The Phenotypic Spectrum of 16p11.2 Recurrent Chromosomal Rearrangements
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Clinical Descriptions
2.2.1. Patient 1
2.2.2. Patient 2
2.2.3. Patient 3
2.2.4. Patient 4
2.2.5. Patient 5
2.2.6. Patient 6
2.2.7. Patient 7
2.2.8. Patient 8
2.2.9. Patient 9
2.2.10. Patient 10
2.2.11. Patient 11
2.2.12. Patient 12
2.2.13. Patients 13 and 14
2.2.14. Patient 15
2.3. Methods
2.3.1. Isolation of Genomic DNA
2.3.2. Chromosomal Microarray Analysis—Array Comparative Genomic Hybridization
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient | Gender | Age at Diagnosis | Genotype/Size | Additional Findings | Breakpoints | Genes Included in the 16p11.2 Region | Clinical Summary |
---|---|---|---|---|---|---|---|
1 | F | 5 months | arr[GRCh37] 16p11.2(28629244–29031059) ×3 dn/402 Kb | arr[GRCh37] 1p36.33p36.22(564424–10892722) ×1dn/10.3 Mb | BP2–BP3 (Distal) | SULT1A1, EIF3C, EIF3CL, ATXN2L, TUFM, SH2B1, ATP2A1, RABEP2, CD19, NFATC2IP, SPNS1, LAT | Microcephaly, peculiar face, hypotonia, seizures since 1 month of age, brain MRI dysplastic right hemisphere with smaller dimensions, and pachygyria. At age 6 she does not walk and can only eat mashed foods |
2 | F | 1 year | arr[GRCh37] 16p11.2(28732295–28949619) ×1/220 Kb | BP2–BP3 (Distal) | ATXN2L, TUFM, SH2B1, ATP2A1, RABEP2, CD19, NFATC2IP, SPNS1, LAT | Microcephaly (3rd centile), psychomotor delay, brain MRI increased T2 signal and flair images | |
3 | M | 6 years | arr[GRCh37] 16p11.2(29652999–30198600) ×1/545 Kb | BP4–BP5 (Proximal) | SPN, QPRT, C16orf54, ZG16, KIF22, MAZ, PRRT2, C16orf53, MVP, CDIPT, LOC440356, SEZ6L2, ASPHD1, KCTD13, TMEM219, TAOK2, HIRIP3, INO80E, DOC2A, C16orf92, FAM57B, ALDOA, PPP4C, TBX6, YPEL3, GDPD3, MAPK3, LOC100271831, CORO1A | Flat forehead, flat face, deep-set eyes, cryptorchidism, hypotonia, psychomotor delay, obesity, and speech delay | |
4 | F | 6 months | arr[GRCh37] 16p11.2(29652999–30197341) ×3/545 Kb | arr[GRCh37] 9p24.3p24.1(204193–5162606) ×1/4.96 Mbarr[GRCh37] 10p15.3p12.31(136361–20023236) ×3/19.9 Mb | BP4–BP5 (Proximal) | Same as above | 36 cm occipitofrontal circumference, 52 cm length, deep-set eyes, seizures, sandal gap, heart U/S ventricular septal defect, enlarged left lateral abdomen. Prenatally hydronephrosis, renal cyst, and hypoglycemia |
5 | M | 15 years | arr[GRCh37] 16p11.2(29652999–30198600) ×1/545 Kb | BP4–BP5 (Proximal) | Same as above | Epilepsy, seizures, short stature, brachydactyly, scoliosis, normal OCF circumference, and learning difficulties | |
6 | M | 5 years | arr[GRCh37] 16p11.2(28824794–29031059) ×1/206 Kb | BP2–BP3 (Distal) | ATXN2L, TUFM, MIR4721, SH2B1, ATP2A1, ATP2A1-AS1, RABEP2, CD19, NFATC2IP, MIR4517, SPNS1, LAT | Profound speech delay, autism, stereotypic behavior, obsessions, and obesity | |
7 | M | 4 years | arr[GRCh37] 16p11.2(29592783–30190568) ×1/598 Kb | BP4–BP5 (Proximal) | SMG1P2, MIR3680-2, MIR3680-1, SPN, QPRT, C16orf54, ZG16, KIF22, MAZ, PRRT2, PAGR1, MVP, CDIPT, CDIPT-AS1, SEZ6L2, ASPHD1, KCTD13, TMEM219, TAOK2, HIRIP3, INO80E, DOC2A, C16orf92, FAM57B, ALDOA, PPP4C, TBX6, YPEL3, LOC101928595, GDPD3, MAPK3 | Macrocephaly, ID, IVF twin, hyperopia, hyperactivity, speech delay, neurodevelopmental disorder, autoimmune neutropenia, and allergies | |
8 | M | 4 years | arr[GRCh37] 16p11.2(28824794–29031059) ×1/206 Kb | BP2–BP3 (Distal) | ATXN2L, TUFM, MIR4721, SH2B1, ATP2A1, ATP2A1-AS1, RABEP2, CD19, NFATC2IP, MIR4517, SPNS1, LAT | Normal OCF circumference, psychomotor delay, and global developmental delay | |
9 | M | 3 years | arr[GRCh37] 16p11.2(28503803–29182196) ×1 pat/678 Kb | BP2–BP3 (Distal) | APOBR, IL27, NUPR1, SGF29, SULT1A2, SULT1A1, NPIPB8, EIF3C, EIF3CL, MIR6862-1, MIR6862-2, NPIPB9, ATXN2L, TUFM, MIR4721, SH2B1, ATP2A1, ATP2A1-AS1, RABEP2, CD19, NFATC2IP, MIR4517, SPNS1, LAT, RRN3P2 | Microcephaly, IUGR, speech delay, developmental delay, flat face, broad forehead, cryptorchidism, and hypospadias inherited from unaffected father | |
10 | M | 3 years | arr[GRCh37] 16p11.2(29572030–30106101) ×1/530 Kb | BP4–BP5 (Proximal) | SPN, QPRT, C16orf54, ZG16, KIF22, MAZ, PRRT2, PAGR1, MVP, CDIPT, CDIPTOSP, SEZ6L2, ASPHD1, KCTD13, TMEM219, TAOK2, HIRIP3, INO80E, DOC2A, C16orf92, TLCD3B, LOC112694756, ALDOA, PPP4C, TBX6, YPEL3, LOC101928595, GDPD3, MAPK3 | Microcephaly, round face, flat face, sparse eyebrows, strabismus, incident of seizures, developmental delay, iris coloboma, and optical nerve coloboma | |
11 | M | 1 year | arr[GRCh37] 16p11.2(28824794–29031059) ×1/206 Kb | BP2–BP3 (Distal) | ATXN2L, TUFM, MIR4721, SH2B1, ATP2A1, ATP2A1-AS1, RABEP2, CD19, NFATC2IP, MIR4517, SPNS1, LAT | Facial asymmetry, dysplastic ear, unilateral hearing loss, hyperopia, and developmental delay | |
12 | M | 7 years | arr[GRCh37] 16p11.2(29656684–30190568) ×1/534 Kb | BP4–BP5 (Proximal) | SPN, QPRT, C16orf54, ZG16, KIF22, MAZ, PRRT2, PAGR1, MVP, CDIPT, CDIPTOSP, SEZ6L2, ASPHD1, KCTD13, TMEM219, TAOK2, HIRIP3, INO80E, DOC2A, C16orf92, TLCD3B, LOC112694756, ALDOA, PPP4C, TBX6, YPEL3, LOC101928595, GDPD3, MAPK3 | Developmental delay, ASD, attending regular school with occasional additional help, and no dysmorphic features | |
13 | M | 4 years | arr[GRCh37] 16p11.2(29656684–30190568) ×1 mat/534 Kb | BP4–BP5 (Proximal) | Same as above | Profound speech delay, autism, stereotypic behavior, obsessions, and obesity inherited from unaffected mother | |
14 | M | 4 years | arr[GRCh37] 16p11.2(29656684–30190568) ×1 mat/534 Kb | BP4–BP5 (Proximal) | Same as above | Profound speech delay, autism, stereotypic behavior, obsessions, and obesity inherited from unaffected mother | |
15 | F | 13 years | arr[GRCh37] 16p11.2(29656684–30190568) ×1 mat/534 Kb | BP4–BP5 (Proximal) | Same as above | Intellectual disability, epilepsy, and autism inherited from unaffected mother |
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Mitrakos, A.K.; Kosma, K.; Makrythanasis, P.; Tzetis, M. The Phenotypic Spectrum of 16p11.2 Recurrent Chromosomal Rearrangements. Genes 2024, 15, 1053. https://doi.org/10.3390/genes15081053
Mitrakos AK, Kosma K, Makrythanasis P, Tzetis M. The Phenotypic Spectrum of 16p11.2 Recurrent Chromosomal Rearrangements. Genes. 2024; 15(8):1053. https://doi.org/10.3390/genes15081053
Chicago/Turabian StyleMitrakos, Anastasios K., Konstantina Kosma, Periklis Makrythanasis, and Maria Tzetis. 2024. "The Phenotypic Spectrum of 16p11.2 Recurrent Chromosomal Rearrangements" Genes 15, no. 8: 1053. https://doi.org/10.3390/genes15081053