Interstitial 1q25.3‐q31.3 deletion in a boy with mild manifestations

Abstract

We describe a 4-year-old boy with an accessory right thumb, short and broad toes, cryptorchidism, micrognathia, abnormally modeled ears, and delayed speech development. The chromosome analysis of patient's peripheral blood lymphocytes by conventional GTG banding demonstrated a small deletion in the long arm of chromosome 1. Confirmation and defined localization of the deleted segment to chromosomal bands 1q25.3-q31.3 was obtained by high resolution prometaphase analysis. Molecular studies, using a set of polymorphic chromosome 1q specific microsatellite markers, localized the deletion between the markers D1S2127 and D1S1727 on the paternally inherited chromosome 1. The maximum physical distance between these markers is approximately 21 Mb. The previously described two patients with 1q25-q31 deletions both had severe clinical manifestations, just as the other 10 patients with the proposed "intermediate 1q deletion syndrome," associated with 1q25-q32 deletions. Distinct from all these patients, the clinical picture of our patient is markedly milder, i.e., without growth retardation, microcephaly, or clear mental retardation.

Interstitial deletion of 1q42.13-q43 with Duane retraction syndrome

“…5 The deleted part of 1q observed in our patient is one of the smallest deletions in a type of distal interstitial deletion and it should be correlated with her mild phenotype. 5 The other previously described patients with larger 1q deletions including this region might have Duane syndrome, but there have been no reports about this phenotype.…”

“…5 Interstitial deletions of 1q have been mainly on a proximal portion of 1q such as q25-q31, but a distal interstitial deletion has not been clearly described or linked to any distinct features. 5 The deleted part of 1q observed in our patient is one of the smallest deletions in a type of distal interstitial deletion and it should be correlated with her mild phenotype. 5 The other previously described patients with larger 1q deletions including this region might have Duane syndrome, but there have been no reports about this phenotype.…”

1q25.2-q31.3 Deletion in a female with mental retardation, clinodactyly, minor facial anomalies but no growth retardation

“…Except for two cases reported by Hoglund and Milani [4,12], severe pre- and/or postnatal growth retardation was found in almost all of the patients with 1q25-q32 deletion. LHX4 (LIM homeobox gene 4) and CENPL (centromeric protein L) were suggested to be the primary candidate genes for growth retardation in the 1q25-q32 region.…”

“…Taken together, CENPL heterozygous deletion exhibited a full penetrance to growth retardation, while LHX4 deletion displayed an incomplete penetrance. Two patients with 1q25q32 deletion didn’t exhibit growth retardation [4,12], may due to the fact that their deleted regions encompassed neither LHX4 nor CENPL. Likewise, the normal growth in our patient was probably due to the fact that CENPL gene did not locate in the deleted region.…”

“…Based on the genotype-phenotype analysis, we proposed a critical region at 1q25.2 (chr1:174.5-177.6 Mb, build 36) with a length of 3.1 Mb may account for mental retardation. Eleven postnatal cases with 1q25-32 deletion containing the proposed critical region displayed apparent mental retardation (Figure 2), while two of the remaining three 1q25-32 deletions outside of the critical region exhibited mild mental retardation [4,12] and another case of neonate is absent from mental retardation [11]. Twenty-four genes located in the critical region, including 7 OMIM genes (ASTN1, RASAL2, ANGPTL1, FAM20B, TOR3A, ABL2, SOAT1).…”