; Fukushima, Yoshimitsu; Niikawa, Norio

doi:10.1007/s004390050387

Cited by 17 publications

(16 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A fluorescent in situ hybridization (FISH) analysis was performed using BAC clones mapped to chromosome 2 as probes to search for the 2p23.3 breakpoint-covering clones, as described previously (Matsumoto et al 1997b).…”

Section: Analysis Of Another Breakpoint At 2p233mentioning

confidence: 99%

“…1a) within the previously constructed 1.2-Mb bacterial artificial chromosome (BAC)/p1-derived artificial chromosome (PAC) contig (Matsumoto et al 1997b). To isolate CpG island-rich sequences, DNA from seven BAC/PAC clones (B319, B305, B368, P29, P7, P163, and P464) in the segment was double-digested with PstI/SacI, PstI/BssHII, or PstI/EagI, and the digests were subcloned into pBluescriptII SK(-) (Stratagene, La Jolla, CA USA).…”

Section: Methodsmentioning

confidence: 99%

“…Since his limb anomaly was associated with a de novo balanced chromosomal translocation, t(2;14)(p23.3;q13), we assumed that the translocation might have affected the function of a putative gene that might play a role in limb development (Matsumoto et al 1997a;b). We also had previously constructed a 1.2-Mb BAC/PAC contig covering the 14q13 breakpoint of the patient (Matsumoto et al 1997b). Here, we report on a novel gene that is disrupted at the 14q13 breakpoint.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A novel gene is disrupted at a 14q13 breakpoint of t(2;14) in a patient with mirror-image polydactyly of hands and feet

et al. 2002

Self Cite

View full text Add to dashboard Cite

Mirror-image polydactyly of hands and feet (MIP) is a very rare congenital anomaly characterized by mirror-image duplication of digits. To isolate the gene responsible for MIP, we performed translocation breakpoint cloning from an MIP patient with t(2;14)(p23.3;q13). We isolated a good candidate gene for MIP that was disrupted by the translocation of the patient. We had previously constructed a 1.2-megabase bacterial artificial chromosome (BAC)/P1-derived artificial chromosome (PAC) contig covering the 14q13 breakpoint of t(2;14)(p23.3;q13). From a 500-kb segment consisting of seven BAC/PAC clones in the contig, we isolated a novel gene (the mirror-image polydactyly 1 gene, designated as MIPOL1, GenBank Accession No. AY059470), in addition to the hepatocyte nuclear factor 3 alpha gene (HNF3A, GenBank Accession No. XM 007360). MIPOL1 spans about 350kb, comprises 15 exons, and encodes 442 amino acids. Northern blot analysis revealed that MIPOL1 expression is definite but very weak in adult heart, liver, skeletal muscle, kidney, and pancreas, and in fetal kidney. In view of the genome sequence and the contig map constructed, the 14q13 breakpoint of the patient was identified as located in intron 11 of MIPOL1, indicating that the gene was disrupted by the translocation, and that the breakage resulted in MIPOL1 protein truncation. Whole-mount in situ hybridization in mouse resulted in mouse Mipol1 signals all over E10.5-E13.5 mouse embryos. Two other unrelated patients with limb anomalies similar to MIP were subjected to mutation analysis of MIPOL1, but none had any mutations. We then isolated BAC clones from the other breakpoint, 2p23.3. A search for genes and expressed sequence tags in a more than 300-kb region around the 2p23.3 breakpoint found only the neuroblastoma-amplified protein gene (NAG, GenBank Accession No. NM 015909), which is located at least 50 kb centromeric to the breakpoint and is not likely to be related to MIP. MIPOL1 is a good candidate gene for the MIP type of anomaly.

show abstract

Section: Analysis Of Another Breakpoint At 2p233mentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel gene is disrupted at a 14q13 breakpoint of t(2;14) in a patient with mirror-image polydactyly of hands and feet

et al. 2002

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numerous examples are known of preaxial or mirror-image polydactyly with or without radial and/or tibial shortness [Lettice et al, 2003;Wechsler et al, 2004], and there likely is genetic heterogeneity [Vargas et al, 1995;Kim et al, 1997;Matsumoto et al, 1997;Borg et al, 1999;Kondoh et al, 2002]. The simultaneous presence of nasal clefts, short columella, hypoplastic alae nasi, or a crease in the philtrum is distinctive and would be diagnostic of LSS [Martínez-Frías et al, 1994].…”

Section: Discussionmentioning

confidence: 94%

Two patients with monomelic ulnar duplication with mirror hand polydactyly: Segmental Laurin–Sandrow syndrome

Innis

Hedera

2004

American J of Med Genetics Pt A

View full text Add to dashboard Cite

We have studied two unrelated boys with isolated left mirror hand and ulnar duplication. Neither had facial anomalies and family histories were unremarkable. We suggest that these boys have segmental Laurin-Sandrow syndrome, or mirror-image duplication, due to somatic mutation involving precursor cells of the left upper limb and that the facial and digital abnormalities in Laurin-Sandrow syndrome are consistent with ectopic anterior hedgehog signaling in the developing limb bud and in the maxillary processes of the face, which closely resemble findings in the Doublefoot (Dbf) mouse mutant.

show abstract

“…The gene for tetramelic mirror‐image polydactyly that is not related to LSS has been mapped to chromosome 14q13 [Kim et al, 1997; Matsumoto et al, 1997]. This may imply that mirror polydactyly is etiologically heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

Laurin-Sandrow syndrome with additional associated manifestations

Kantaputra

2001

Am. J. Med. Genet.

View full text Add to dashboard Cite

A Thai man with Laurin-Sandrow syndrome (LSS, MIM 135750), the ninth reported case, is described. He had an underdeveloped nasal bone, scar-like seams under the nose, large heads of mandibular condyles, and brachymesophalangy of toes as newly observed findings of the syndrome. He also had mental retardation. The patient had duplication of ulna, with triphalangeal thumbs, and polydactyly of one finger. The triphalangeal thumbs were non-opposable. Carpal bones were malformed. Mirror image polydactyly of the toes was present. There were nine toes on the right and eight on the left. Joint abnormalities were observed at his elbows, wrists, knees, ankles, fingers, and toes. Synostosis of severely malformed tarsal bones was noted. This appears to be the first case of LSS with anomalies not limited to the nose and limbs. The relationship between LSS, tibial hemimelia-polysyndactyly-triphalangeal thumbs syndrome, triphalangeal thumb-polysyndactyly syndrome, preaxial polydactyly types 2 and 3, and Haas-type syndactyly is discussed.

show abstract

Molecular mapping of a translocation breakpoint at 14q13 in a patient with mirror-image polydactyly of hands and feet

Cited by 17 publications

References 19 publications

A novel gene is disrupted at a 14q13 breakpoint of t(2;14) in a patient with mirror-image polydactyly of hands and feet

A novel gene is disrupted at a 14q13 breakpoint of t(2;14) in a patient with mirror-image polydactyly of hands and feet

Two patients with monomelic ulnar duplication with mirror hand polydactyly: Segmental Laurin–Sandrow syndrome

Laurin-Sandrow syndrome with additional associated manifestations

Contact Info

Product

Resources

About